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PILOT PROJECTS AWARDED 2021 (ROUND 2)

Title of Project: Prenatal Indoor Air Pollution Exposure and Maternal Asthma Health Among High Risk Obstetric Patients

Principal Investigator: Sonali Bose, MD, MPH

Co-Investigators: Angela Bianco, MD; Homero Harari, PhD; Rachel Meislin, MD

Project Period:  January 18, 2022– January 17, 2023

Pilot Award Amount: $50,000

 

Abstract: Poor asthma control during pregnancy is associated with significant adverse pregnancy complications for women, as well as an increased risk of post-natal respiratory disorders in their children. However, the influence of upstream environmental factors on maternal asthma morbidity have not been explored, and this knowledge is a critical foundation to improving maternal and child respiratory health. While indoor environmental exposures to fine particulate air pollution (PM2.5) have been demonstrated as a risk factor for poor asthma control in other populations, the impact of indoor air quality on maternal asthma morbidity during pregnancy is unknown. Our overarching hypothesis is that indoor exposure to fine particulate matter during pregnancy is associated with prenatal asthma morbidity, leading to adverse perinatal/ pediatric outcomes. We propose a feasibility pilot, in which we leverage our existing clinical collaboration between Mount Sinai OB-GYN and Respiratory Institute (RI) investigators to recruit an ethnically-diverse sample of pregnant patients and determine optimal methods to more comprehensively assess indoor PM2.5 and maternal asthma morbidity throughout gestation. To accomplish this, we will deploy indoor environmental monitors at repeated points in the pregnancy. In addition, we will integrate an existing clinical platform designed to remotely capture respiratory health data (currently being used at the RI to monitor post-COVID patients), including repeated validated asthma control questionnaires and spirometric lung function among pregnant mothers with active asthma. Identification of environmental determinants of increased asthma morbidity among urban pregnant women fills a significant gap in our understanding of factors contributing to poor perinatal outcomes within a vulnerable subpopulation. Data from this study will inform a larger longitudinal study powered to examine associations between a range of indoor pollutants/allergens and their mixtures and perinatal asthma-related complications, setting the stage for future interventions to mitigate pregnancy complications and transgenerational effects of maternal asthma on child respiratory health.


Title of Project: Air Pollution, Mitochondrial Heteroplasmy (MH), and Vaccine Efficacy in Children

Principal Investigator (MPI): Mike He PhD; Maayan Yitshak-Sade, PhD; Elena Colicino, PhD

Co-Investigators: Itai Kloog, PhD; Allan Just, PhD; Corina Lesseur, MD, PhD; Robert O. Wright, MD, MPH

Project Period: January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000

Abstract: The mitochondrion is one of the primary targets of oxidative stress to environmental exposure. Mitochondrial heteroplasmy (MH), the presence of subpopulations of mitochondria carrying mutations of their DNA sequence, is considered a marker of cumulative lifetime oxidative stress. The COVID-19 pandemic has generated rising interest in infectious disease epidemiology, and in particular questions about the role that air pollution plays in infectious disease transmission and vaccine effectiveness. Existing research has linked numerous environmental exposures to decreased effectiveness of routine prophylactic vaccinations, but no prior studies have assessed these associations with air pollution. We will link these three topics by studying the mitochondrial genome (mtDNA) and its direct association with fine particulate matter (PM2.5) as well as its indirection association in the epidemiologic pathway of PM2.5 and vaccine efficacy. We will include children in the ages of 4 to 5, enrolled in the Programming Research in Growth, Environment and Social Stress (PROGRESS) longitudinal birth cohort. Biosamples required for this proposal has already been collected through PROGRESS, making this study both time and cost-efficient. We will obtain PM2.5 predictions from satellite-based models with high spatial and temporal resolution. We will assess the association between prenatal and postnatal PM2.5 exposure and tetanus and diphtheria antibody concentrations or mitochondrial heteroplasmy. Finally, we will explore whether mitochondrial heteroplasmy mediates the association of PM2.5 and tetanus and diphtheria antibody concentrations. Data generated through this project will serve as the foundation for a future K99/R00 proposal that will investigate the effects of air pollution mixtures on MH frequency and vaccine antibody concentrations. The multi-PI team include a combination of early-stage and established investigators that provide a spectrum of expertise in exposure sciences, epidemiology, epi/genetics, toxicology, and biostatistics. The proposal uses both the Integrated Health Sciences Facility Core as well as the Biostatistics and Bioinformatics Facility Core.


Title of Project: Development of a novel retrospective biomarker of fluoride exposure using spatial mapping of teeth by laser induced breakdown spectroscopy (LIBS)

Principal Investigator (MPI): Mauro Martinez, PhD; Christine Austin, PhD

Co-Investigators: Manish Arora, BDS, MPH, PhD, FICD

Project Period: January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000

 

Abstract: Fluoride exposure has been associated with adverse health effects in the brain, kidney and other tissues. An important aspect to studying the health effects associated with fluoride exposure is capturing the timing of exposure. However, longitudinal measures of fluoride in traditional matrices is challenging. This project proposes a new method to quantify fluoride in teeth using laser induced breakdown spectroscopy (LIBS) that will reconstruct a history of early life fluoride exposure through quantitative mapping of fluoride in deciduous teeth. LIBS is an emission technique that measures fluoride in its atomic and molecular state, as calcium mono fluoride (CaF) that can be formed under the sampling environment. The quantification of fluoride requires a series of matrix-matched reference materials. As no such standard series is available commercially, we will use a new method to generate matrix-match standards of hydroxyapatite with known concentrations of fluoride. This new material will imitate teeth under laser ablation, enabling the optimization of LIBS acquisition parameters for high sensitivity and linearity at fluoride concentration ranges expected in teeth from individuals exposed to fluoridated and non-fluoridated water. We will validate this method within an animal model of fluoride exposure by testing the association between fluoride levels in teeth measured by LIBS and the fluoride dose, and by comparing LIBS values against that measured using an ion-selective electrode, an established technique that requires pulverization and acid digestion of the whole tooth. This method will develop a retrospective biomarker of fluoride exposure from the 2nd trimester to one year old at monthly intervals, and is minimally destructive so subsequent analysis can be performed on the same sample. This new biomarker will open a new perspective for future epidemiological studies to identify critical windows of early life fluoride exposure.


Title of Project: School Ventilation and SARS-CoV-2 Test Positivity: A Community-Based Study

Principal Investigator (MPI): Nicholas DeFelice, PhD; Maida Galvez, MD, MPH

Co-I: Laura McGuinn, PhD; Rachel Vreeman, MD, MS; Alison Lee, MD, MS, Chris Gennings, PhD, Nicole Bouvier, MD; Efrain Guerrero

Project Period: January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000

 

Abstract: During the COVID-19 pandemic, governments have implemented a range of public health measures including school closures to slow the spread of SARS-CoV-2. While the direct risk of COVID-19 infection in children is lower relative to the adult population, the indirect harms of the pandemic are substantial. School closures, in particular, can have immediate and long-lasting impacts on child development. In New York City (NYC), the calculated magnitude of student-level learning losses due to COVID-19 and the transition away from classroom-based instruction was on average 125 (69%) and 212 (118%) days of reading and math, respectively, relative to a typical 180-day school year. Opening schools to in-person learning is an important step in re-opening the economy; however, it comes with the risk of increasing contact networks. Together with our community partner, KIPP New York City public schools, we will explore the increased potential for transmission due to in-person schooling, by building statistical models where we will characterize (1) built environment profiles for each school and (2) mitigation measures for in-person schooling, and also explore associations with burden of COVID-19. We will collect data on school-level ventilation and additional mitigation strategies that were implemented within KIPP NYC and NYC schools, and relate these strategies to infection monitoring data. Finally, we will assess parents support of school-level mitigation strategies and whether this differs by certain demographic factors. Our ultimate goal is to identify cost effective and optimal environmental strategies to minimize transmission potential due to in-person schooling, and recommend robust, effective risk mitigation interventions to prevent the spread of SARS-CoV-2 and other respritory diseases. The findings from this pilot study will be used in multiple NIH grant applications, including R01s and K25 awards.


Title of Project: Association between Air Pollution, Stress, and Sleep Efficiency in 6 -7-year-old Children living in East Harlem

Principal Investigator (MPI): Terry Thompson, DHA, MPH; Maida Galvez, MD, MPH

Co-Investigators: Robert O. Wright, MD, MPH; Sarah Evans, PHD, MPH; Leon Hsu, ScD; Ray Lopez, BA; Luz Guel, BA, BS

Period: January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000

 

Abstract: Environmental toxicants, broadly defined to encompass chemical and non-chemical risk factors, present in the built environment, can adversely impact children’s growth and development. Children are particularly vulnerable to environmental exposures because of the sensitive nature of children’s neurodevelopment, a prenatal life stage marked by cell differentiation. Recently Bose et al. found an association between prenatal PM2.5 exposure and poorer sleep outcomes (i.e., sleep quantity and quality) in childhood. Yet, little is known about the relationship between air quality and sleep efficiency among children, within the larger context of household and psychosocial conditions. To address this knowledge gap, this pilot research study will examine potential relationships between indoor air quality and its effects on sleep patterns among twenty-five Hispanic children, 6-7 years old living in East Harlem. Aims are: 1) Engage with the Community Advisory Board (CAB) to assess environmental factors that may affect neighborhood air quality and child sleep in East Harlem via study design, and implementation of home and child appropriate healthy resources to assess caregiver understanding and perception of air pollution and household environmental risk factors that may affect child sleep. 2) Quantify associations between household PM2.5 exposure and sleep quantity and quality using indoor air monitors, continuous actigraphy, and a validated sleep questionnaire. 3) Working closely with the CAB, create reports for study participants outlining individual and aggregate study findings and steps they can take to improve air quality and child sleep. Reports will be tailored to the community needs and health literacy levels and educational resources adapted from existing materials from the Mount Sinai Pediatric Environmental Health Specialty Unit and the Institute for Exposomics Research. We will apply Community Advisory Board (CAB) involvement and community-partnered approaches throughout all stages of this study to ensure the needs of the study population are met.


Title of Project: The Impact of Prenatal Pesticide Exposure on Child Respiratory Outcomes in Mexico City

Principal Investigator: Cecilia Alcala, PhD, MPH; Maria Jose Rosa, DrPH

Co-Investigators: Syam Andra, PhD; Shelley Liu, PhD; Robert O. Wright, MD, MPH

Project Period:  January 18, 2022– January 17, 2023

Pilot Award Amount: $25,000

 

Abstract: In utero exposure to pesticides may adversely affect the developing respiratory system. There is limited assessment of prenatal pesticide exposure in urban settings particularly in Latin America and their association with adverse respiratory outcomes remains understudied. Sex differences have also been observed when exploring the effects of pesticide exposure. However, research on sex differences in the association between prenatal pesticide exposure and adverse respiratory outcomes is lacking. Thus, we aim to leverage the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort in Mexico to assess in utero pesticide exposure to organophosphate insecticides, and to evaluate their association with childhood lung function, and respiratory and atopic disease in childhood. We will analyze spot urine samples that were collected during the second trimester of pregnancy for dialkyl phosphates specific organophosphorus pesticide metabolites. Pulmonary function was assessed through spirometry (pre and post bronchodilator) and asthma, wheezing, and atopic disease was measured via the validated Spanish version of the International Study of Asthma and Allergies in Childhood survey (ISAAC). We hypothesize that higher prenatal pesticide exposure will be associated with adverse pulmonary function and asthma, wheezing, atopic disease, and sex differences will be observed.


Title of Project: Effect of Electronic Cigarette During Pregnancy on Maternal Urinary Metabolomics and the Neonatal Meconium Microbiome Related to Glucose Metabolism

Principal Investigator: Kirtan Kaur, PhD, MS, MPhil; Jia Chen, ScD

Co-Investigators: Lauren Petrick, PhD; Jianzhong Hu, PhD; Corina Lesseur, MD, PhD; Laura Stroud, PhD

Project Period:  January 18, 2022– January 17, 2023

Pilot Award Amount: $20,000

 

Abstract: Electronic cigarette (e-cig) use is on the rise and viewed as a safer alternative to regular cigarettes. Pregnant women are amongst those who often hold this view and have been documented to use e-cigs during pregnancy. There are limited studies exploring the effects of e-cig use on health outcomes, in particular among pregnant women. E-cig liquids are formulated with sugar alcohol bases, additives and flavorings (i.e., propylene glycol, vegetable glycerin) that can adversely impact glucose metabolism, which can be more detrimental to the dynamic maternal metabolism during pregnancy and to her developing fetus. This pioneering pilot study will assess how e-cig use during pregnancy impacts glucose homeostasis using urinary metabolomic analysis as well as the initial neonatal gut microbiome. An additional exploratory aim will examine whether birth outcomes (i.e., gestational age, birthweight) are associated with e-cig-related changes in metabolites and specific microbial profiles related to glucose metabolism. We will take advantage of a newly established birth cohort study focusing on the effects of maternal smoking behaviors during pregnancy and postnatal health outcomes. Maternal urine samples are collected in the second and third trimesters and neonate meconium is collected at birth. The urinary metabolome will be assayed with LC-MS and the meconium microbiome assessed by 16S rRNA sequencing. A targeted statistical pipeline will be used to focus the analysis on metabolites and microbe species relevant to glucose metabolism and insulin resistance. Lastly, birth outcome data will be gathered and assessed for correlations with the e-cig-related changes in the maternal urinary metabolome and neonatal meconium microbiome. Understanding how prenatal e-cig use can impact maternal metabolism and the initial neonatal microbiome and may subsequently bias both towards dysregulated glucose metabolism is important to evaluating e-cig safety.

PILOT PROJECTS AWARDED 2021 (ROUND 1)

Title of Project: Prospective omics study of risk factors associated with thyroid cancer

Principal Investigator (MPI): Maaike van Gerwen, MD, PhD; Lauren Petrick, PhD

Co-Investigators: Shyamalee Dassanayake, PhD; Seunghee Kim-Schulze, PhD; Elena Colicino, PhD; Eric Genden, MD

Project Period: July 27, 2021– July 26, 2022

Pilot Award Amount: $69,972

Abstract: Thyroid cancer (TC) incidence has been steadily increasing and has nearly tripled since the 1970’s in the US and worldwide. Early detection of small, papillary TCs using high quality diagnostic imaging explains only part of this increased incidence, and multiple studies have highlighted the potential contribution of exposure to environmental pollutants to this phenomenon. However, besides radiation, a well-established risk factor for TC, the environmental contributors to TC have yet to be identified. Endocrine disrupting chemicals (EDCs) are one class of compounds that are ubiquitously present and persistent in our environment, and are known to disrupt thyroid function. Data on their potentially carcinogenic effect on the thyroid gland is currently limited. We therefore propose to investigate EDCs [per-/polyfluoroalkyl substances (PFCs), diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their metabolites], as well as endogenous metabolites as potential risk factors associated with the increasing TC incidence (aim 1 and 2), using a nested case-control study (92 TC cases and 92 matched healthy controls). We will also measure proteins to explore potential causal pathways (aim 3). This is the first prospective study to investigate the association between exposure to persistent EDCs and TC on plasma samples collected pre-TC diagnosis using metabolomics and proteomics. The goal is to expand and include an explication set through our collaboration with the European Prospective Investigation into Cancer and Nutrition (EPIC) network in the Netherlands to generate data on exposure, metabolism and biologic response prior to onset of clinical symptoms or diagnosis. This will provide insights into TC etiology with the ultimate goal of identifying actionable risk factors for prevention efforts.


