2024 HEALS Pilot Program Awardees Announced

Thyroid cancer incidence has increased steadily over the past decades, which can only be partially explained by increased use of high quality diagnostic imaging. We therefore hypothesized that exposome factors may play a role in thyroid cancer etiology. Through our previously funded P30 pilot study, we investigated the association between thyroid cancer and per- and polyfluoroalkyl substances (PFAS), also known as “forever chemicals”, a group of persistent environmental pollutants used in industry and consumer products since the 1940s. We found a significant 56% increased rate of thyroid cancer diagnosis per doubling of linear perfluorooctanesulfonic acid (nPFOS) intensity. Additionally, we were the first to explore time between exposure and thyroid cancer diagnosis, demonstrating a potential role of PFAS exposure in both thyroid cancer disease initiation and promotion.

The objective of this proposal is therefore to expand on these findings and investigate the interrelations between PFAS exposure, pathologic, and epigenetic markers of thyroid cancer, using available thyroid cancer tissue in the Mount Sinai Biorepository and Pathology Core of the thyroid cancer patients included in our initial nested case-control study (n=40) thus exploring potential carcinogenic pathways. Pathologic markers (aim 1) and epigenetic profiles (aim 2) will be compared between the high versus low PFAS exposure group, using the metabolomics results of our previous study.

This proposal is the logical follow-up study of our previously funded P30 pilot study linking the metabolomics results of our prospective study using Mount Sinai BioMe plasma samples with pathology samples from the Mount Sinai Biorepository. This will be the first study to investigate pathologic and epigenetic pathways associated with PFAS exposure in humans, which will generate crucial preliminary evidence for larger studies and is an important step in developing personalized treatment strategies in thyroid cancer care.

Prenatal metal/metalloid exposures are linked with adverse childhood neurodevelopmental outcomes and neuropsychological functioning in women. Nonessential metals generate reactive oxygen and deplete antioxidants, have endocrine disrupting properties, and impact immunomodulation to interfere with cellular processes involved in brain maturation and functioning, while essential micronutrients such as iodine can act as antioxidants and through other mechanisms to protect against metal toxicity. Iodine is essential for the synthesis and regulation of thyroid hormones which play vital roles in neurodevelopment and functioning with both very low and excessive iodine intake linked to low maternal-fetal thyroid hormone levels and adverse outcomes in women and children. At optimal levels, iodine also acts as an antioxidant and anti-inflammatory agent. Thus, optimal iodine status in pregnant women may mitigate the negative effects of toxic metals/metalloids on neuropsychological outcomes. Quantifying prenatal iodine status remains challenging. Many studies use dietary intake derived from food frequency questionnaires (FFQs) or urinary iodine concentration(UIC- a population surveillance measure); however, both are subject to misclassification, reflecting levels from recently consumed food. Measures of longer-term cumulative iodine status may be a better predictor of a women’s health and child outcomes. During pregnancy, iodine is stored in the placenta in a concentrationdependent manner serving as a storage supply to meet the needs of the developing fetus and mother.

To our knowledge, no epidemiological study has examined associations among prenatal exposure to a metal mixture, placental iodine stores, and neuropsychological outcomes in women and their children. We will examine independent associations between placental iodine concentrations and how cumulative placental iodine stores modify the effects of prenatal exposure to toxic metal/metalloids on perinatal depressive symptoms in women and infant temperament domains. We hypothesize that this association may be non-linear given that both inadequate and excessive iodine status has been associated with more detrimental neuropsychological effects.

Prenatal metal/metalloid exposures are linked with adverse childhood neurodevelopmental outcomes and neuropsychological functioning in women. Nonessential metals generate reactive oxygen and deplete antioxidants, have endocrine disrupting properties, and impact immunomodulation to interfere with cellular processes involved in brain maturation and functioning, while essential micronutrients such as iodine can act as antioxidants and through other mechanisms to protect against metal toxicity. Iodine is essential for the synthesis and regulation of thyroid hormones which play vital roles in neurodevelopment and functioning with both very low and excessive iodine intake linked to low maternal-fetal thyroid hormone levels and adverse outcomes in women and children. At optimal levels, iodine also acts as an antioxidant and anti-inflammatory agent. Thus, optimal iodine status in pregnant women may mitigate the negative effects of toxic metals/metalloids on neuropsychological outcomes. Quantifying prenatal iodine status remains challenging. Many studies use dietary intake derived from food frequency questionnaires (FFQs) or urinary iodine concentration(UIC- a population surveillance measure); however, both are subject to misclassification, reflecting levels from recently consumed food. Measures of longer-term cumulative iodine status may be a better predictor of a women’s health and child outcomes. During pregnancy, iodine is stored in the placenta in a concentrationdependent manner serving as a storage supply to meet the needs of the developing fetus and mother.

