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.