Title of Project: Characterizing the heat stress exposome to assess acute kidney injury in NYC runners

Principal Investigator (MPI): Nicholas DeFelice, PhD; Homero Harari, PhD

Co-Investigators: Alison Sanders, PhD; Chris Gennings, PhD; Steven Coca, DO, MS

Project Period: July 27, 2021– July 26, 2022

Pilot Award Amount: $25,000

 

Abstract: Heat stress occurs when the body’s ability to regulate internal temperature begins to fail, which may result from intense physical exertion (exercise-induced or occupational), shifts in environmental conditions, (i.e., temperature and humidity) or a combination of these factors. Chronic and repeated acute heat stress exposures can result in damage to the kidneys and other systems further priming an aberrant sequelae of subsequent acute kidney injury (AKI) and chronic disease. Yet, population-based methods to assess heat stress exposure (including internal body temperature, sweat rate, heart rate variability, minute ventilation, etc) and subsequent kidney function changes in real-time are limited. In this pilot study, we will assess acute recurrent heat stress exposures in a cohort of long distance runners to better understand how metabolic heat and ambient temperature impact kidney function. We will assess whether subclinical recurring kidney injury occurs among runners participating in intensive outdoor training, and are environmental conditions associated. This is important as recurrent AKI is a strong risk factor for early onset kidney disease. During the summer of 2021, 24 athletes (12 men, 12 women) will be solicited to run two loops of Central Park (21km half-marathon) three times (total 63 km), with 7 days between each run. Before each run, we will provide several environmental sensors on the athlete to capture individual-level exposures of ambient temperature, humidity, internal core temperature, volume loss, sodium loss, minute ventilation, heart rate variability and air pollution. Additionally, after each run, we will collect plasma and urine to analyze traditional and novel renal biomarkers. Using a within-host state-space model to evaluate individual exposure profiles, we will develop a heat stress exposure index to assess changes in subclinical renal biomarkers. Importantly, our pilot methodologies developed herein for heat stress assessment will be broadly applicable to future environmental and occupational exposure assessment scenarios.


Title of Project: Use of deciduous teeth to link trimester-specific exposures to PFAS and other chemical mixtures with biological response and neurodevelopment outcomes in children

Principal Investigator (MPI): Syam Andra, PhD; Christine Austin, PhD

Co-I: Paul Curtin, PhD; Heather Volk, MPH, PhD

Project Period: July 27, 2021– July 26, 2022

Pilot Award Amount: $25,000

 

Abstract: With increasing use of over 1,000 perfluoroalkyl substances (PFASs) across the US, exposure during the vulnerable prenatal period is expected. In addition, PFASs exposures during this critical period will coincide with co-exposures to other environmental chemicals. However, research to explore the prevalence of PFASs exposure, and co-exposure with other environmental chemicals, during this critical development period, and the downstream health effects and biological response to such exposures is lacking due to a dearth of available biomarkers. Shed deciduous teeth can be collected non-invasively and when sampled carefully, can reconstruct a child’s longitudinal exposure profile during the pre- and early postnatal period. We propose to develop a method to measure PFASs exposure at trimester resolution using shed deciduous teeth. In addition, we will develop a LC-MS/MS method using a single tooth extract for the simultaneous analysis of multiple biomarkers of exposure to environmental chemicals and biological response to exposure. We will conduct our study in a subset of children (n=100) from the Autism Spectrum Disorder Enriched Risk (ASD-ER) cohort, run out of Drexel University, PA. Teeth were collected for an Environmental Influences on Child Health Outcomes (ECHO) grant to test if early life exposure to persistent organic pollutants (POPs) such as pesticides and polychlorinated biphenyls, increase the risk of developing ASD. This project will enable us to expand the classes of POPs that can be measured in teeth, moving us closer to characterizing the tooth exposome and expanding the utility of teeth as a tool to study the health effects associated with early life environmental exposures. Findings will support a planned R21 submission that aims to leverage the data-rich tooth resource to advance the knowledge about the extent of early life exposure to classical and emerging PFASs, interaction with chemical mixtures, resulting biological response, and their association with child development.


Title of Project: Illuminating the “dark matter” of the exposome using a novel analytical workflow

Principal Investigator (MPI): Anna R. Robuck, PhD; Douglas Walker, PhD

Co-Investigators: N/A

Period: July 27, 2021– July 26, 2022

Pilot Award Amount: $25,000

 

Abstract: Recent advances in exposomic approaches that use untargeted high resolution mass spectrometry (UHRMS) provide critical advances for incorporating the exposome into precision medicine, risk assessment, and environmental health research. However, a substantial portion of the exposome remains unexplored or undefined, referred to as the “dark matter” of the exposome. This gap is a significant limitation that prevents the identification key exposures and effects underlying environment related diseases. We propose to address this research gap by developing an innovative exposomic workflow that combines bulk organic halogen and untargeted UHRMS measurements. Bulk halogen analysis enables quantitative measurement of total extractable organic halogens (EOX), providing a summary measure that can be used to estimate the overall exposure burden from chlorine, bromine, iodine and fluorine containing organic chemicals. We will optimize EOX measures for the exposome using a combination of instrumental neutron activation analysis (INAA) and combustion ion chromatography (CIC), in addition to UHRMS. Application of EOX techniques to environmental samples supports their high-sensitivity for detecting low level halogenated compounds at parts-per-billion concentrations; however, these methods have not been combined within an exposome workflow that will enable, for the first time, assessment of the total halogen burden within human populations. Our novel workflow will provide high-impact information quantitatively characterizing the missing fractions of the exposome, and provide a strategy for benchmarking coverage by UHRMS analytical and data handling analytical platforms. Perhaps most importantly, this workflow will allow EOX as a key summary measure in exposome-wide association studies, enabling the identification of novel associations between biomarkers, health outcomes, and halogen exposure. This has the potential to vastly simplify exposure measurement and risk assessment, and provide new insight into the overall exposome burden in human populations.


Title of Project: The Extraordinary Child Hero Organization: A Participant Engagement Project for the Environmental impact on Child Health (ECHO) Study

Principal Investigator: Susan Teitelbaum, PhD

Co-Investigators: Emily Spear

Project Period:  July 27, 2021– July 26, 2022

Pilot Award Amount: $9,713

 

Abstract: Longitudinal cohorts face many barriers to retaining participants. When study benefits are not understood by participants they are more at risk of attrition and this is especially true in pediatric cohorts where many children lack understanding of basic scientific concepts. Additionally, children are often recruited into research studies due to health issues or other adversities they may face, which can make study participation feel stigmatizing. Comic books and graphic novels have been proven to serve as excellent educational tools as well as an effective medium for narrative medicine, the practice of giving voice to the patient, usually through short stories or memoirs. The Environmental impacts on Child Health Outcomes (ECHO) Study is nationwide pediatric cohort seeking to recruit over 50,000 children and their families to assess the influence of environmental factors on childhood health and development. This study is comprised of 72 diverse, on-going maternal-child cohorts, all of which face unique participant retention issues. We propose to create a comic book, which will serve not only as a gift to child participants in the ECHO Study, but will also act as a scientific educational tool explaining environmental health issues central to the ECHO Study, and a form of pediatric narrative medicine by presenting child superheroes with backgrounds recognized amongst ECHO participants. Distribution of this comic book to participants will increase participant engagement and lead to participant retention by emphasizing the distinctive contribution each child can make towards greater scientific knowledge.

PILOT PROJECTS AWARDED 2020 (ROUND 2)

Title of Project: Early-Life Metal Exposure and the Gut Microbiome and Metabolome in Childhood

Principal Investigator (MPI): Shoshannah Eggers, PhD, Manish Arora, BDS, MPH, PhD, FICD

Co-Investigators: Chris Gennings, PhD; Christine Austin, PhD; Jeremiah Faith, PhD; Douglas Walker, PhD; Robert O. Wright, MD, MPH

Project Period: January 18, 2021 – January 17, 2022

Pilot Award Amount: $70,000

 

Abstract: There is increasing recognition of the importance of the human microbiome in health and disease, yet little is known about the effects of environmental toxicant exposures on the development of the microbiome. Early life exposures to metals may program the composition and function of the gut microbiome into childhood, and affect downstream health and development through childhood and the life-course. The purpose of this study is to lay the foundation for a large study on the effects of early life mixed metal exposure on the gut microbiome in childhood, and assess the association between the metal-associated gut microbiome and metabolome. We will leverage the ongoing birth cohort, Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS). Deciduous teeth and blood samples have been collected and analyzed to measure time resolved exposure to multiple metals from the second trimester in utero, through 10yearsold. Stool samples are being collected from participants between 9-11years. Additional demographic data have also been collected. This proposal will fund the analysis of the gut microbiome in stool samples using whole genome shotgun sequencing (n=200), and stool metabolomics in a subset of samples (n=60). Tooth and blood metal exposure data will be linked to the microbiome data to estimate the effects of early-life and childhood metal exposure on the composition and function of the gut microbiome and metabolome in childhood. The proposed project will generate novel evidence in support of future larger grants, and provide valuable insight into the relationship between early-life mixed metal exposures and the gut microbiome in childhood, identifying critical windows of exposure to target in future policies and interventions.


Title of Project: A longitudinal exposomic analysis of breastmilk to determine associations between persistent pollutants, the microbiome and metabolites

Principal Investigator (PI): Ryan Walker, PhD

Co-Investigators: Dania Valvi, PhD; Doug Walker, PhD; Chris Gennings, PhD

Project Period: January 18, 2021 – January 17, 2022

Pilot Award Amount: $25,000

 

Abstract:  Human breastmilk is a complex source of nutrition and is a critical components of growth and development. Exposure, via breastmilk, to persistent organic pollutants (POPs) [specifically perfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDE)] during a critical window of early life developmental programming could have lasting effects on future child health outcomes. Given that early chemical exposure and the development of the infant gut microbiome co-occur during a critical window of infant development, the relationships between POPs, bacteria, and metabolites present in breastmilk merit study. To date no studies have assessed the effect of accumulated PFAS and PBDE exposure in breastmilk on the breastmilk microbiome and its metabolites. We propose to leverage a pre-existing prospective birth cohort study and utilize banked maternal breastmilk samples from a subset of 22 participating mothers. We aim to determine 1] POP levels in prospectively collected breastmilk samples, 2a] if POPs in breast milk are associated with breastmilk microbiome and 2b] if POPs in breastmilk are associated with breastmilk metabolites. We will use untargeted high-resolution mass spectrometry (GC and LC-HRMS) to measure concentrations of known and uncharacterized POPs, annotate breastmilk metabolites and use targeted sequencing of the bacterial DNA to identify changes to breastmilk microbiota across time. To test relationships between chemicals, metabolites and bacteria, we will use weighted quantile sum (WQS) regression with a random subset ensemble step to construct a weighted index of quantile-scored breast milk metabolites or bacteria as related to individual breastmilk PFASs. This pilot proposal will demonstrate feasibility in applying untargeted exposomics to breastmilk, an understudied component of human development. Results from this pilot study will inform a planned R01 proposal with a larger cohort, with repeated breastmilk samples and child outcome measures, to comprehensively study for the first time a breastmilk exposome-microbiome-metabolome link and its association with child health outcomes.


Title of Project: Community-Led Investigation of Air Quality and Environmental Injustice in Proximity to Two Waste Transfer Stations in Jamaica, Queens

Principal Investigator (MPI): Maida P. Galvez, MD, MPH; Luz Guel; Andrea Scarborough; Dawn Roberts Semple, Ph.D; Rebecca Bratspies

Co-I: Danielle Dubno-Hammer

Project Period: January 18, 2021 – January 17, 2022

Pilot Award Amount: $25,000

 

Abstract: When Mayor Giuliani closed the Fresh Kills landfill on Staten Island in the late 1990s, Southeast Queens found itself hosting a growing cluster of private waste transfer stations to process and export garbage to out-of-state landfills. Without a plan to deal with the massive flow of daily trucked trash, the city allowed these heavy industrial facilities to locate in close proximity to homes, parks, and schools in predominantly Black and Brown residential neighborhoods, such as Jamaica, Queens. Residents who live near the two waste transfer stations experience foul odors, diesel exhaust, waste blowoff and leachate, noise, and disruption from these facilities and trucks on a daily basis. In summer, the stench emanating from these waste transfer stations is so unbearable that residents are unable to use their backyards or open their windows. These waste transfer stations are legally obligated to comply with permit restrictions crafted to prevent them from negatively impacting the health and welfare of those living adjacent to the facility. Community science is a novel approach used to address sources of local pollution by in powering community members to lead research that directly affects their community. This pilot project will bring together scientists, community members, and lawyers for an interdisciplinary research collaboration to: 1) build capacity of frontline communities to identify and analyze the frequency and severity of permit violations by providing them with training to lead research, and utilize crowd-sourcing tools to document odor concerns and PM2.5 measurements within a one-mile radius of the stations; 2) inpower residents to use findings to recommend modifications that promote the use of best practices in the facilities’ siting, design, and operation. This project will enable the community to mobilize innovative strategies to ensure proper management of the waste facilities, which will improve their health and quality of life.


Title of Project: Characterizing critical windows of developmental metal mixture effects to kidney development and maturation using transgenic zebrafish

Principal Investigator (MPI): Weibin Zhou, PhD and Alison Sanders, PhD

Co-Investigators: Chris Gennings, PhD; Jaime Chu, PhD

Period:  January 18, 2021 – January 17, 2022

Pilot Award Amount: $25,000

 

Abstract: The zebrafish is a valuable vertebrate model for developmental kidney research. A majority of prior work has focused on the zebrafish pronephros, which comprises only two nephrons and is structurally simpler than the mesonephros of adult fish and the metanephros of humans and other mammals. To evaluate the zebrafish system for more complex studies of kidney development and maturation following toxicant-induced injury, we will investigate the development and post-injury response of the mesonephros in zebrafish Danio rerio. We will examine kidney developmental effects of toxic metals using population-relevant doses. Our population-based preliminary data show that common environmental chemicals such as arsenic (As), lead (Pb), cadmium (Cd), chromium (Cr), and lithium (Li) influence kidney function as early as adolescence, and potentially play a role in early onset of CKD. However, a comprehensive analysis of the effects of chemical toxicant mixtures on kidney development and function throughout the life course remains unknown. Here, we propose to expand prior work to test our hypothesis that developmental nephrotoxicant mixtures, during critical windows of mesonephric kidney development (equivalent to metanephric development in the 2nd and 3rd trimester in humans) program altered histology, gene expression, and functional measures in the developing kidney. We hypothesize that metal mixtures disrupt key genes involved in nephron development as well as glomerular and tubular formation injury and alter glomerular and tubular regeneration following injury. Our team comprises expertise in metals toxicology (mPI Sanders and co-I Chu), zebrafish developmental biology (mPI Zhou and co-I Chu), and chemical mixtures risk assessment and biostatistics (co-I Gennings). Our findings will provide critical preliminary data and demonstrate capacity to succeed as a transdisciplinary team for future mechanistic and translational R01 proposals.


Title of Project: Determining exposure to mixtures of per- and polyfluoroalkyl substances and its association with gestational diabetes in an ethnically diverse U.S. population

Principal Investigator: Damaskini Valvi, MD, MPH, PhD & Syam Andra, PhD

Co-Investigators: Rosalind J Wright, MD, MPH; Elena Colicino, PhD

Project Period:  January 18, 2021 – January 17, 2022

Pilot Award Amount: $25,000

 

Abstract: Per- and polyfluoroalkyl substances (PFASs) are chemicals used in a wide range of consumer products. Previous evidence supports an association of   PFASs exposures with impaired glucose tolerance and gestational diabetes, among other adverse health outcomes. However, underlying mechanisms are not fully understood, and previous studies have focused on few PFASs while the average population is  possibly exposed to hundreds of P  FASs. Moreover, minority racial groups that    may be disproportionally affected by PFASs exposures are underrepresented in the literature. Therefore, we propose to leverage the unique resources of the ethnically diverse U.S. mother-child cohort study ‘Programming of   Intergenerational Stress Mechanisms’ (PRISM) to characterize the PFASs mixture in  serum of pregnant women (Aim 1) and its association with impaired glucose tolerance during gestation (Aim 2a). We will further examine maternal inflammation as a mechanism of   PFASs toxicity in pregnancy (Aim 2   b). For Aim 1, we propose to: (a) use our  proficiency test -validated, low -volume and high  -sensitive targeted liquid chromatography-tandem mass spectrometry (LC -MS) assay for   absolute quantification, and (b) develop a new, cost -efficient, untargeted low -resolution LC-MS assay that    can screen up to 1 00 PFAS suspects, providing the most comprehensive characterization of   PFASs in   human serum up to date. Subsequently in Aim 2, we will evaluate the associations of individual PFASs and the PFASs mixtures with maternal health outcomes (i.e. impaired glucose tolerance and inflammation) using a state  -of-the- art statistical approach for analyzing exposure mixtures that accounts for both additive and multiplicative effects between individual PFASs. Findings will support a  planned R01 submission that aims to leverage the data -rich PRISM mother-child cohort resource to advance the knowledge about the effects of  classical and emerging PFASs and the PFASs mixture in pregnant women by providing a comprehensive characterization of   PFASs exposure and potential mechanisms of toxicity using innovative ‘omics’ biomarkers.

