Pilot Projects Awarded 2019

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.