The goal of my K99/R00 career development plan is to launch an independent research program in reproductive and environmental epidemiology of endocrine-disrupting chemicals (EDCs) which includes evaluating social determinants of health that may affect overlapping biologic pathways. To accomplish this goal, I will enhance my expertise in environmental health sciences with didactic and hands-on training in reproductive biology, social epidemiology/stress science, and environmental epidemiologic methods. This specialized training will allow me to achieve my long term goal of becoming an independent academic investigator and offering new insights on the cumulative impacts of environmental and social factors on reproductive health. The primary goal of my research plan is to evaluate the independent effects of polybrominated diphenyl ethers (PBDEs) and psychosocial stress on thyroid hormone disruption and consequent perinatal outcomes among a population of socioeconomically and racially diverse pregnant women. This work is particularly innovative as both PBDEs and psychosocial stress can impact the thyroid system, suggesting a biologic plausibility for interaction, however the two exposures have never been examined simultaneously in a human study. During the K99 mentored phase, under the primary mentorship of Dr. Tracey Woodruff, I will use innovative measures to characterize biologically-relevant exposures to PBDEs and psychosocial stress and their effects on thyroid hormone disruption. Exposure to PBDEs will be assessed using both PBDE congeners as well as their hydroxylated metabolites (OH-PBDEs). Psychosocial stress will be evaluated with subjective measures of stress and telomere length, a biomarker of cellular aging that is influenced by psychosocial stress. In the independent phase, I will apply this knowledge to investigate the independent effects of PBDEs and psychosocial stress on adverse perinatal outcomes, such as gestational hypertension, preterm birth, and low birth weight, and assess whether these effects are mediated via the thyroid system. The integration of this work will enable me to develop the necessary methodological and biological frameworks to examine the combined, and potentially synergistic, effects of environmental and psychosocial factors on perinatal outcomes in future R01 studies. I am well positioned to accomplish these goals at the University of California, San Francisco, a highly respected research institution, with a strong environmental reproductive health program, a world-renowned faculty with expertise in psychosocial stress, and an extensive biomedical infrastructure. My primary mentor and co-mentors in reproductive sciences, environmental epidemiology, health disparities, stress science, and biostatistics will guide the process whereby I learn the methods that are required to accomplish the goals set forth in this proposal. This project represents the cutting-edge of health disparities and environmental health research and seeks to answer critical scientific as well as policy-relevant questions for improving the health of vulnerable populations who often face disproportionate and elevated exposures to multiple chemical and non-chemical stressors.

Public Health Relevance

The goal of this project is to prepare Dr. Ami Zota to transition to a position as an independent academic investigator in environmental health sciences focusing on the consequence of endocrine-disrupting chemicals (EDCs) during pregnancy and social factors that may affect overlapping biologic pathways. She will conduct epidemiologic analyses to investigate the effects of polybrominated diphenyl ether (PBDE) flame retardants and psychosocial stress on perinatal outcomes and assess whether these effects are mediated by the thyroid system. Results from this work will improve pregnancy outcomes and inform public health policy, particularly for vulnerable subpopulations, who often encounter elevated exposures to chemical and non-chemical stressors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Transition Award (R00)
Project #
5R00ES019881-04
Application #
8741963
Study Section
No Study Section (in-house review) (NSS)
Program Officer
Gray, Kimberly A
Project Start
2013-09-25
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
George Washington University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20052
Varshavsky, Julia R; Morello-Frosch, Rachel; Woodruff, Tracey J et al. (2018) Dietary sources of cumulative phthalates exposure among the U.S. general population in NHANES 2005-2014. Environ Int 115:417-429
Zota, Ami R; Geller, Ruth J; Romano, Laura E et al. (2018) Association between persistent endocrine-disrupting chemicals (PBDEs, OH-PBDEs, PCBs, and PFASs) and biomarkers of inflammation and cellular aging during pregnancy and postpartum. Environ Int 115:9-20
Geller, Ruth J; Brotman, Rebecca M; O'Brien, Katie M et al. (2018) Phthalate exposure and odds of bacterial vaginosis among U.S. reproductive-aged women, NHANES 2001-2004. Reprod Toxicol 82:1-9
Zota, Ami R; Mitro, Susanna D; Robinson, Joshua F et al. (2018) Polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDE metabolites (OH-PBDEs) in maternal and fetal tissues, and associations with fetal cytochrome P450 gene expression. Environ Int 112:269-278
Nomura, Sarah Jo; Robien, Kim; Zota, Ami R (2017) Serum Folate, Vitamin B-12, Vitamin A, ?-Tocopherol, ?-Tocopherol, and Carotenoids Do Not Modify Associations between Cadmium Exposure and Leukocyte Telomere Length in the General US Adult Population. J Nutr 147:538-548
Zota, Ami R; Singla, Veena; Adamkiewicz, Gary et al. (2017) Reducing chemical exposures at home: opportunities for action. J Epidemiol Community Health :
Zota, Ami R; Shamasunder, Bhavna (2017) The environmental injustice of beauty: framing chemical exposures from beauty products as a health disparities concern. Am J Obstet Gynecol 217:418.e1-418.e6
Varshavsky, Julia R; Zota, Ami R; Woodruff, Tracey J (2016) A Novel Method for Calculating Potency-Weighted Cumulative Phthalates Exposure with Implications for Identifying Racial/Ethnic Disparities among U.S. Reproductive-Aged Women in NHANES 2001-2012. Environ Sci Technol 50:10616-10624
Zota, Ami R; Riederer, Anne M; Ettinger, Adrienne S et al. (2016) Associations between metals in residential environmental media and exposure biomarkers over time in infants living near a mining-impacted site. J Expo Sci Environ Epidemiol 26:510-9
Mitro, Susanna D; Birnbaum, Linda S; Needham, Belinda L et al. (2016) Cross-sectional Associations between Exposure to Persistent Organic Pollutants and Leukocyte Telomere Length among U.S. Adults in NHANES, 2001-2002. Environ Health Perspect 124:651-8

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