Pilot Projects Awarded 2020 (Round 1)

Title of Project: Leveraging new technologies to assess noise exposure and mobility patterns during COVID-19: a pilot study in NYC women

Principal Investigator (MPI): Laura McGuinn, PhD; Itai Kloog, PhD; Homero Harari, ScD

Co-Investigators: Robert Wright MD, MPH; Rosalind Wright, MD, MPH; Nicholas DeFelice, PhD

Project Period: January 31, 2020 – January 30, 2021

Pilot Award Amount: $25,000

 

Abstract: As the COVID-19 pandemic spread across the globe, several non-pharmaceutical interventions went into place, including social distancing and work from home orders. Though effective, the ability to social distance and work from home is not equal across all geographic regions, socioeconomic gradients, and race/ethnicities. Due to these disparities, the virus causing COVID-19 (SARS-CoV-2) has disproportionately infected lower socioeconomic status (SES) populations and communities of color – populations with historically higher environmental and social stress exposure. Noise exposure is one environmental stressor that has been consistently shown to be higher in lower SES populations. Though many sources of noise have decreased across the country, residential noise exposure has increased dramatically in places such as New York City (NYC). Noise exposure may additionally follow similar socioeconomic gradients during and after the pandemic, and may vary by individual mobility patterns. Wearable devices, such as Apple Watches, are capable of capturing these individual time-varying noise levels, mobility patterns, and activity levels, though their use in population wide studies thus far has been limited. We aim to use pilot funds to take advantage of these novel technologies and 1) compare the performance of the noise meters on wearable devices such as Apple Watches to gold standard noise meters, 2) pilot the use of these devices for the collection of noise and mental health symptoms in a group of racially and socioeconomically diverse women enrolled in the Programming of Intergenerational Stress Mechanisms birth cohort study, and 3) assess if the noise and mental health symptoms differ based on mobility and daily travel patterns. Ultimately, the results from this study will better define mental health impacts of both environmental noise exposure and COVID-related stress, and help provide pilot data for a larger R01 incorporating wearable devices and mental health outcomes.


Title of Project: Untargeted analysis of personal environmental exposures and respiratory outcomes in children

Principal Investigator (MPI): Douglas I. Walker, PhD; Maria José Rosa, DrPH

Co-Investigators: Marcela Tamayo y Ortiz, ScD

Project Period: July 15, 2020 – July 14, 2021

Pilot Award Amount: $25,000

 

Abstract: Indoor and outdoor environmental risk factors for the development and exacerbation of childhood respiratory disease in Latin America remain understudied. Novel personal sampling methods, analytical techniques and big data approaches have been developed that can provide a comprehensive assessment of the external exposome. These new techniques can help researchers understand exposure within the actual microenvironments in which children live and potentially identify novel chemical exposures associated with respiratory disease that in turn may help drive public health interventions. In this proposal we will leverage an ongoing respiratory health study in Mexico City to comprehensively evaluate personal chemical exposures through untargeted analysis of silicone wristband passive samplers. These wristbands are noninvasive and have been validated in multiple populations as tools for environmental monitoring. While most studies have used targeted analysis of chemicals, by using untargeted methods, we can better discover novel exposures that may be driving respiratory outcomes. We will collect these measures in 100 children with lung function measures collected in the study and identify chemical exposures in personal samplers that are associated with lung function measures.


Title of Project: Identifying the role of early environmental toxicants in newborns with biliary atresia
Principal Investigator (MPI): Jaime Chu, MD; Lauren Petrick, PhD

Co-Investigators:  Elena Colicino, PhD; Syam Andra, PhD; Sanjiv Harpavat, MD, PhD

Project Period:  July 15, 2020 – July 14, 2021

Pilot Award Amount: $25,000

 

Abstract:As the COVID-19 pandemic spread across the globe, several non-pharmaceutical interventions went into place, including social distancing and work from home orders. Though effective, the ability to social distance and work from home is not equal across all geographic regions, socioeconomic gradients, and race/ethnicities. Due to these disparities, the virus causing COVID-19 (SARS-CoV-2) has disproportionately infected lower socioeconomic status (SES) populations and communities of color – populations with historically higher environmental and social stress exposure. Noise exposure is one environmental stressor that has been consistently shown to be higher in lower SES populations. Though many sources of noise have decreased across the country, residential noise exposure has increased dramatically in places such as New York City (NYC). Noise exposure may additionally follow similar socioeconomic gradients during and after the pandemic, and may vary by individual mobility patterns. Wearable devices, such as Apple Watches, are capable of capturing these individual time-varying noise levels, mobility patterns, and activity levels, though their use in population wide studies thus far has been limited. We aim to use pilot funds to take advantage of these novel technologies and 1) compare the performance of the noise meters on wearable devices such as Apple Watches to gold standard noise meters, 2) pilot the use of these devices for the collection of noise and mental health symptoms in a group of racially and socioeconomically diverse women enrolled in the Programming of Intergenerational Stress Mechanisms birth cohort study, and 3) assess if the noise and mental health symptoms differ based on mobility and daily travel patterns. Ultimately, the results from this study will better define mental health impacts of both environmental noise exposure and COVID-related stress, and help provide pilot data for a larger R01 incorporating wearable devices and mental health outcomes.


Title of Project: Spatial exploration of inter-relationships of Covid-19 infection, metal exposure, transcriptome and immune response in human placentas

Principal Investigator (MPI): Corina Lesseur, MD, PhD; Megan Niedzwiecki , PhD; Christine Austin, PhD; Kristin G Beaumont, PhD

Co-Investigators: Jia Chen, ScD; Rachel Brody, MD, PhD; Fumiko Dekio, MD

Project Period:  July 15, 2020 – July 14, 2021

Pilot Award Amount: $25,000

 

Abstract: During pregnancy the placenta regulates the intrauterine environment, including maternal immune and hemostatic responses. Little is known about the possible health impacts of the novel respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy or in the placenta. SARS-CoV-2 has been related to inflammatory and thrombotic changes in multiple organs which could also influence placental function. Maternal exposures to trace metals can also influence immunological, hemostatic responses and placental function. We have previously developed a multiplexed approach that integrated spatial metallome (tissue distributions of multiple trace metals) and inflammatory marker immunohistochemistry (IHC) profiling to identify distinct patterns of metal accumulation at sites of inflammation in human placenta. Similarly, recently developed spatial transcriptomic (ST) methods allow for in situ mapping of gene transcripts. In this pilot project, we seek to apply these cutting edge spatial techniques to develop a multimodal imaging pipeline to determine the impact of SARS-CoV-2 infection on the placenta from a systems biology perspective. In term placental tissues (n=6) delivered from SARS-CoV-2 negative mothers (n=2, controls) and from SARS-CoV-2 positive mothers (n=4; 2 without histopathological abnormalities and 2 with histopathological evidence of inflammatory and/or thrombotic lesions) we will profile: 1) protein markers of inflammation and endothelial damage as well as SARS-CoV-2 antigens (IHC), 2) spatial transcriptome-wide mapping and 3) metallome tissue distribution. We will use state-of-the art bioinformatic and statistical approaches to integrate protein markers, gene transcripts and trace metals into a single spatially-resolved map by tissue sample. We hypothesize that SARS-CoV-2 infection induces placental inflammation and vascular injury that co-localize with trace metals element distribution. Our results will provide insight into the biological response to SARS-CoV-2 infection in pregnant women and how metal exposures may alter such response.


Title of Project: Untargeted analysis of personal environmental exposures and respiratory outcomes in children

Principal Investigator: Douglas I. Walker, PhD

Co-Investigators: Robert Wright, MD, MPH; Rosalind J Wright, MD, MPH

Project Period:  July 15, 2020 – July 14, 2021

Pilot Award Amount: $25,000

 

Abstract: The COVID-19 pandemic created a global natural experiment in environmental exposures. Shelter in place orders are nearly universal around the planet, coupled with changes in behavior due to business closures, travel limitations, unemployment, school closures and altered activity levels among other changes, it is clear that our external environment has changed. To estimate these changes, we propose to measure indoor and outdoor environmental factors during and after the pandemic. Novel personal sampling methods, analytical techniques and big data approaches have been developed that can provide a comprehensive assessment of the external exposome. These new techniques can help researchers understand exposure within the actual microenvironments in which children live and potentially identify novel chemical exposures associated with respiratory disease that in turn will help us understand the implications of public health interventions related to the pandemic. In this proposal we will leverage cohort studies in New York City and Mexico City to comprehensively evaluate personal chemical exposures through untargeted analysis of silicone wristband passive samplers. These wristbands are noninvasive and have been validated in multiple populations as tools for environmental monitoring. While most studies have used targeted analysis of chemicals, by using untargeted methods, we can better discover novel exposures that may be driving respiratory outcomes. We will collect these measures in 100 children during and after the pandemic to identify chemical exposures in personal samplers that are associated with public health interventions and societal changes.


Title of Project: Community Engaged Outreach on Environmental Justice.

Principal Investigator (MPI): Luz Claudio, PhD

Co-Investigators: Maya Korin, PhD, MS; Muhammed Y. Idris, PhD

Project Period:  July 15, 2020 – July 14, 2021

Pilot Award Amount: $25,000

 

Abstract: Background: Disadvantaged communities have a disproportionate burden of environmental hazard exposures, increasing health disparities. Health disparities have become even more acute during the COVID-19 pandemic and the subsequent increased awareness of institutional racism that exacerbates these disparities. Now more than ever, there is an urgent need for creative outreach that improves health literacy in minority communities. Objectives: The goal is to adapt and test a mobile platform used by the United Nations Refugee Agency, Compass, to deliver COVID-19 and environmental health information in practical, accessible, health literate manner through trusted community partners. Our aim is to first develop and then test the Enviro-Compass app as a novel way of disseminating health information in underserved communities. This pilot will serve as proof-of-concept for future grant funding. Methods and Expected Outcomes: Compass is a mobile platform and set of developer tools designed to help quickly translate and disseminate practical information to vulnerable communities. We will modify the app in two important ways: 1) incorporate COVID-19 and environmental health information appropriate to the partner community-based organizations, 2) to collect information on usage and effectiveness. Partnering with CBOs that are part of the Arthur Ashe Institute for Urban Health and the New York Environmental Justice Board, we will first recruit two organizations to beta test our app and revise the platform accordingly. Then, we will reach out to community leaders to tailor and disseminate the app to their constituents. A pre-post test will be prompted in the app to measure knowledge gain and retention. Using metrics integrated in the app, we will measure engagement. Data analysis will be done in collaboration with the Center’s Biostatistics Core. We expect that this pilot project will allow us to create and test this app as a novel method for health promotion in hard to reach populations.


Title of Project: A Community-Based Study to Understand the Impacts of COVID-19 on Asthma-related Healthcare Utilization in NYC Children

Principal Investigator (MPI): Nicholas DeFelice, PhD; Erin Thanik, MD, MPH

Co-Investigators: Douglas Bush, MD; Lauren Zajac, MD; Elizabeth Garland MD

Project Period:  July 15, 2020 – July 14, 2021

Pilot Award Amount: $25,000

 

Abstract: The impact of Coronavirus disease 2019 (COVID-19) pandemic across New York City (NYC) is not uniform- the mortality rate in East Harlem (EH) is 4-5 times greater than surrounding neighborhoods. Emerging data suggests that during pandemics other healthcare issues, such as asthma, are overlooked. Nationally, children were 84% less likely to seek care for asthma in emergency departments (EDs) during the initial stages of the pandemic compared to the same period in 2019; little is known about changes to asthma related care for children in EH, who suffer disproportionately from asthma-related morbidity. Objectives: (1) Build on existing community partnership to understand the impact COVID-19 had on the ability of families to seek appropriate asthma care. (2) Evaluate seasonal patterns of environmental exposures associated with asthma-related healthcare in a high-risk pediatric population to develop a forecasting system to inform preventive public health and clinical interventions.

Methods: This community-based participatory research project is in partnership with LSA Family Health Services to collect and analyze survey responses from families in EH with children diagnosed with asthma, compared to families living in a geographically adjacent neighborhood with historically different health outcomes. This survey will evaluate differences in personal behavior, environmental conditions, and health care utilization in response to COVID-19. Additionally, we will develop a statistical inference system to compare historical baseline healthcare utilization patterns for asthma exacerbations attributable to various environmental triggers (air pollutants, pollens, infectious agents) with hospital utilization during the pandemic.

Outcomes and Innovations: Our community survey results will identify barriers to care and concerns regarding environmental exposures, which will inform future public health and clinical responses to optimize care during current and future public health crises. This study will also develop an innovative forecasting system for asthma-related healthcare utilization among NYC children, based on the influence of several environmental variables.

Pilot Projects Awarded 2019 (2)

Title of Project: Environmental Noise and Preadolescent Mental Health in Mexico City

Principal Investigator (MPI): Laura McGuinn, PhD; Itai Kloog, PhD

Co-Investigators: Robert Wright MD, MPH; Homero Harari, ScD; Avi Reichenberg, PhD; Mara Tellez-Rojo, PhD; Ivan Gutierrez, ScD

Project Period: January 31, 2020 – January 30, 2021

Pilot Award Amount: $25,000

 

Abstract: One in four people worldwide will be affected by a mental health disorder at some point in their life, making it a major global contributor to excess morbidity and disability. Depression and anxiety are two of the most common mental health conditions and are a particular issue for younger populations, as the prevalence of both in this age group has continued to increase. Mental health effects from the urban environment are of increasing concern, particularly in mega-cities such as Mexico City. The higher prevalence of mental health conditions in urban areas may be related to social and economic factors, but also factors such as noise pollution that serve as chronic environmental stressors. Noise pollution is of significant concern in Mexico City, as it is estimated to have among the top ten highest noise levels in the world; however, the health effects of noise pollution in this area are not well characterized. Further, while there is a growing body of research on the impact of noise on adult mental health, there is very little research in the younger populations in which chronic depression and anxiety often arises. We will address this novel research question by developing a spatially resolved noise prediction model in Mexico City, then use the resulting estimates to assess the relation between noise and mental health symptoms in preadolescents in the PROGRESS cohort, an ongoing longitudinal birth cohort. Anxiety and depression will be assessed using self-reported measures at age 10-11. The completion of this work will expand knowledge of the health effects of a ubiquitous, yet understudied, exposure and will result in one of the first noise prediction models for Mexico City. The predicted noise estimates developed from this work will be made available to all interested PROGRESS researchers, providing a rich resource for future grant applications.


Title of Project: Untargeted analysis of personal environmental exposures and respiratory outcomes in children

Principal Investigator: Douglas I. Walker, PhD; Maria José Rosa, DrPH

Co-Investigators: Marcela Tamayo y Ortiz, ScD

Project Period:  January 31, 2020 – January 30, 2021

Pilot Award Amount: $20,000

 

Abstract: Indoor and outdoor environmental risk factors for the development and exacerbation of childhood respiratory disease in Latin America remain understudied. Novel personal sampling methods, analytical techniques and big data approaches have been developed that can provide a comprehensive assessment of the external exposome. These new techniques can help researchers understand exposure within the actual microenvironments in which children live and potentially identify novel chemical exposures associated with respiratory disease that in turn may help drive public health interventions. In this proposal we will leverage an ongoing respiratory health study in Mexico City to comprehensively evaluate personal chemical exposures through untargeted analysis of silicone wristband passive samplers. These wristbands are noninvasive and have been validated in multiple populations as tools for environmental monitoring. While most studies have used targeted analysis of chemicals, by using untargeted methods, we can better discover novel exposures that may be driving respiratory outcomes. We will collect these measures in 100 children with lung function measures collected in the study and identify chemical exposures in personal samplers that are associated with lung function measures.