To our knowledge, no epidemiological study has examined associations among prenatal exposure to a metal mixture, placental iodine stores, and neuropsychological outcomes in women and their children. We will examine independent associations between placental iodine concentrations and how cumulative placental iodine stores modify the effects of prenatal exposure to toxic metal/metalloids on perinatal depressive symptoms in women and infant temperament domains. We hypothesize that this association may be non-linear given that both inadequate and excessive iodine status has been associated with more detrimental neuropsychological effects.

Per- and polyfluoroalkyl substances (PFAS) comprise a class of ubiquitous chemicals commonly found in everyday products. Previous research of our team showed that PFAS exposure may contribute to infertility in young women. However, the underlying mechanisms are not well understood, and evidence is limited in Singapore and other Asian populations who have high infertility rates. PFAS-induced inflammation may be a mechanism underlying these associations as supported by experimental evidence, but this hypothesis is not yet corroborated in humans. Therefore, we propose to test inflammation as a mechanism underlying the PFAS association with infertility by leveraging data from a unique, well-characterized, longitudinal, population-based cohort of generally healthy Asian women followed over a year while naturally trying to conceive. We propose to use state-of-the-art proteomics approaches to assess the associations between exposure to PFAS mixtures and inflammation-related proteins and corroborate inflammation as a potential pathway underlying adverse PFAS and infertility outcomes in women (Aim 1). We will further generate preliminary data examining the potential modifying role of genetic variants in the PFAS associations with inflammation and infertility (Aim 2). For this purpose, we will measure proteomics (OLINK Explore 384 Inflammation Panel) in plasma samples collected from 176 women at preconception in which PFAS, genomics, and other relevant covariates have already been measured. Findings may inform more effective interventions to prevent infertility and improve reproductive health, especially for Asian women who are disproportionally affected. Results from the present analyses will provide support to a larger K99/R00 proposal that will integrate proteomics and other omics biomarkers to elucidate potential biological pathways underlying the PFAS association with infertility in this same cohort.

The Metropolitan Transportation Authority (MTA) is reconstructing and expanding the Jamaica Bus Depot in Queens. This project will modernize the depot and provide the facilities needed to operate, maintain, and store up to 300 buses. Since the reconstruction will take place in 27 households backyards between 2025 and 2028, their lives will be directly affected. A 17-foot temporary easement will be taken by the MTA, and many residents will suffer a loss of their property without proper compensation. The reconstruction of the Jamaica Bus Depot offers a vital opportunity to assess and mitigate air quality impacts while fostering environmental justice and community involvement in environmental monitoring. Using a community-based participatory research approach (CBPR), researchers and residents will work together to develop impactful research for environmental justice. During the bus depot’s reconstruction between 2025 and 2028, our interdisciplinary team will deploy low-cost air sensing and pollution capture technologies to monitor emissions closely.

As part of this project, our aims include 1) integrating anti-racism and environmental justice frameworks into our training and research methodologies to develop the capacity of community members and researchers to participate in CBPR and 2) deploying low-cost air sensors and Carbon/Particulate Matter Capturing technology to monitor and mitigate the air quality impacts of the Jamaica Bus Depot reconstruction. Furthermore, the project will develop strategies for community mobilization, aiming to establish a sustainable model for environmental health governance that can be replicated in similar environmental justice communities throughout NYC.

Despite infrastructure designed to withstand severe weather, climate events increasingly exceed local adaptation thresholds for populations and infrastructure, causing health impacts. People who rely on electrical technology such as respiratory, mobility, and dialysis devices are largely elderly and particularly vulnerable to the compounding effects of climate emergencies and infrastructure failure; yet health systems are not equipped to predict or prepare for healthcare needs in this vulnerable group during climate emergencies, in part because of a lack of research and methods estimating the impact of climate emergencies in vulnerable groups such as the elderly.

We will use spatiotemporal comparisons to (1) identify localities which experience significant increases in health system demand during distinct climate emergencies, (2) understand all-cause and cause-specific healthcare utilization across the spectrum of unplanned care, and (3) model the contribution of technology dependence to healthcare utilization during climate emergencies. Our global hypotheses are that technology-dependent, particularly elderly, patients are a uniquely vulnerable group during climate emergencies and that accurate spatiotemporal modelling of their climate-related risk can be leveraged to increase health system readiness.

First, we will use national weather data to select local climate emergencies (heat wave, extreme cold, air pollution, and cyclone) within four states with disparate climates. Then, we will use comprehensive inpatient and emergency department discharge abstracts and case-crossover temporal comparisons to model all-cause and diagnosis-specific utilization during and after each climate emergency in the affected localities, identifying areas that experienced increased demand due to each climate emergency. Finally, we will model the contribution of technology dependence to climate emergency health system demand using Medicare data, stratifying by age, i.e., decade of life over 65. Methods developed will contribute to an ongoing program of climate-informed health services research focusing on vulnerable populations. Results will include actionable estimates which can be applied to increase health system readiness for climate emergencies.