Title of Project: Identifying the role of early environmental toxicants in newborns with biliary atresia
Principal Investigator (MPI): Jaime Chu, MD; Lauren Petrick, PhD

Co-Investigators:  Elena Colicino, PhD; Syam Andra, PhD; Sanjiv Harpavat, MD, PhD

Project Period:   January 31, 2020 – January 30, 2021

Pilot Award Amount: $25,000

 

Abstract: Biliary atresia (BA) is the rapid and progressive destruction of bile ducts in neonates and results in 100% mortality by 1 year if misdiagnosed and left untreated. BA has long been the most common indication for pediatric liver transplantation, yet its etiology remains elusive and the field lacks any biomarkers to aid in early diagnosis. Research focused on GWAS and transcriptomic signatures at 6-8 weeks of age, the typical emergence of visible symptoms, have been unsuccessful at predicting cases of BA. The paradigm is shifting with recent data suggesting 1) a prenatal injury and the need for biomarkers at birth and 2) a role for persistent environmental toxins in BA. Therefore, we propose the first study to investigate toxicant exposure and endogenous biomarker levels in humans, prior to onset of clinical BA symptoms. We will interrogate archived newborn dried blood spots (DBS) collected from neonates that later developed BA and healthy controls. Using innovative methods developed by our team, we will 1) perform targeted quantification of flame retardants, organochlorine pesticides, polyaromatic hydrocarbons, and per- and polyfluoroalkyl substances to determine if infants with biliary atresia have increased prenatal exposure compared to healthy controls and 2) perform untargeted metabolomics analysis to identify differences in metabolite profiles at birth between neonates that later developed biliary atresia compared to healthy neonate controls and ascertain which combination(s) of DBS metabolites increase BA risk as potential pre-diagnosis biomarkers. This proposal addresses the critical unmet need for early and effective biomarkers in BA. We will leverage our diverse and complementary expertise in pediatric liver disease and innovative ability to extract small molecule data from DBS to establish a metabolic signature of infants with BA and introduce the novel prospect that analysis of newborn DBS can offer a window into etiology and earlier diagnosis, and potential transplant-sparing interventions.


Title of Project: Examination of Potential Substances Related to CKD in children (EXPOSURE-CKD Study)

Principal Investigator: Smita Goodman, DO

Co-Investigators: Manish Arora, BDS, MPH, PhD, FICD; Jeffrey Saland, MD; Chris Gennings; PhD

Project Period:  January 31, 2020 – January 30, 2021

Pilot Award Amount: $25,000

 

Abstract: Chronic Kidney Disease (CKD) affects children of all ages and is a major risk for progression to renal failure which is in turn associated with significant morbidity and reduced life expectancy. Environmental exposure studies remain challenging in pediatric populations with CKD. Importantly, tooth-matrix can provide a quantifiable and time-sequenced record of elemental uptake from the second trimester to childhood.  The analytical protocol for the identification of the neonatal zones in enamel and dentine of deciduous teeth and the measurement of metal concentrations in these regions using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) has been validated extensively. In this improved and innovative model of exposure analysis, our reconstruction seeks to yield a biomarker indicative of a potential early life determinant of CKD in children. We hypothesize there is a prenatal and early life exposure to essential and toxic elements during critical development windows that is associated with pediatric CKD. We propose an IRB-approved case-control pilot study using validated tooth-matrix biomarkers to obtain time-sequenced quantifiable elemental exposure profiles in children with a diagnosis of CKD. We are recruiting subjects from the clinical practice of the Division of Pediatric Nephrology and patients meet criteria as a case if they are a patient 0-21 years old with a diagnosis of CKD and shed tooth for collection. The focus of our study population is patients with renal anomalies (e.g. structural anomaly of the genitourinary tract, nephrotic syndrome with urine protein loss) that have renal damage but maintain normal or mild decline in renal filtration function. This is not a study population focused on patients with end stage renal disease.  Controls are age and gender matched healthy subjects without CKD enrolled from an ongoing study at the Seaver Center at Mount Sinai.  Exposure metrics focus on known metal nephrotoxins (arsenic, cadmium, lead, mercury) with an additional exploratory analysis of zinc, copper, manganese, and magnesium. Outcome metrics are an established diagnosis of pediatric CKD.  As tooth development begins in the second trimester, all shed teeth have a record of exposure that predates the diagnosis of CKD. Our two aims are as follows: (1): Identify quantifiable differences in environmental exposure profiles of individual essential and toxic elements present in the tooth record of the pediatric CKD population as compared to controls without CKD (that is, associations of single elements with CKD).  (2) Identify the joint association of exposure of essential and toxic elements as a mixture occurring in the pediatric CKD population. As this type of detailed multiple-analyte tooth investigation has never been performed in this population, this proposed study will allow us to make preliminary determinations about time-sequenced patterns of element exposure expressed in the tooth record of children with renal disease that will enable future research in this population. Our goal is to use novel biomarkers of early life exposure to increase understanding of potential modifiable environmental exposures in the childhood CKD population and lay the foundation for larger studies that explore the early life determinants of CKD. The results of this pilot project will serve as the foundation of the applicant’s K grant application.


Title of Project: The Relationship between Neonatal Intensive Care Unit (NICU) Stress, Telomere Length, and Neurodevelopment in Preterm Infant

Principal Investigator (MPI): Xueying Zhang, PhD; Annemarie Stroustrup, MD, MPH

Co-Investigators: Andrea Baccarelli, PhD

Project Period:  January 31, 2020 – January 30, 2021

Pilot Award Amount: $20,000

 

Abstract: Moderately preterm infants are at elevated risk of adverse neurobehavioral outcomes. Emerging data has linked exposure to environmental stress and chemicals in the neonatal intensive care unit (NICU) to alterations in neurodevelopment. Recent studies indicate that telomere length may be a useful indicator of environmental exposures, and also associated with neurologic outcomes in non-NICU populations. Leukocyte telomere length change has been shown to be meaningful during the NICU hospitalization. The proposed research will investigate the association between established biomarkers of NICU stress response and chemical exposure with the change rate of telomere length for hospitalized preterm infants enrolled in the NICU Hospital Exposures and Long-Term Health (NICU-HEALTH) cohort. Additionally, we will investigate the association between the change rate of telomere length and early neurobehavioral performance. Findings of this study will provide critical preliminary data for a definitive study of the role of telomere length on the pathway between NICU-based environmental exposures and preterm infant neurobehavioral disorders.


Title of Project: Exposure to Perfluoroalkyl Substances, Metabolomic Profiling, and Type 2 Diabetes Risk: A Prospective Investigation in an Ethnically Diverse U.S. Population.

Principal Investigator (MPI): Damaskini Valvi, MD, MPH, PhD

Co-Investigators:  Ruth Loos, PhD; Douglas Walker, PhD

Project Period:  January 31, 2020 – January 30, 2021

Pilot Award Amount: $70,000

 

Abstract: The prevalence of type 2 diabetes (T2D) has almost tripled over the past 40 years in the U.S., currently affecting more than 20 million people. Mounting evidence from studies in vivo and in vitro shows that exposures to environmental chemicals, such as perfluoroalkyl substances (PFAS), can alter insulin secretion and promote impaired glucose tolerance, and may therefore contribute to the T2D epidemic. PFAS constitute a major public health issue, as current exposure is widespread in the general population through contaminated drinking water and food along other possible exposure sources, and potentially associated health risks are not fully understood. Despite abundant experimental data, population-based evidence on the association of PFAS with T2D risk is limited, almost exclusively comprised by cross-sectional studies, and underlying mechanisms are underexplored. Therefore, we propose to investigate the prospective associations of PFAS exposures with incidence of T2D, and potential underlying mechanisms using state-of-the-art untargeted high-resolution metabolomics (HRM) technologies. We will conduct a prospective nested case-control study by selecting 180 incident T2D cases and 180 controls matched by age, sex, ancestry and calendar year at blood draw, from Mount Sinai’s BioMe. BioMe is an ongoing electronic health record-linked biobank that comprises >50,000 adult participants enrolled since 2007, with a broad spectrum of longitudinal data on health outcomes and clinical markers already recorded, and genome-wide array data available. We will utilize the unique archive of plasma samples collected from all BioMe participants at study entry (i.e. prior to T2D diagnosis), representing an ethnically diverse population residing in New York, to characterize exposure to PFAS and untargeted metabolomic pathways. Findings will support a planned R01 application to conduct the largest prospective study of well-phenotyped incident T2D cases to date, on the associations of PFAS exposures with the metabolome and T2D risk, as well as gene-environment interactions.


Title of Project: Phthalates and the developing brain: a multidisciplinary investigation of the effects of prenatal phthalate exposure on early markers of ADHD

Principal Investigator (MPI): Anna Rommel, PhD; Avi Reichenberg, PhD

Co-Investigators:  Shanna Swan, PhD; Muhammad Parvaz, PhD

Project Period:  January 31, 2020 – January 30, 2021

Pilot Award Amount: $20,000

 

Abstract: Phthalate plasticizers are ubiquitous in consumer products and can be detected in almost all pregnant women. Phthalates cross the placental and blood–brain barriers, affecting fetal brain development and subsequent functioning. Prenatal exposure to phthalates has been associated with adverse cognition and behaviour in areas central to attention deficit hyperactivity disorder (ADHD), including inattention and externalizing behaviours, and with increased risk for ADHD diagnosis. ADHD is the most prevalent neurodevelopmental disorder with enormous personal, medical and societal costs. Thus, early detection and intervention are crucial. Research has documented robust behavioural, cognitive and neurophysiological differences between individuals with ADHD and typically developing controls, which emerge in infancy and predict ADHD symptomatology later in life. These include activity levels, negative temperament, inattention, and alterations in event-related potentials (ERPs) indexing attention (i.e. P2 and P3). ERPs are electrical potentials generated by the brain in response to stimuli, which permit direct examinations of brain processes with millisecond temporal resolution. Here, we seek to obtain feasibility data to understand the biological basis via which phthalates alter brain and behavioral functioning to increase risk for ADHD. To do so, we propose to investigate the effects of 11 phthalates (MCPP, MEP, MIBP, MBP, MECPP, MEHHP, MEOHP, MBZP, MEHP, MCiOP, MCiNP) on neurophysiological development using ERPs indexing attention (P2 and P3) elicited by an auditory oddball task, and on behavioural and cognitive development using the Infant Behavior Questionnaire and the Ages and Stages Questionnaire. The significance of this study lies in the ability to provide a novel, objective method for assessing neural processes underlying the impact of intrauterine phthalate exposure on neurodevelopment and the earliest markers of ADHD. Identifying risk early is crucial for timely interventions to minimize the potential adverse effects of intrauterine phthalate exposure.

 

Pilot Projects Awarded 2019

Title of Project: Defining Integrated Environmental Exposure Measures in Adolescents

Principal Investigator (MPI): Yuri Levin-Schwartz, PhD; Robert Wright, MD, MPH

Co-Investigators: Elena Colicino, PhD; Donald R. Smith PhD

Project Period: July 1, 2019 – June 30, 2020

Pilot Award Amount: $25,000

 

Abstract: The measurement of a compound in a single biological sample is unlikely to fully represent the relative body burden of an environmental exposure, since no single tissue can encapsulate the overall toxicokinetics for most chemicals. Yet, this is the most commonly used surrogate of chemical exposure in environmental epidemiology research. Since each exposure biomarker provides complementary information about the level of exposure, we propose to develop and use methods that will take advantage of this information to create integrated exposure estimates, referred to as multi-media biomarkers (MMBs). As part of the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort, our group has collected samples of multiple biological media (blood, nails, urine, hair, bone and shed deciduous teeth) from mothers during pregnancy and after pregnancy. In this proposal, we will measure the concentrations of lead (Pb) in 100 women using stored urine from the second trimester of pregnancy and first month postpartum as well as nails from the same women from the first month postpartum to match similar measurements already done using the other media. Using exposure estimates from each medium, we will compare the utility of the individual media with that of the MMBs to assess to impact of Pb exposure, measured prenatally and postnatally, on neurodevelopment in the children as well as determine the existence of any window of susceptibility. This proposed work has the potential to transform environmental exposure quantification from the selection of one media over others to the joint use of multiple media to derive more accurate measures of exposure.


Title of Project: Environmental control of mitochondrial division as a signal to initiate skin cancer

Principal Investigator:  Jerry Chipuk, PhD

Project Period:   July 1, 2019 – June 30, 2020

Pilot Award Amount: $25,000

 

Abstract:  The skin is a fascinating and complex organ because it protects the body from the environment, microbes, and coordinates a multitude of homeostatic functions. Within the skin are neural crest derived melaninproducing cells known as melanocytes which offer protection from the sun’s damaging UV radiation. Melanocytes often develop an activating mutation in RAS (G12V) or BRAF (V600E) causing unwarranted proliferation that activates a tumor suppressor program referred to as oncogene-induced senescence (OIS). OIS initiates epigenetic, metabolic, and secretory reprogramming that arrests the targeted cell in a senescent state. Clusters of senescent melanocytes are clinically referred to as a nevus (i.e., mole), and they persist for decades. Over the decades, it is suggested that additional alterations from endogenous or environmental factors impact upon a few of these cells within a nevus to promote their escape from senescence leading to malignant transformation and melanomagenesis. In this application, we propose to establish that environmental factors such as heavy metals and ultraviolet radiation directly signal for mitochondrial division to promote OIS escape leading to melanoma. The premise for this application is our unpublished dataset using primary human melanocytes that we commit to RASG12V- or BRAFV600E-induced senescence and culture for months. These senescent melanocytes express all the normal markers and cytokines as patient nevi. When we induce senescence with lentivirus encoding for oncogenic RAS/BRAF, we also silently introduce a pharmacologically activated mitochondrial dynamin (dynamin related protein 1, DRP1) that can physiologically divide the mitochondrial network within a few minutes. Turning on DRP1 after a few months of senescence causes a subset of senescent melanocytes to escape from OIS and transform. Based on the literature, heavy metals and ultraviolet radiation alone cause mitochondrial stress and division, but no mechanistic links have been established to OIS or cancer. We wish to fill this knowledge gap with this pilot award and generate sufficient preliminary data for an R01 application.


Title of Project: Exposomics for agricultural workers in Costa Rica affected by chronic kidney disease of unknown etiology (CKDu)
Principal Investigator (MPI): Alison Sanders, PhD; Douglas Walker, PhD

Co-Investigators:  Jennifer Crowe, MPH, PhD; Andres Cardenas, PhD, MPH; Chris Gennings, PhD

Project Period:   July 1, 2019 – June 30, 2020

Pilot Award Amount: $69,608

 

Abstract: Chronic Kidney Disease of unknown etiology (CKDu) is a public health emergency in Central America and regions of Sri Lanka and India. CKDu affects agricultural workers and communities and it is not explained by traditional risk factors for kidney disease like age, hypertension or diabetes. Underlying factors contributing to the epidemic are unknown but likely multifactorial. Occupational exposure to agrochemicals, heat stress and metals are among the leading hypotheses; however, studies have focused on only a limited number of environmental exposures that are not representative of the complex exposures likely experienced by agricultural workers. Use and reuse of agricultural land and agrochemicals might transform, volatilize and degrade compounds, which would be missed by targeted chemical screenings. In this study, we will develop a framework to comprehensively characterize the exposome and complex mixture profiles of agricultural workers in a province of Costa Rica heavily affected by the CKDu epidemic. To achieve this goal, we will leverage an ongoing study of farmworkers in the region with well-characterized job history and baseline kidney function measures. We will deploy silicone wristbands as passive samplers for untargeted chemical screening during the workweek and will collect pre- and post-work urine samples to evaluate wristband profiles as a proxy for urinary exposure biomarkers. Our team includes experts in occupational health (co-I: Crowe), environmental/molecular epidemiology (co-I: Cardenas and co-PI: Sanders), exposomics and metabolomics (co-PI: Walker), biostatistics (co-I: Gennings) and renal epidemiology/toxicology (co-PI: Sanders). This work will advance our understanding of environmental exposures among CKDu affected farmworkers allowing us to compare and contrast exposure profiles within different job types. The proposed research will provide ample pilot data and samples for future R01 applications evaluating the exposome of populations at risk of CKDu for informing future interventions designed to prevent nephrotoxic occupational co-exposures.


Title of Project: Using deciduous teeth to assess children’s exposure to tobacco, marijuana, and other environmental toxins

Principal Investigator: Karen Wilson, MD, MPH

Co-Investigators: Manish Arora, BDS, MPH, PhD, FICD; Syam Andra, PhD

Project Period:  July 1, 2019 – June 30, 2020

Pilot Award Amount: $70,000

 

Abstract: With increasing marijuana legalization across the US, there are more opportunities for children to be exposed to secondhand marijuana smoke; however, we don’t have any research to explore the impact of marijuana smoke exposure on children’s health. We do not understand the prevalence of exposure among children, or whether there is coexposure with tobacco, or with pesticides used in the production of marijuana. Current research methods, especially in looking at long term exposure and outcomes, are significantly limited by ongoing fears of reporting children with exposure to children’s services. Analysis of shed deciduous teeth offers the opportunity to collect teeth and data anonymously, and yet still have a longitudinal picture of a child’s exposure, both prenatally and postnatally. Our project seeks to demonstrate this strategy and test the technology by recruiting 100 children from the Pediatric Associates Clinic, and obtain an anonymous parent report of exposures, health history, and current health. Parents will then return the child’s shed deciduous tooth to the study team, whether it will be analyzed in the lab for metabolites of marijuana and tobacco, electronic cigarette aerosol, and pesticides. This preliminary data will be critical for submission of an R01 to study the impact of marijuana smoke exposure on the health of children.


Title of Project: Innovating Data Visualization Strategies for Tooth-Based Lead Report-Back

Principal Investigator (MPI): Sarah Evans, PhD, MPH; Manish Arora, BDS, MPH, PhD, FICD; Maida Galvez, MD, MPH

Co-Investigators: Alison Mears, AIA

Project Period:  July 1, 2019 – June 30, 2020

Pilot Award Amount: $20,000

 

Abstract: Reporting back biomonitoring data to study subjects has the potential to improve health literacy and promote exposure reduction behaviors. Technological advances in the field of exposure assessment allow for detection of biomarkers in novel matrices and measurement of multiple exposures across time, but resultant data is complex and clinical relevance is often uncertain. This poses unique challenges for communication of individual exposure data to study subjects in an understandable and meaningful way. Using methods pioneered in the Frank R. Lautenberg Laboratory for Environmental Health Sciences at Mount Sinai, we are able to reconstruct early life exposures to lead and other chemicals using deciduous teeth, contributing to our understanding of critical developmental periods during which organ systems are most susceptible to harm. This proposal seeks to develop effective strategies for reporting back individual child tooth lead data to families enrolled in birth cohort studies with the aim of promoting exposure-reduction behaviors. Given clinical uncertainty and the lack of normative data on tooth-lead levels, communicating results requires an innovative approach. To address these challenges, we will partner with students from the Parsons School of Design to create a novel, multi-modal strategy for reporting tooth lead levels to study subjects. This team science approach allows for cross-talk between environmental health scientists and data visualization and communication experts to create impactful public health messaging. Reports will include individual and aggregate tooth lead data, information about the health effects of lead exposure, and exposure reduction tips. Usability and efficacy of the developed materials will be tested in focus groups with English and Spanish speaking members of the East Harlem community. Feedback received will be used to modify the report-back strategy for future studies in which tooth lead data will be disseminated to participants in active birth cohort studies in the United States and Mexico.


Title of Project: Predicting response to immunotherapy in hepatocellular carcinoma by dissecting the gut microbiome: a pilot study

Principal Investigator (MPI): Amaia Lujambio, PhD; Celina Ang, MD; Jeremiah Faith, PhD

Co-Investigators:  Andrea Branch, PhD; Lauren Grinspan, MD; Tomi Jun, MD

Project Period:  July 1, 2019 – June 30, 2020

Pilot Award Amount: $50,000

 

Abstract: Background: Hepatocellular carcinoma (HCC) is a common and deadly cancer of the liver. Newlyapproved immune checkpoint inhibitors (ICIs) such as nivolumab can produce durable responses, but only 15-20% of patients respond to these treatments. Studies have suggested that the gut microbiome – – the microbial community of the digestive tract that forms a stable immunomodulatory component of our environment — may influence patients’ responses to immunotherapy. We propose a pilot study to determine whether the gut microbiome influences patients’ response to ICIs in HCC. Objectives: In this proposal, we study the fecal microbiome of 50 HCC patients before and after receiving an ICI (nivolumab or pembrolizumab) to test the following hypotheses: 1) Microbial taxa and diversity differ between ICI responders and non-responders in advanced HCC. 2) Changes in the gut microbiota that occur following ICI treatment differ between ICI responders and non-responders. 3) Gnotobiotic mice receiving fecal transplants from responders will exhibit greater response to ICIs compared to mice receiving fecal transplants from non-responders. Methods: We will collect pre- and 8 week-post-treatment stool and blood samples from patients with advanced HCC who receive an ICI. Stool microbial composition will be determined using 16S rRNA sequencing. Mouse studies will make use of a novel CRISPR-Cas9 based model of HCC carcinogenesis optimized to study immunotherapies. Significance/innovation: This proposal takes advantage of the large HCC patient population at Mount Sinai and the combined effort of investigators across the institution with expertise in oncology, in vivo liver cancer models, and the gut microbiome, to understand the role of the gut microbiome as an environmental factor that modulates the efficacy of ICIs in HCC. This pilot award will enable us to generate preliminary data necessary to be competitive for a recently announced RFA from the NIH that is devoted to microbiota-manipulation strategies for cancer therapy.

 


Title of Project: Using eye-tracking to Identify associations between metal exposure and children’s social cognition: A pilot study in Mexico City

Principal Investigator (MPI): Elza Rechtman, PhD; Megan Horton, PhD

Co-Investigators:  Roberto Lucchini, MD; Paul Curtin, PhD; Manish Arora, BDS, MPH, PhD, FICD; Christine Austin, PhD

Project Period:  July 1, 2019 – June 30, 2020

Pilot Award Amount: $25,000

 

Abstract: Social cognition refers to the cognitive process by which humans infer the state of mind of others and anticipate their reactions. This complex skill relies on integrated information processing, including the perception of social cues gathered from faces, eyes, hands and body of others. Growing research indicates that early life exposure to neurotoxicant metals including lead and manganese is associated with maladaptive social behavior. Although promising, these findings have been based on self- and parent-reports of social behavior which suffer from response biases. While the value of collecting objective phenotyping measures along with surveys has long been recognized, the majority of large-scale community and population studies rely on survey reports of social behavior. In this costeffective and innovative proposal, we propose to use eye-tracking as an objective phenotyping tool for detecting environmentally-associated changes in social cognition. Eye-tracking is a simple, rapid, non-invasive, sensitive and quantitative method enabling of recording spontaneous, unconscious gaze behavior towards socially relevant cues that provides insight into neural processing. We hypothesize that early life metal exposure adversely impacts social perception and that eye-tracking is a more sensitive assessment of environmentally-induced changes in neural connectivity. To test this, we leverage the PROGRESS study with existing longitudinal exposure and behavioral measurements and ongoing follow-up including high-resolution neuroimaging. We propose to add a recognized naturalistic eye-tracking paradigm of clips displaying peer-to-peer social interactions, and measure viewing time and number of fixations at the eyes, mouth, and faces of characters. We will examine associations between early life Pb and Mn exposure (in blood and teeth) and social cognition using eye tracking and parent-reported scale of social behavior. We will then investigate associations between early life metal exposure and intrinsic functional connectivity of the social brain. To our knowledge, no other study has attempted to investigate associations between similar aspects of social cognition, longitudinal assessment of early life metal exposure and high-resolution brain imaging.

 


Title of Project: Secondhand smoke in Central and East Harlem: Understating cancer survivors’ and family caregivers’ perceptions of the health consequences of involuntary and voluntary exposure to tobacco smoke

Principal Investigator (MPI): Nihal E. Mohamed, PhD; Lina Jandorf, MA

Co-Investigators:  Karen Wilson, MD, MPH

Project Period:  July 1, 2019 – June 30, 2020

Pilot Award Amount: $50,000

 

Abstract: Prior research showed that approximately half (46.8%) of African Americans (AA) and a quarter (23.9%) of Hispanic nonsmokers are exposed to secondhand smoke (SHS) in the US. This exposure is high in individuals with low socioeconomic levels, and in particular among those living in multiunit and subsidized housing conditions. The impact of SHS might be more detrimental for AA and Hispanic cancer survivors who live in multiunit and subsidized housing. Reported challenges in physician-patient communication about smoking cessation also indicate that a discussion about SHS exposure and risk might be insufficient because of the fear of damaging therapeutic relationships, concerns about exacerbating patients’ guilt, and lack of physician’s good understanding about SHS risks and prevention. Unfortunately, studies on SHS in at-risk AA and Hispanic cancer survivors and their family caregivers are limited. Guided by an established theoretical framework, literature reviews, and our prior studies, we will (Aim 1-a/b) explore cancer survivors’ and caregivers’ perceptions about their exposure, (i.e., both voluntary and involuntary) and how it affects their health; and (Aim 1-c) how SHS exposure affects the health of children living in their communities. We will recruit 30 survivors living in public housing in East and Central Harlem and their family caregivers (N = 30) to examine the study aims. Participants will be invited to participate in 12 focus groups. Focus groups will be stratified by race, role (survivors/caregiver) and smoking status (nonsmoker vs. smoker) to examine: 1) knowledge, impact on health, and salient beliefs about exposure to SHS; and 2) input on successful strategies to prevent SHS. All focus groups will be qualitatively analyzed using Atlas.ti software. The study outcomes will inform the design of a biobehavioral study to assess actual exposure (Cotinine levels), risk perceptions, health beliefs, and health outcomes in AA and Hispanic cancer survivors and their caregivers.

 

Pilot Projects Awarded 2019

Title of Project: Using deciduous teeth to assess children’s exposure to tobacco, marijuana, and other environmental toxins
Principal Investigator: Karen M. Wilson, MD, MPH

Co-Investigators: Manish Arora, BDS, MPH, PhD, FICD; Syam Andra, PhD

Project Period:  July 1, 2019 – June 30, 2020

Pilot Award Amount: $70,000

 

Abstract: 

With increasing marijuana legalization across the US, there are more opportunities for children to be exposed to secondhand marijuana smoke; however we don’t have any research to explore the impact of marijuana smoke exposure on children’s health. We do not understand the prevalence of exposure among children, or whether there is coexposure with tobacco, or with pesticides used in the production of marijuana. Current research methods, especially in looking at long term exposure and outcomes, are significantly limited by ongoing fears of reporting children with exposure to children’s services. Analysis of shed deciduous teeth offers the opportunity to collect teeth and data anonymously, and yet still have a longitudinal picture of a child’s exposure, both prenatally and postnatally. Our project seeks to demonstrate this strategy and test the technology by recruiting 100 children from the Pediatric Associates Clinic, and obtain an anonymous parent report of exposures, health history, and current health. Parents will then return the child’s shed deciduous tooth to the study team, whether it will be analyzed in the lab for metabolites of marijuana and tobacco, electronic cigarette aerosol, and pesticides. This preliminary data will be critical for submission of an R01 to study the impact of marijuana smoke exposure on the health of children.


Title of Project: Exposomics for agricultural workers in Costa Rica affected by chronic kidney disease of unknown etiology (CKDu)
Principal Investigator: Alison Sanders, PhD; Douglas Walker, PhD

Co-Investigators: Chris Gennings, PhD; Jennifer Crowe, Professor II, IRET, Universidad Nacional, Heredia, Costa Rica; Andres Cardenas, Assistant Professor, University of California, Berkeley, School of Public Health

Project Period: July 1, 2019 – June 30, 2020

Pilot Award Amount: $69,608

 

Abstract:

Chronic Kidney Disease of unknown etiology (CKDu) is a public health emergency in Central America and regions of Sri Lanka and India. CKDu affects agricultural workers and communities and it is not explained by traditional risk factors for kidney disease like age, hypertension or diabetes. Underlying factors contributing to the epidemic are unknown but likely multifactorial. Occupational exposure to agrochemicals, heat stress and metals are among the leading hypotheses; however, studies have focused on only a limited number of environmental exposures that are not representative of the complex exposures likely experienced by agricultural workers. Use and reuse of agricultural land and agrochemicals might transform, volatilize and degrade compounds, which would be missed by targeted chemical screenings. In this study, we will develop a framework to comprehensively characterize the exposome and complex mixture profiles of agricultural workers in a province of Costa Rica heavily affected by the CKDu epidemic. To achieve this goal, we will leverage an ongoing study of farmworkers in the region with well-characterized job history and baseline kidney function measures. We will deploy silicone wristbands as passive samplers for untargeted chemical screening during the workweek and will collect pre- and post-work urine samples to evaluate wristband profiles as a proxy for urinary exposure biomarkers. Our team includes experts in occupational health (co-I: Crowe), environmental/molecular epidemiology (co-I: Cardenas and co-PI: Sanders), exposomics and metabolomics (co-PI: Walker), biostatistics (co-I: Gennings) and renal epidemiology/toxicology (co-PI: Sanders). This work will advance our understanding of environmental exposures among CKDu affected farmworkers allowing us to compare and contrast exposure profiles within different job types. The proposed research will provide ample pilot data and samples for future R01 applications evaluating the exposome of populations at risk of CKDu for informing future interventions designed to prevent nephrotoxic occupational co-exposures.


Title of Project: Secondhand smoke in Central and East Harlem: Understating cancer survivors’ and family caregivers’ perceptions of the health consequences of involuntary and voluntary exposure to tobacco smoke

Principal Investigator: Nihal E. Mohamed, PhD; Lina Jandorf, MA

Co-Investigators: Karen Wilson, MD, MPH

Project Period: July 1, 2019 – June 30, 2020

Pilot Award Amount: $50,000

 

Abstract: 

Prior research showed that approximately half (46.8%) of African Americans (AA) and a quarter (23.9%) of Hispanic nonsmokers are exposed to secondhand smoke (SHS) in the US. This exposure is high in individuals with low socioeconomic levels, and in particular among those living in multiunit and subsidized housing conditions. The impact of SHS might be more detrimental for AA and Hispanic cancer survivors who live in multiunit and subsidized housing. Reported challenges in physician-patient communication about smoking cessation also indicate that a discussion about SHS exposure and risk might be insufficient because of the fear of damaging therapeutic relationships, concerns about exacerbating patients’ guilt, and lack of physician’s good understanding about SHS risks and prevention. Unfortunately, studies on SHS in at-risk AA and Hispanic cancer survivors and their family caregivers are limited. Guided by an established theoretical framework, literature reviews, and our prior studies, we will (Aim 1-a/b) explore cancer survivors’ and caregivers’ perceptions about their exposure, (i.e., both voluntary and involuntary) and how it affects their health; and (Aim 1-c) how SHS exposure affects the health of children living in their communities. We will recruit 30 survivors living in public housing in East and Central Harlem and their family caregivers (N = 30) to examine the study aims. Participants will be invited to participate in 12 focus groups. Focus groups will be stratified by race, role (survivors/caregiver) and smoking status (nonsmoker vs. smoker) to examine: 1) knowledge, impact on health, and salient beliefs about exposure to SHS; and 2) input on successful strategies to prevent SHS. All focus groups will be qualitatively analyzed using Atlas.ti software. The study outcomes will inform the design of a biobehavioral study to assess actual exposure (Cotinine levels), risk perceptions, health beliefs, and health outcomes in AA and Hispanic cancer survivors and their caregivers.


Title of Project: Predicting response to immunotherapy in hepatocellular carcinoma by dissecting the gut microbiome: a pilot study

Principal Investigator: Amaia Lujambio, PhD (TCI); Celina Ang, MD (TCI); Feremiah Faith, PhD (TCI)

Co-Investigators: Andrea Branch, PhD (TCI); Lauren Grinspan, Gastroenterology Fellow; Tomi Jun, MD, Hematology-Oncology Fellow.

Project Period: July 1, 2019 – June 30, 2020

Pilot Award Amount: $50,000

 

Abstract:

Background: Hepatocellular carcinoma (HCC) is a common and deadly cancer of the liver. Newly approved immune checkpoint inhibitors (ICIs) such as nivolumab can produce durable responses, but only 15-20% of patients respond to these treatments. Studies have suggested that the gut microbiome — the microbial community of the digestive tract that forms a stable immunomodulatory component of our environment — may influence patients’ responses to immunotherapy. We propose a pilot study to determine whether the gut microbiome influences patients’ response to ICIs in HCC.

 

Objectives: In this proposal, we study the fecal microbiome of 50 HCC patients before and after receiving an ICI (nivolumab or pembrolizumab) to test the following hypotheses: 1) Microbial taxa and diversity differ between ICI responders and non-responders in advanced HCC. 2) Changes in the gut microbiota that occur following ICI treatment differ between ICI responders and non-responders. 3) Gnotobiotic mice receiving fecal transplants from responders will exhibit greater response to ICIs compared to mice receiving fecal transplants from non responders.

 

Methods: We will collect pre- and 8 week-post-treatment stool and blood samples from patients with advanced HCC who receive an ICI. Stool microbial composition will be determined using 16S rRNA sequencing. Mouse studies will make use of a novel CRISPR-Cas9 based model of HCC carcinogenesis optimized to study immunotherapies.

 

Significance/innovation: This proposal takes advantage of the large HCC patient population at Mount Sinai and the combined effort of investigators across the institution with expertise in oncology, in vivo liver cancer models, and the gut microbiome, to understand the role of the gut microbiome as an environmental factor that modulates the efficacy of ICIs in HCC. This pilot award will enable us to generate preliminary data necessary to be competitive for a recently announced RFA from the NIH that is devoted to microbiota-manipulation strategies for cancer therapy.