Cleaning products and disinfectants (CP&D) use has been associated with adverse health outcomes such as respiratory and skin disorders in professional cleaners. Our research team identified that in general in NYC, Quaternary Ammonium Compounds (QACs) and sodium hypochlorite (bleach) are among the most common ingredients in CP&D. The COVID-19 pandemic has led to changes in cleaning and disinfection practices, and more specifically to both an increase in the use of CP&Ds and frequency of cleaning. For this reason, there is concern about potential exposures and their impact on the health of those occupational exposed as well as consumers in general. Very few studies have evaluated the exposure to CP&Ds among housecleaners in the US. Particularly because housecleaners are predominantly Latinx immigrants and a hard-to-reach population.

The Safe and Just Cleaners project, a community-based participatory research partnership, is one of the few studies that aimed to evaluate exposures to improve housecleaners’ working conditions and safety. Participants of this study, mostly Latinx immigrants, are particularly vulnerable due to inadequate working and employment conditions, lack of knowledge and limited access to safer products. In this proposal, we aim to leverage the well-established Safe and Just Cleaners project by implementing a case-control study and we propose to evaluate the use and exposures to CP&Ds and health symptoms by applying mixed-methods (biological monitoring to disinfectants, questionnaires, respiratory tests and microbiome measures) in New York City Latinx populations. This novel linkage of survey-based and biological estimates of exposure to cleaning products will improve exposure metrics for their association with health effects. Once established these measures may be used in epidemiologic studies and clinical assessments among cleaning workers. The results from this study will help develop preventive programs to improve the health and safety of Latina housecleaners in NYC.

There is currently limited knowledge on the impact of occupational exposures on the development of breast cancer. A deeper understanding of this significant and largely modifiable part of one’s environment is imperative. Our goal is to examine the associations between work and breast cancer among women enrolled in the Long Island Breast Cancer Study Project (LIBCSP), an existing population-based case-control study.

Using questionnaire-based data from the LIBCSP, we propose to examine the distribution of occupation/industry types between those with and without breast cancer. We will use unconditional logistic regression to estimate associations between occupation/industry type and breast cancer adjusting for known and suspected confounders. Based on our results and the current literature, we will use existing job exposure matrices to explore the role of occupational exposures on the pathway between work and the risk of developing breast cancer.

This study is significant in its use of the LIBCSP data, a rich dataset of environmental exposures that has not been previously explored from an occupational lens. This dataset is also ideal given its inclusion of many of the known and suspected risk factors for breast cancer, which can then be controlled for in the analyses. It will add to the scant literature on occupational exposures among an all-female cohort and occupational breast cancer risk in the United States.

To perform this study, we have assembled a strong study team with expertise in breast cancer epidemiology, occupational medicine, occupational epidemiology, and cancer research. We will also capitalize on the wealth of statistical knowledge available through the Biostatistics and Bioinformatics Facility Core and utilize them to for data management and statistical analyses. We believe this study team can complete the current goals and position themselves for ongoing research collaborations.

Nearly eight million people in Latin America are infected with Trypanosoma cruzi the etiologic agent of Chagas disease. While treatable if diagnosed early, most acute cases are asymptomatic and go undiagnosed. When left untreated, T. cruzi enters a chronic phase of infection, evades the immune system and becomes a chronic cardiac, gastrointestinal, and/or neurologic Chagas disease. Chagas disease results in nearly 12,000 deaths annually, which is ten times the number of deaths caused by Malaria in this region, making it the leading cause of parasitic death in the Americas. Yet despite this figure, Chagas is still classified as a Neglected Tropical Disease (NTD) by the WHO and receives less then 1% of all funding for NTDs. However, early detection and treatment are paramount to reducing morbidity and mortality of Chagas disease.

This study aims to identify the effect of environmental exposures on congenital Chagas transmission and negative birth outcomes in Santa Cruz, Bolivia, where 20% of women are seropositive for T. cruzi. We will leverage an existing congenital Chagas cohort with over 7,000 mother-child dyads and freely available girded remote sensing environmental data to evaluate environmental risk factors for adverse birth outcomes and congenital Chagas transmission. We will develop pregnancy specific environmental exposure profiles by incorporating the air pollution, temperature, humidity, and study questionnaire derived socioeconomic status, and maternal T. cruzi positivity for Santa Cruz, Bolivia. We will use these profiles to evaluate the association between the environment and adverse birth outcomes and the rate of congenital T. cruzi transmission. Furthermore, we will assess the association of socioeconomic measures with risk of adverse birth outcomes and the rate of congenital T. cruzi transmission. To our knowledge this is the first study to investigate the effects of environmental exposures on congenital Chagas transmission. Lastly, this pilot-study to provide substantial support for a K99/R00 application.