Title of Project: Defining Integrated Environmental Exposure Measures in Adolescents

Principal Investigator: Yuri Levin-Schwartz, PhD; Robert Wright, MD, MPH

Co-Investigators:  Elena Colicino, PhD; Donald R. Smith, PhD

Project Period: July 1, 2019 – June 30, 2020

Pilot Award Amount: $25,000

 

Abstract: 

The measurement of a compound in a single biological sample is unlikely to fully represent the relative body burden of an environmental exposure, since no single tissue can encapsulate the overall toxicokinetics for most chemicals. Yet, this is the most commonly used surrogate of chemical exposure in environmental epidemiology research. Since each exposure biomarker provides complementary information about the level of exposure, we propose to develop and use methods that will take advantage of this information to create integrated exposure estimates, referred to as multi-media biomarkers (MMBs). As part of the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort, our group has collected samples of multiple biological media (blood, nails, urine, hair, bone and shed deciduous teeth) from mothers during pregnancy and after pregnancy. In this proposal, we will measure the concentrations of lead (Pb) in 100 women using stored urine from the second trimester of pregnancy and first month postpartum as well as nails from the same women from the first month postpartum to match similar measurements already done using the other media. Using exposure estimates from each medium, we will compare the utility of the individual media with that of the MMBs to assess to impact of Pb exposure, measured prenatally and postnatally, on neurodevelopment in the children as well as determine the existence of any window of susceptibility. This proposed work has the potential to transform environmental exposure quantification from the selection of one media over others to the joint use of multiple media to derive more accurate measures of exposure.


Title of Project: Environmental control of mitochondrial division as a signal to initiate skin cancer

Principal Investigator: Jerry Edward Chipuk, PhD

Co-Investigators: N/A

Project Period:  July 1, 2019 – June 30, 2020

Pilot Award Amount: $25,000

 

Abstract:

The skin is a fascinating and complex organ because it protects the body from the environment, microbes, and coordinates a multitude of homeostatic functions. Within the skin are neural crest derived melaninproducing cells known as melanocytes which offer protection from the sun’s damaging UV radiation. Melanocytes often develop an activating mutation in RAS (G12V) or BRAF (V600E) causing unwarranted proliferation that activates a tumor suppressor program referred to as oncogene-induced senescence (OIS). OIS initiates epigenetic, metabolic, and secretory reprogramming that arrests the targeted cell in a senescent state. Clusters of senescent melanocytes are clinically referred to as a nevus (i.e., mole), and they persist for decades. Over the decades, it is suggested that additional alterations from endogenous or environmental factors impact upon a few of these cells within a nevus to promote their escape from senescence leading to malignant transformation and melanomagenesis. In this application, we propose to establish that environmental factors such as heavy metals and ultraviolet radiation directly signal for mitochondrial division to promote OIS escape leading to melanoma. The premise for this application is our unpublished dataset using primary human melanocytes that we commit to RASG12V- or BRAFV600E-induced senescence and culture for months. These senescent melanocytes express all the normal markers and cytokines as patient nevi. When we induce senescence with lentivirus encoding for oncogenic RAS/BRAF,
we also silently introduce a pharmacologically activated mitochondrial dynamin (dynamin related protein 1, DRP1) that can physiologically divide the mitochondrial network within a few minutes. Turning on DRP1 after a few months of senescence causes a subset of senescent melanocytes to escape from OIS and transform. Based on the literature, heavy metals and ultraviolet radiation alone cause mitochondrial stress and division, but no mechanistic links have been established to OIS or cancer. We wish to fill this knowledge gap with this pilot award and generate sufficient preliminary data for an R01 application.


Title of Project: Using eye-tracking to Identify associations between metal exposure and children’s social cognition: A pilot study in Mexico City

Principal Investigator: Megan Horton, PhD, MPH; Elza Rechtman, PhD

Co-Investigators: Paul Curtin, PhD; Robert Wright, MD, MPH; Manish Arora, BDS, MPH, PhD, FICD; Mara Tellez Rojo

Project Period: July 1, 2019 – June 30, 2020

Pilot Award Amount: $25,000

 

Abstract: 

Social cognition refers to the cognitive process by which humans infer the state of mind of others and anticipate their reactions. This complex skill relies on integrated information processing, including the perception of social cues gathered from faces, eyes, hands and body of others. Growing research indicates that early life exposure to neurotoxicant metals including lead and manganese is associated with maladaptive social behavior. Although promising, these findings have been based on self- and parent-reports of social behavior which suffer from response biases. While the value of collecting objective phenotyping measures along with surveys has long been recognized, the majority of large-scale community and population studies rely on survey reports of social behavior. In this costeffective and innovative proposal, we propose to use eye-tracking as an objective phenotyping tool for detecting environmentally associated changes in social cognition. Eye-tracking is a simple, rapid, non-invasive, sensitive and quantitative method enabling of recording spontaneous, unconscious gaze behavior towards socially relevant cues that provides insight into neural processing. We hypothesize that early life metal exposure adversely impacts social perception and that eye-tracking is a more sensitive assessment of environmentally-induced changes in neural connectivity. To test this, we leverage the PROGRESS study with existing longitudinal exposure and behavioral measurements and ongoing follow-up including high-resolution neuroimaging. We propose to add a recognized naturalistic eye-tracking paradigm of clips displaying peer-to-peer social interactions, and measure viewing time and number of fixations at the eyes, mouth, and faces of characters. We will examine associations between early life Pb and Mn exposure (in blood and teeth) and social cognition using eye tracking and parent-reported scale of social behavior. We will then investigate associations between early life metal exposure and intrinsic functional connectivity of the social brain. To our knowledge, no other study has attempted to investigate associations between similar aspects of social cognition, longitudinal assessment of early life metal exposure and high-resolution brain imaging.


Title of Project: Innovating Data Visualization Strategies for Tooth-Based Lead Report-Back

Principal Investigator: Sarah Evans, PhD, MPH

Co-Investigators: Manish Arora, BDS, MPH, PhD, FICD; Maida Galvez, MD, MPH; Alison Mears, AIA, Healthy Materials Lab, Parsons School of Design, The New School

Project Period: July 1, 2019 – June 30, 2020

Pilot Award Amount: $20,000

 

Abstract:

Reporting back biomonitoring data to study subjects has the potential to improve health literacy and promote exposure reduction behaviors. Technological advances in the field of exposure assessment allow for detection of biomarkers in novel matrices and measurement of multiple exposures across time, but resultant data is complex and clinical relevance is often uncertain. This poses unique challenges for communication of individual exposure data to study subjects in an understandable and meaningful way. Using methods pioneered in the Frank R. Lautenberg Laboratory for Environmental Health Sciences at Mount Sinai, we are able to reconstruct early life exposures to lead and other chemicals using deciduous teeth, contributing to our understanding of critical developmental periods during which organ systems are most susceptible to harm. This proposal seeks to develop effective strategies for reporting back individual child tooth lead data to families enrolled in birth cohort studies with the aim of promoting exposure-reduction behaviors. Given clinical uncertainty and the lack of normative data on tooth-lead levels, communicating results requires an innovative approach. To address these challenges, we will partner with students from the Parsons School of Design to create a novel, multi-modal strategy for reporting tooth lead levels to study subjects. This team science approach allows for cross-talk between environmental health scientists and data visualization and communication experts to create impactful public health messaging. Reports will include individual and aggregate tooth lead data, information about the health effects of lead exposure, and exposure reduction tips. Usability and efficacy of the developed materials will be tested in focus groups with English and Spanish speaking members of the East Harlem community. Feedback received will be used to modify the report-back strategy for future studies in which tooth lead data will be disseminated to participants in active birth cohort studies in the United States and Mexico.

Pilot Projects Awarded 2018

Title of Project: Manganese exposure, neuroimaging phenotypes, and gut-microbiome interactions: a pilot study

Principal Investigator: Cheuk Ying Tang, PhD

Co-Investigators: Roberto Lucchini, MD; Jianzhong Hu, PhD; Donatella Placidi, MD; Simona Fiorentini, MD; Andrea L. Deierlein, MPH, PhD; Megan Horton, PhD

Project Period: February 1, 2019 – January 31, 2020

Pilot Award Amount: $70,000

 

Abstract: Several ongoing studies are investigating the effects of environmental exposure to metals such as Manganese, lead and chromium on human cognition using brain imaging biomarkers and neuropsychological test batteries. In recent years an abundance of research has highlighted the important relationship between the brain and the gut-microbiome. The eubiosis of the gut-microbiome helps in digestion and general balance of neurotransmitters whereas a dysbiosis can lead to depression and other psychiatric conditions. There are limited reports on the effects of environmental toxins on the gut-microbiome. In this proposal we will analyze the relationship between microbiota composition, neuroimaging biomarkers and cognitive assessments in exposed and non-exposed subjects. To study these relationships we will analyze the gut-microbiome of the subjects that are part of one of our ongoing study: Public Health Impact of Manganese Exposure (PHIME). The PHIME study is currently in its second phase where neuroimaging biomarkers are being obtained using MRI. These subjects are from three well-characterized communities in Northern Italy that differ in the timing and intensity of environmental manganese exposure from current or historic ferromanganese alloy plant operations. Other readily available data on these subjects include neuropsychological assessments and extensive imaging scans. This proposal is to request funds to obtain fecal samples, perform sequencing and microbiome analysis. We will be able to leverage all the other readily available data as all collaborators on this application are also co-investigators of the PHIME study. The goal is to investigate the multidimensional relationships between exposure from early life to adolescence, cognition, imaging biomarkers, and the gut microbiome.


Title of Project: Metabolomics analysis to identify functional groups of multiple endocrine disruptor chemical exposures and their associations with childhood growth and development

Principal Investigator: Lauren Petrick, PhD

Co-Investigators: Susan Teitelbaum, PhD; Mary Wolff, PhD; Boris Reva, PhD

Project Period:  February 1, 2019 – January 31, 2020

Pilot Award Amount: $25,000

 

Abstract: Endocrine disruptor chemicals (EDs) have been associated with alterations in pubertal timing and somatic growth linked with breast cancer risk. However, investigations on the underlying disruptions of metabolic and biologic response pathways have not been undertaken. Furthermore, the effects of multiple ED exposures on pubertal outcomes during adolescence are unknown, even though exposures actually occur as integrated mixtures which may have profoundly different biological impacts as those investigated with a single exposure model. Using plasma from 171 girls in the Growing Up Healthy (GUH) cohort at Mount Sinai, we intend to identify metabolomic profiles associated with multiple exposure groups and outcomes. The GUH cohort is well characterized with over 30 exposure biomarkers and recall exposure data. Because many of the well-studied individual environmental chemical exposures have been found to have similarities in their biological function/activity, we propose to examine whether the combined effect of these similarly functioning chemicals, as multiple-exposure groups, can identify metabolites and mechanistic pathways associated with multiple real-life exposures. We are leveraging pilot funding (CHEAR PF08) for metabolomics analysis on 66 samples from this cohort, and will use this proposal for metabolomics analysis of an additional 105 samples (n=171). With this proposal we intent to 1) evaluate the feasibility of using multiple-exposure groupings to identify metabolomic biomarkers of ED exposure, 2) assess the viability of using these groupings to predict functionality, and 3) generate data on the relationship of identified biomarkers with somatic growth and age of menarche. This pilot data will be used to develop an R01/R21 emphasizing longitudinal metabolomics discovery during this important window of susceptibility of adolescent development in the expanded Breast Cancer and Environment Program (BCERP) national cohort of 1231 girls for whom we have comparable and harmonized data.


Title of Project: Prenatal time windows of vulnerability to interactions of phthalates and allostatic load among low-income women
Principal Investigator: Shelley H. Liu, PhD

Co-Investigators: Julie Spicer, PhD; Annemarie Stroustrup, MD

Project Period:  February 1, 2019 – January 31, 2020

Pilot Award Amount: $25,000

 

Abstract: Pregnancy is a vulnerable time for all women. But the stakes are even higher for low-income women, who are at greater risk of adverse infant outcomes such as preterm birth. A variety of factors likely contribute to this disparity. Here, we study how environment and stress interact across critical time windows of pregnancy to jointly impact infant outcomes for low-income women. Specifically, we study phthalates, a plasticizer ubiquitous to daily life, with higher exposures in low-income women, and linked to preterm birth. We hypothesize that short-term exposure to phthalates at critical time windows of pregnancy, coupled with long-term dysregulation of multiple inter-related physiological systems due to chronic stress (biologically manifested as allostatic load), can place certain pregnant women at greater risk of adverse infant outcomes. To our knowledge, the interaction of phthalates and allostatic load has not been studied. We capitalize on a new cohort – the Pregnancy, Stress and Infant Outcomes study (PreSIO; PI: Spicer, 5R00HD079668-04; n=68). PreSIO just began enrolling low-income pregnant women at the Mount Sinai Ambulatory OB/GYN practice (10 already recruited). Currently, no environmental exposures are collected in PreSIO; thus, it provides a unique opportunity to fulfill the P30 Center’s mission on increasing the environmental health research portfolio at Mount Sinai. In Aim 1, we collect phthalate metabolites at two prenatal windows (16-21 weeks, 22-29 weeks), and investigate time-varying and cumulative effects of prenatal phthalate exposure on infant outcomes (gestational age at birth, birthweight). In Aim 2, we develop a statistical method to model interactions of phthalate mixtures and allostatic load mixtures, and use it to investigate if allostatic load moderates the association between phthalates and infant outcomes. This pilot will lay the groundwork for future R21/R01 applications in line with NIEHS 2018-2023 Strategic Plan priorities, to study individual susceptibility to environment-stress interactions and reduce health disparities for low-income women.


Title of Project: Improving identification of home-based environmental exposures and social stressors in at-risk families in East Harlem: a community based participatory project
Principal Investigator: Elizabeth J. Garland, MD, MS

Co-Investigators: Erin Thanik, MD, MPH; Elizabeth Howard, MD; Carlos Melendez, PhD; Emily Moody, MD, MS; Luz Claudio, PhD; Maida Galvez, MD, MPH

Project Period:  February 1, 2019 – January 31, 2020

Pilot Award Amount: $25,000

 

Abstract: This project improves infrastructure and assessment tools at LSA Family Health Services (LSA), a community based organization in East Harlem, and integrates environmental health screening into assessment of high risk families. This community based participatory research project is aligned with the NIEHS Partnerships in Environmental Public Health mission of increasing impacts of emerging research by translating science into programs and policies that prevent and reduce exposures, particularly for high poverty communities who are disproportionately burdened by environmental exposures. With expert support of P30 faculty, input will be provided to LSA on enhanced data capture and management allowing us to work together to examine the association between environmental factors, social stressors and adverse child outcomes. The objectives are: 1) develop a database to capture social stressors and home environmental risks and health outcomes in families served by LSA, 2) identify gaps and redundancies in existing health assessment tools and 3) design an environmental assessment tool. We will conduct semi-structured interviews with LSA public health nurses on codifying anecdotes and client interactions into meaningful assessments, in-agency referral mechanisms and design interventions. We will attend a LSA mothers’ group to discuss environmental concerns and identify themes. Collaboration with LSA will inform new database development to ensure it meets needs for program evaluation and health outcomes research. The new database will be populated with retrospective data for data analysis.This project is innovative as it advances clinical practice of environmental risk identification to improve child health outcomes through enhanced assessment and sets the stage for improved home-based interventions.The innovation is in development of a home-environmental risk assessment tool that addresses gaps and further informs design of replicable home-based interventions. Ultimately, linking identified environmental risks with home-based interventions improves health outcomes while addressing social determinates of health,environmental health disparities and environmental justice.


Title of Project: Impact of maternal prenatal stress on composition and function of the infant microbiome

Principal Investigator: Rebecca Campbell, PhD

Co-Investigators:Chris Gennings, PhD; Andrea Baccarelli, MD, PhD (Columbia); Supinda Bunyavanich, MD

Project Period:  February 1, 2019 – January 31, 2020

Pilot Award Amount: $25,000

 

Abstract: Maternal prenatal psychosocial stress is common, especially in women of low socioeconomic status,with negative consequences for child neurocognitive development. How prenatal stress impacts child neurodevelopment, and why effects are often sex-specific, is not clear, but accumulating preclinical evidence points to the microbiome. An abnormal early-infancy intestinal microbiome can have long-term health consequencessimilar to those of prenatal stress, including immune and metabolic dysfunction and neurocognitive delays. Prenatal stress disrupts normal maternal microbiome shifts during pregnancy, impactingthe microbes that the infant receives at birth.Sex differences in the intestinal microbiome existin infancy and possibly even in the pregnant woman’s microbiome. Thus,the early-infancy intestinal microbiome may yield valuable new insights into intergenerational and sex-specific transmission of prenatal stress. We will investigate compositional and functional characteristics of the infant microbiome within an ongoing multiethnic urban cohort study with comprehensive, high-quality assessments of maternal stress. Stress exposures in pregnant women,including life stressors, trauma history and psychological function,are assessed with validated questionnaires,and hair cortisol measured.Childhealth outcomes including cognitive function are assessed frominfancy through mid-childhood. In this pilot, we will analyzestool samples from a subsample of cohort participants (n=50) at age two weeks, extracting bacterial DNA and RNA for 16S sequencing and transcriptomic analysis, respectively. Stress-associated differences in 16S gene diversity and composition and metagenome expression will be analyzed,and sex-specific effects examined. This proposed pilot will investigate the early-infancy intestinal microbiome as a novel propagator of prenatal stress effects on child health. We will generate preliminary data verifying the feasibility of detecting stress effects on the infant intestinal microbiome, which will support a future study of theroleof the infant intestinal microbiome in prenatal stress effects on child cognitive development. Additional prenatal co-exposures and child health outcomes could be investigated in the future.


Title of Project: Ambient air pollution, lipidomics, and overweight/obesity in an Italian adolescent cohort

Principal Investigator: Elena Colicino, PhD; Megan Niedzwiecki, PhD (Multi-PI)

Co-Investigators: Robert Wright, MD; Roberto Lucchini, MD; Itai Kloog, PhD; Massimo Stafoggia

Project Period: February 1, 2019 – January 31, 2020

Pilot Award Amount: $25,000

 

Abstract:In the last three decades, the prevalence of overweight and obesity in adolescents tripled. Currently, half of US adolescents are overweight or obese, and rates are increasing around the world, including Italy. Environmental conditions, including ambient air pollution (particulate matter with diameter ≤2.5 μm [PM2.5]), might contribute to the development of overweight and obesity. Air pollution exposure has been shown to affect cellular and systemic lipid processes and lead to abdominal adiposity in adults, but little is known about these relationships in adolescents.Adolescence is a critical developmental period in which the levels, compositionand metabolism of lipids undergo alterations due to major hormonal changes. We hypothesize that adolescents may be more susceptible to lipid perturbations by ambient air pollution. However, the limited availability of lipid biomarkers that reflect detrimental environmental exposures and predict early obesity risk limits opportunities for prevention and therapeutic interventions. To address this gap, we aim to identify novel lipidomic biomarkers that link long-­term exposure to PM2.5 with obesity. We will use plasma lipidomics—a characterization of lipid species, metabolic pathways and networks—to reveal environmentally-­driven alterations of lipid composition and abundance that underlie the onset and progression of adolescent obesity.Our overall goal is to determine whether long-­term exposure to PM2.5is associated with lipidomic alterations that contribute to overweight and obesity in adolescents. We will leverage the prospective Public Health Impact of Mixed element Exposure (PHIME) cohort of 665 adolescents (11-­21 years) living in the greater area of Brescia, Italy. We have daily measurements of PM2.5 since 2006. We will use advanced statistical methods to analyze lipidomics profiles in relation to (i) long-­term metrics of ambient PM2.5 and (ii) BMI, overweight,and obesity.

 

Pilot Projects Awarded 2018

Title of Project: High dimensional immune profiling of the response to prenatal air pollution
Principal Investigator: Cecilia Berin, PhD

Co-Investigators: Rosalind J. Wright, MD; Chris Gennings, PhD

Project Period: July 2, 2018 – July 1, 2019

Pilot Award Amount: $70,000

 

Abstract:Prenatal exposure to chemical (air pollution) and non-chemical (psychological) stressors have a negative  impact on child health including birth weight, neurodevelopment, and atopy/asthma. There is a lack of understanding of the mechanistic link between exposure and child health outcome. The immune system is thought to be a key mediator. Immune cells sense and respond to particulate matter (PM) or neuroendocrine signals, and immune processes are critical for diverse health outcomes including atopy, obesity, cardiovascular disease, and psychological function. Studies to date have measured selected serum biomarkers (C-reactive protein, IL-6) and tested for association with exposure. Alternatively, transcriptomics or epigenomics of placenta or cord blood has been performed. This provides the opportunity for discovery research, but provides no information on cell source or confirmation of protein expression. Multi-parametric approaches for immune profiling such as CyTOF provide the opportunity to quantify and phenotype all cells in peripheral blood simultaneously, at single cell resolution, and to examine a dynamic response to immune perturbation. This provides a much richer dataset that is more likely to convey functional changes that underlie susceptibility to immune-mediated disease. We propose to use the existing PRISM cohort to recruit 30 mother-infant pairs. Paired maternal blood and cord blood specimens will be obtained for immune profiling studies. The PRISM cohort collects detailed information on exposure to chemical and non-chemical stressors, including PM2.5. We will use CyTOF and Olink targeted immune proteomics to provide a detailed description of the immune system status at homeostasis and in response to immune and neuroendocrine stimulation. These studies will utilize  the Phenotyping and Environmental Modifiers Facility Core (Co-I Rosalind Wright) and the Biostatistics and Bioinformatics Facility Core (Co-I Chris Gennings). The data from this pilot study will be used to support a multi-PI R01 application to NIH PAR-18-333 (Understanding the Early Development of the Immune System).


Title of Project: Prenatal programming of the male vulnerability phenotype
Principal Investigator: Whitney Cowell, PhD

Co-Investigators: Rosalind J. Wright, MD; Jia Chen, ScD; Elena Colicino, PhD

Project Period: July 2, 2018 – July 1, 2019

Pilot Award Amount: $20,000

 

Abstract:Prenatal exposure to chemical (air pollution) and non-chemical (psychological) stressors have a negative  impact on child health including birth weight, neurodevelopment, and atopy/asthma. There is a lack of understanding of the mechanistic link between exposure and child health outcome. The immune system is thought to be a key mediator. Immune cells sense and respond to particulate matter (PM) or neuroendocrine signals, and immune processes are critical for diverse health outcomes including atopy, obesity, cardiovascular disease, and psychological function. Studies to date have measured selected serum biomarkers (C-reactive protein, IL-6) and tested for association with exposure. Alternatively, transcriptomics or epigenomics of placenta or cord blood has been performed. This provides the opportunity for discovery research, but provides no information on cell source or confirmation of protein expression. Multi-parametric approaches for immune profiling such as CyTOF provide the opportunity to quantify and phenotype all cells in peripheral blood simultaneously, at single cell resolution, and to examine a dynamic response to immune perturbation. This provides a much richer dataset that is more likely to convey functional changes that underlie susceptibility to immune-mediated disease. We propose to use the existing PRISM cohort to recruit 30 mother-


Title of Project: Lead Exposure and Kidney Function in Genetically Susceptible Ethnic Minorities: A Pilot Study (CBPR)
Principal Investigator: Girish Nadkarni, PhD

Co-Investigators: Robert Wright, MD; Andrea Baccarelli, MD, PHD (Columbia); Joel Schwartz, PHD (Harvard)

Project Period:  July 2, 2018 – July 1, 2019

Pilot Award Amount: $20,000

 

Abstract: Chronic kidney disease (CKD) affects up to 15% of the US population; persons of African ancestry (AAs) have threefold times the prevalence than people of European ancestry (EAs). Reasons for this disparity are multifactorial, and include genetic, socioeconomic, environmental and healthcare factors. Recent discoveries reveal that a significant proportion of this disparity is genetic. High risk Apolipoprotein L1 (APOL1) genotypes, found nearly exclusively in AAs are associated with a ten-fold higher risk of end stage renal disease (ESRD).2 However, only not all individuals with APOL1 highrisk genotype develop kidney disease, indicating suggesting a role for environmental modifiers. There is an established link between cumulative heavy metal exposure, particularly lead, and incidence and progression of CKD. There are also substantial disparities in lead exposure between AAs and EAs due to differing environmental exposures. This raises the interesting hypothesis that cumulative lead exposure and APOL1 genotype may interact (a gene-environment interaction) for the outcome of CKD. We propose to explore this hypothesis using the unique BioMe biobank and the resources of the Mount Sinai Transdisciplinary Center on Health Effects of Early Environmental Exposures. This study will be conducted in full partnership with our community board who have been conducting APOL1 research for 4 years, and have specific interest in gene-environment interactions, will be full partners in the conduct, analysis and dissemination of this study. This pilot study will allow us to explore the ‘second-hits’ needed for CKD to develop in persons with high-risk APOL1 genotype and generate valuable preliminary data and sample size needs for a grant proposal to more fully elucidate geneenvironmental influences on development of kidney disease and related racial-disparities in a much larger population. This may lead to improved insights, enabling us to target the persistent disparities in renal disease.


Title of Project: Effect of Gestational Exposure to Fine-size Particulate Matter 2.5 on Placental Gene Expression in Relation to Birth Weight
Principal Investigator: Jia Chen, ScD

Co-Investigators: Judith Zelikoff, PhD (NYU); Carmen Marsit, PhD (Emory)

Project Period:  July 2, 2018 – July 1, 2019

Pilot Award Amount: $20,000

 

Abstract: Numerous epidemiological and animal studies have demonstrated that exposure to ambient fine particulate matter <2.5um in diameter (PM2.5) during gestation is associated with adverse obstetric outcomes like preterm birth, intrauterine growth restriction and deviation from normal birth size. The placenta provides the crucial link between the intrauterine environment and fetal growth/development. We have previously demonstrated that dysregulation of gene expression in placenta was associated with abnormal fetal growth both under- and over-growth. However, how the placenta genome responds to environmental stimuli, such as PM2.5, is much less known. The present study aims to investigate causal relationships between PM2.5 exposure and changes in the placental transcriptome and whether disruption of the transcriptome is subsequently linked to changes in birth weight (BW). We will employ a hybrid study design combining a mouse model and a population study. First, the placental transcriptome from mice exposed to concentrated ambient PM throughout the full term of gestation will be profiled by RNAseq; co-expression gene networks will be constructed by weighted gene co-expression analysis (WGCNA). The PM2.5 -responsive genes in the mouse model will be validated in human placentas obtained from the Rhode Island Child Health Study (RICHS), a population-based birth cohort, using RT-PCR. We will also evaluate how placental gene expression mediates the association between maternal PM exposure and BW in the RICHS. Understanding the mechanisms by which PM2.5 alter the placental transcriptome leading to abnormal growth is invaluable in developing interventions to offset the impact of exposure.


Title of Project: Does study participation and receiving feedback on her child’s EDC exposure alter mother’s risk perception and behavior?
Principal Investigator: Sarah Evans, PhD

Co-Investigators: Shanna Swan, PhD; Emily Barrett, PhD; Katrina Korfmacher, PhD

Project Period:  July 2, 2018 – July 1, 2019

Pilot Award Amount: $20,000

 

Abstract: Perception of risks posed by environmental exposures influences behaviors that affect those exposures. Interventions that modify risk perception should therefore lead to behaviors that result in reduction of potentially harmful exposures. In this pilot study we will investigate whether participation in The Infant Development and Environment Study (TIDES), a multicenter prospective birth cohort study designed to assess associations between phthalate and other chemical exposures and child development, modifies environmental risk perception and behaviors and whether mother’s behaviors impact child phthalate exposures. We will also explore whether knowledge of one’s child’s urinary phthalate levels increases behaviors that have the potential to reduce exposure. 50 subjects will be randomly selected from families enrolled in the TIDES study at University of Rochester Medical Center who completed a first trimester environmental risk survey and whose child provided urine at age 4 and asked to complete the same survey they completed during pregnancy. Half of subjects will be given their child’s 4-year urinary phthalate metabolite levels plus aggregate data from the pilot cohort, and half will receive aggregate data only. All subjects will receive information on phthalate health effects and exposure reduction strategies. After three months, subjects will be re-surveyed about their attitudes and behaviors towards environmental risk and pre- and post-intervention responses compared. Responses given before the receipt of phthalate data will be compared to responses given during pregnancy. We hypothesize that perception of risk and frequency of exposure-reduction behaviors will have increased since pregnancy, in part due to continued participation in TIDES and that knowledge of child phthalate exposure will lead to a further increase in exposure-reduction behaviors. Findings from this pilot will be used to improve the usability and efficacy of biomonitoring report-back methods and provide pilot data to support a R21 application to expand this study to the entire TIDES cohort.


Title of Project: Lead exposure during pregnancy, serum metabolomics, and postpartum
depression
Principal Investigator: Megan Niedzwiecki, Lauren Petrick (Multi-PI)

Co-Investigators: Robert Wright, MD; Elena Colicino, PhD

Project Period:  July 2, 2018 – July 1, 2019

Pilot Award Amount: $20,000

 

Abstract: Lead (Pb) exposure is associated with detrimental health effects, even at low levels. While the neurotoxiceffects of Pb exposure during pregnancy have been widely studied in children, the neurotoxicity of Pb during this critical window in mothers is not well delineated, especially in postpartum depression (PPD), a serious mental condition affecting 10-­20% of new mothers. Further, there remains a great need to identify novelbiomarkers of Pb exposure to better understand mechanisms of Pb-­mediated toxicity. The application of untargeted high-­resolution mass spectrometry (HRMS), in which thousands of metabolites are simultaneously measured in a biospecimen, holds great promise for this task, but challenges in HRMS metabolite identification have restricted the widespread application of HRMS in epidemiological studies. We expect that employing an integrated approach to identify the biological response to Pb exposure with HRMS will uncover novel metabolites and/or metabolic pathways associated with Pb toxicity and PPD risk. To address this, we first propose a novel bioinformatics workflow for metabolite identification of untargeted HRMS data in which MS1-­based accurate mass identifications are paired with MS2 data-­independent acquisition (DIA), which will improve the speed and accuracy of annotation. This method will be integrated into the Integrated Health Sciences Facility Core (IHSFC) Lab methods for use in future Center studies and distributed to the public. Second, we will identify metabolomic signatures of prenatal Pb exposure in serum
samples collected during the 2nd and 3rd trimesters from mothers enrolled in the Programming Research on Obesity, GRowth, Environment and Social Stress (PROGRESS) cohort in Mexico City, a region with a wide range of Pb exposures. Identifications of Pb-­associated metabolites will be aided by our MS1/DIA approach. Further, we will look for metabolomics signatures of PPD diagnosed 6 months and 1 year postpartum, as well as associations of Pb and Pb-­associated metabolites with PPD.


Title of Project: Structural and functional brain imaging in ferromanganese workers to assess the impact of manganese exposure on neurophenotypes from early life to adulthood

Principal Investigator: Roberto Lucchini, MD

Co-Investigators: Robert Wright, MD; Cheuk Tang Ying, PhD; Megan Horton, PhD; Elena Colicino, PhD; Donatella Placidi, MD; Roberto Gasparotti, MD

Project Period:  July 2, 2018 – July 1, 2019

Pilot Award Amount: $20,000

 

Abstract:Cognitive functioning can be impacted by exposure to neurotoxicants occurring from early life to the old age, with major public health implications. Manganese exposure can cause cognitive impairment in early life and memory dysfunctions in adults, by targeting critical brain areas including frontal and parietal cortex, and the caudate nucleus in the striatum. High quality neuroimaging tools provide insights on the structural and functional changes associated with environmental exposures. In this proposal we will assess cognitive functioning in workers with lifetime exposure to manganese and other metals, and with extensive longitudinal air monitoring data, biomarkers and neurofunctional testing. Structural and functional brain magnetic resonance imaging will be used to assess the association of cumulative exposure with the neuroimaging phenotypes. Functional cognitive assessment will be also piloted, using MoCA (Montreal Cognitive Assessment), CogState and novel testing batteries, such as the NIH toolbox, to examine the association with the neuroimaging phenotypes. The presence of amyloid deposition will be tested using PET scan, as a highly innovative exploratory aim. To our knowledge this is the first study exploring β-amyloid brain deposition as a predictor of clinical neurodegenerative disease in manganese exposed individuals. Teeth will also be collected from the workers to assess lifetime and exposure and different exposure windows through laser ablation ICPMS analysis. With this proposal, we will leverage the existence of the multiple cohorts of the PHIME (Public Health Impact of Metal Exposure) study, which includes different age groups residing in the same impacted areas in Italy, and extend our current imaging studies on adolescents to the adult workers’ cohort. This pilot study will yield preliminary data for larger grant applications, which will further increase the available data of the PHIME study on metal exposure and neurological impacts from early life to the old age.


Title of Project: Metal exposure, Brain Autoantibodies in pregnancy and child
neurodevelopment

Principal Investigator: Uri Laserson, PhD; Elena Colicino, PhD (Multi-PI)

Co-Investigators: Robert Wright, MD

Project Period:  July 2, 2018 – July 1, 2019

Pilot Award Amount: $20,000

 

Abstract:The role of neuroimmunology and anti-brain autoantibodies in the pathogenesis of developmental disorders such as autism and schizophrenia has recently become a topic of intense interest. Concurrent to this work, neurotoxic metals such as lead and mercury have been linked to these diseases, as well as to the development of anti-brain autoantibodies. Despite these hints in the literature, no prior study has prospectively assessed lead and mercury exposure in pregnancy, linked them to the development of autoantibodies nor determined whether this represents a mechanistic pathway explaining the metals’ neurotoxicity. In this proposal we will use the phage immunoprecipitation sequencing (PhIP seq) assay to comprehensively measure antibodies against all possible autoantigens in maternal serum collected during pregnancy in the PROGRESS longitudinal birth cohort. We will test associations of these autoantibodies with blood lead and mercury exposure as well as with measures of executive function and IQ in children between ages 4-6. PROGRESS has been ongoing since 2007, and all neurobehavioral data and necessary biosamples already exist, rendering this study highly cost- and time-efficient. Data generated through this project will serve for both future publications and, most importantly, for a future R01 proposal expanding these measures to multiple time points and testing the relationship with metal mixtures. The multi-PI’s are early stage investigators with expertise in immunology and biostatistics. The proposal uses all 3 facility cores of the P30 Center as well.

Pilot Projects Awarded 2017

Title of Project: “Air Pollution Exposure During Pregnancy and Sleep Health in Childhood”
Principal Investigator: Sonali Bose, MD MPH

Co-Investigators: Rosalind J. Wright, MD

Project Period: October 2017 – September 2018

Pilot Award Amount: $50,000

 

Abstract: In utero exposure to ambient air pollution may have adverse effects on fetal growth and development, increasing the risk of a variety of health disorders in childhood. Using novel hybrid satellite- and ground-based exposure methods to estimate daily pollutant exposures at high spatial resolution in a longitudinal birth cohort, we have previously demonstrated that exposure to particulate air pollution during specific periods of gestation is linked to adverse respiratory and neurocognitive outcomes in childhood, potentially through mechanisms involving immune, inflammatory, and autonomic pathways. However, less is known regarding the direct influence of prenatal air pollution upon sleep quality in children, which may occur through similar inflammatory or autonomic processes. While limited epidemiologic studies do suggest that airborne pollutant exposures are associated with alterations in sleep patterns in several populations, none have specifically examined the early life period, when sleep is most critical for growth and development. Indeed, inadequate sleep has already been linked to a range of health problems in childhood and later life, highlighting the need for a better understanding of environmental risk factors for altered sleep in early childhood. We propose a feasibility pilot, in which we will leverage our existing prenatal pollutant exposure models and ongoing longitudinal birth cohort to determine optimal methods of assessing sleep in a subset of preschool children. Within the parent study, we will add subjective and objective measurements of sleep variables through validated questionnaires, 24-hour accelerometers, and EEG-based polysomnographic testing, as well as in-home measures of autonomic function (e.g. low-frequency heart variability and respiratory sinus arrhythmia) during sleep, to inform a larger study powered to examine associations between sleep patterns and air pollution. Ultimately, we predict that children with higher prenatal particulate matter exposure will have reduced sleep duration, increased sleep disturbances, and/or heightened autonomic dysfunction, compared to less exposed children.


Title of Project: Biomarkers of Lead Exposure and a Novel Form of DNA Methylation in the Human Genome
Principal Investigator: Gang Fang, PhD

Co-Investigators: Robert Wright, MD; Andrea Baccarelli, MD, PHD (Columbia); Joel Schwartz, PHD (Harvard)

Project Period: October 2017 – September 2018

Pilot Award Amount: $50,000

 

Abstract: DNA methylation at 5-methylcytosine (5mC) is a well-known epigenetic mark that regulates gene expression. Recent research by our group identified N6-methyladenine (N6mA) in human DNA as a newly discovered epigenetic mark that also regulates gene expression, in particular transposable element expression. There is a growing interest in the role of transposable elements in predicting health effects as their expression would induce predictable cellular toxicity. Increasing evidence suggests that changes in methylation of the transposable element LINE-1 (L1) secondary to environment exposures may have significant impacts on health. Thus L1 expression and its epigenetic marks have great potential for the development of novel epigenetic biomarkers. Our lab recently contributed to the discovery of N6mA in mouse genome, while also demonstrating that it is over represented in regulatory regions of L1s. Before this study, the prevailing dogma was that N6mA exclusively occurs in unicellular organisms. Since this breakthrough, our lab has been leading the genome-wide N6mA mapping in humans revealing that N6mA events are enriched at L1s. This exciting discovery motivated this application, in which we aim to achieve three milestones. First, we will examine the whether N6mA methylation at L1 is responsive to environmental exposures by quantifying their relationship with lead exposures rigorously measured in bone and blood in multiple cohorts at different life stages. Lead is a paradigm toxicant and has already been shown to alter 5mC levels in L1 making it a logical starting point for this work. Second, we will characterize the relationship between the two forms of DNA methylations (N6mA and 5mC) in their joint association with lead exposure. Third, to discover more precise biomarkers, we will develop a genomics method that can simultaneously map N6mA and 5mC events on individual L1s in order to perform high- resolution association analysis between both forms of methylations and lead exposure.


Title of Project: Development of a novel genome-wide method for mapping UV-induced DNA lesions
Principal Investigator: Aneel Aggarwal, PhD

Co-Investigators: Gang Fang, PhD

Project Period: October 2017 – September 2018

Pilot Award Amount: $20,000

 

Abstract: Exposure to UV radiation is a major detriment to human health. However, despite the known etiological effects of UV exposure, methods for detecting initial UV-DNA damage and the mutational processes that follow are severely limited. There is an urgent need for a high-throughput method that can directly detect UV-DNA damage at the genome level in human cells. Our long-term goal is to develop a method that will permit direct detection of UV radiation-damaged DNA bases at a single nucleotide resolution based on damaged DNA immunoprecipitation (DDIP) followed by single-molecule, real-time (SMRT) DNA sequencing. The development of the method depends critically on the ability to enrich for damage- containing genomic DNA fragments. We propose here a method based on the use of bacteriophage T4 endonuclease V (EndoV) to enrich for UV-damaged DNA. Specifically, DNA from melanocytes exposed to UV radiation will be isolated, sheared, and enriched for UV-induced lesions by EndoV. A catalytically deficient mutant (E23Q) of EndoV will be expressed, purified, and conjugated with magnetic beads for pull- down of DNA fragments containing UV-induced lesions. These enriched DNA fragments will be directly used for SMRT DNA sequencing of both strands for detection of DNA lesions based on the kinetic “signature” that we have already derived. The development of DDIP-SMRT seq will have a major impact on our ability to directly assess the effects of UV-radiation and other environmental DNA damaging agents on cellular DNA and will form the basis of an R01 application to NIEHS.


Title of Project: Exploring Transcriptome and Endocrine Effects of Glyphosate-based Herbicides in Early Life
Principal Investigator: Corina Lesseur, MD, PhD; Jia Chen, ScD (Multi-PI)

Co-Investigators: Susan L Teitelbaum, PhD

Project Period: October 2017 – September 2018

Pilot Award Amount: $20,000

 

Abstract: Glyphosate is the most commonly used herbicide worldwide. Human exposures to glyphosate-based herbicides (GBHs) are rising rapidly as their presence in water and food grows. There is significant controversy regarding the safety of GBHs due to conflicting findings. Most of the current knowledge comprises studies performed in adults with particular focus on cancer; little data exist on potential effects of GBHs in children and on non-cancer outcomes. Moreover, traditional risk assessment studies have not interrogated GBHs as complex chemical formulations (e.g., Roundup® weed killer) that could be more toxic than glyphosate alone. Thus, there is an impending need to investigate possible health-related effects of chronic exposure to low-level glyphosate alone and GBH formulations especially during highly susceptible windows of development from the in utero period to early adulthood. We hypothesized that chronic low-level exposure to glyphosate or Roundup® during fetal development through early adulthood results in detectable changes in the transcriptome of multiple target tissues (brain, kidney and liver) as well as imbalances of plasma pituitary hormones. We will leverage banked samples from an existent study that exposed Sprague-Dawley rats to glyphosate or Roundup® through drinking water from gestation day 6 to post-natal day 70. The exposure dose used, 1.75mg/kg bw/day, is relevant to human exposure levels and corresponds to the “acceptable daily intake” (ADI) for glyphosate in the US. Our approach has multiple strengths: 1) we will obtain information on multiple tissues and endocrine markers to assist on a comprehensive evaluation of GBHs safety; 2) we will evaluate the effects of glyphosate and GBH exposure using a relevant dose during a sensitive exposure window.


Title of Project: Examining windows of vulnerability for prenatal heavy metal programming of infant autonomic function

Principal Investigator: Ashley J Malin, PhD; Rosalind Wright, MD, MPH (Multi-PI)

Co-Investigators: Ghalib Bello, PhD

Project Period: October 2017 – September 2018

Pilot Award Amount: $20,000

 

Abstract:Heavy metal exposures have been linked to autonomic dysfunction and consequent cardiovascular risk in adults. However, the effects of such exposures on the developing autonomic nervous system (ANS) are less understood. Therefore, in the current study we aim to examine the impact of prenatal heavy metal exposure on infant cardio-respiratory functioning. Additionally, in testing this relationship we aim to identify windows of vulnerability for heavy metal programming of infant autonomic function. In addition, maternal prenatal stress has been linked with infant ANS programming. Therefore, we will also explore whether maternal stress modifies effects of prenatal heavy metal exposures on infant ANS functioning.

We will measure a panel of metals (including: arsenic, lead, mercury, cadmium, aluminum, manganese, chromium and cobalt) in maternal hair at delivery using novel methods that reconstruct exposure over gestation implemented using laser ablatation inductively coupled plasma mass spectrometry (LA-ICP-MS). Additionally, we will validate hair metal biomarkers against metal levels in maternal whole blood at 26-28 weeks gestation. LA-ICP-MS provides weekly exposure estimates over pregnancy. It will be coupled with data driven statistical methods to identify windows of vulnerability by testing the relative impact of heavy metal exposures at different prenatal time points on infant ANS function (assessed at rest and during an in-laboratory stressor at 6 months) using the BioRadio Wireless Physiology Monitor (Great Lakes NeuroTechnologies, Cleveland, OH). Analyses will consider ANS parameters including respiratory sinus arrhythmia (RSA, uncorrected and corrected for respiratory rate and tidal volume), and T-wave amplitude (TWA). Maternal lifetime stress will be measured using the Life Stressor Checklist Revised (LSC-R) administered prenatally.

We expect our findings to enrich our understanding of early life environmental factors that contribute to ANS dysfunction. Furthermore, we anticipate that the invaluable information obtained regarding windows of vulnerability will have important implications for prevention and treatment of cardiorespiratory disorders


Title of Project: Development of Placental Cell Culture System to Test Metal Mixture- Induced Perturbations in Placental Function
Principal Investigator: Maya Deyssenroth, DrPH; Jia Chen, ScD (Multi-PI)

Co-Investigators: Chris Gennings, PhD; Ke Hao, ScD

Project Period: October 2017 – September 2018

Pilot Award Amount: $20,000

 

Abstract: Using a systems biology approach, we recently delineated the transcriptome-wide gene network and identified unique network modules, enriched for genes involved in gene expression and metabolic hormone secretion, in the human placenta. We also reported perturbations of some of these modules in fetal growth restriction. Concurrent efforts are also being made to develop innovative means to integrate whole-genome network data and exposure data to discover novel loci linking environmental exposures to health outcomes.
Using weighted quantile sum (WQS) regression analysis, we identified several placenta gene modules that are susceptible to metal exposure predominated by arsenic and cadmium (As/Cd). However, biological verification of these empirical observations is urgently needed to validate the in silico approach and to offer insight into the underlying biologic mechanism. In this pilot study, we propose to develop an in vitro placenta cell culture system to assess network-derived hub gene expression changes in response to As/Cd exposure, assess As/Cd induced changes in placental phenotypes, including proliferation, migration and invasion, and measure As/Cd induced changes in metabolic hormone secretion. The successful development of a placental cell culture system has the potential to be leveraged in additional P30 studies assessing the influence of environmental agents on placental biomarkers.


Title of Project: MY NYC AIR: Environmental Health Citizen Science (CBPR)
Principal Investigator: Maida Galvez, MD, MPH

Co-Investigators: Nancy Loder Jeffery, RN, MPH (NYCDOHM); Grant Pezeshki, MS (NYCDOHM); Carol M. Horowitz, MD, MPH

Project Period: October 2017 – September 2018

Pilot Award Amount: $20,000

 

Abstract: Air quality in New York City has improved over the past several decades, but concentrations of multiple air pollutants remain at harmful levels, particularly for seniors, children, and those with pre-existing health conditions. Objective: We aim to establish meaningful collaborations between local government agencies, academic and medical institutions, and community groups to enhance the capacity of at risk communities to proactively identify local sources of outdoor air pollutants in high risk NYC neighborhoods that often suffer from a disproportionate burden of environmental exposures. Methods/Innovation: Together with diverse stakeholders, we plan to pilot the air quality app “My NYC Air”, developed by the NYC Department of Health and Mental Hygiene in collaboration with technology consultants (Mount Sinai App Lab) to conduct the necessary user interface testing needed prior to publicly launching. This work will help inform the type and quality of data that could be collected, determine methods to best manage crowdsourced data, and will allow us to refine analysis and visualization techniques needed for effectively communicating crowd-sourced data. Use of “MY NYC Air” literally places the ability to collect air quality concerns at people’s fingertips, through use of their smartphones which are now in routine use by families of diverse socioeconomic backgrounds. Significance: “My NYC Air” has the potential to increase citizen participation in acquiring, interpreting and communicating air quality data, which can inform community based organizations, clinicians, researchers, public health officials and policy-makers on air quality issues as identified by NYC residents.


Title of Project: Statistical methods to assess prenatal exposures to metal mixtures and associations with latent patterns of neurodevelopmental trajectories
Principal Investigator: Shelley H. Liu, PhD

Co-Investigators: Qixuan Chen, PhD, MS; Brent Coull, PhD; Chris Gennings, PhD; Robert Wright, MD

Project Period: October 2017 – September 2018

Pilot Award Amount: $18,000

 

Abstract: Neurodevelopmental delay is a complex public health problem, affecting up to 15% of children in the general population. As genetic factors only explain a small percentage of these delays, environmental factors likely play a larger role. Prenatal exposures to metal mixtures, such as lead and arsenic, can potentially injure the fetal brain. Accordingly, the NIEHS has prioritized the study of both complex chemical mixtures and early childhood neurodevelopment. Typically, studies of metal mixtures and neurodevelopment use models that assume metals impact each child’s health to the same degree. In reality, there may be latent, or underlying, population subgroups of infants with distinct neurodevelopment trajectories over time, and the impacts of exposure to metal mixtures may differ across these subgroups. To our knowledge, studies have not addressed if infants in latent classes with distinct neurodevelopmental trajectories – particularly those in the delayed latent class – are differentially vulnerable to metal mixtures, and if interactions among the metal mixture components differ across latent classes. If we identify subpopulations with greater vulnerability to mixtures, we can potentially help public health practitioners target early interventions.
We propose to develop a two-stage statistical model to investigate these questions, and conduct a secondary data analysis of the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) prospective cohort study. PROGRESS contains extensive data on prenatal exposures to metal mixtures, and neurodevelopment assessed through the Bayley Scales of Infant and Toddler Development measured over time. Our two-stage model will first use growth mixture modeling to identify latent classes of infants with distinct patterns of neurodevelopmental trajectories. Second, we will separately study each latent class, using a flexible Bayesian approach to model how metal mixtures, and their interactions, are associated with neurodevelopmental trajectories. We will create an R package for researchers to implement this two-stage model for other datasets.