Endocrine-Disrupting Chemical (EDC) Mixtures in Relation to Metabolic Syndrome (MetS) and Metabolomic Mechanisms in a Prospective Cohort of Hispanic Women - I am an environmental epidemiologist with a main research focus on the “exposome” and its role in obesity-related outcomes and chronic disease. The training presented in this proposal will enable me to become an independent public health researcher in the field of environmental epidemiology, specializing in endocrine-disrupting chemical (EDC) mixtures and long-term cardiometabolic health in women. This project addresses the role of EDCs in the onset of metabolic syndrome (MetS), which is a cluster of conditions that can increase the risk for heart disease and type 2 diabetes, as well as examines potential underlying mechanisms. This opportunity will allow me to hone the skills needed to become an independent investigator by 1) expanding my knowledge in exposure-mixture methods, 2) acquiring the tools to analyze and interpret high-dimensional metabolomics data, and 3) advancing my expertise in a relatively highly prevalent, yet understudied, metabolic condition. The rising MetS epidemic has reached alarming rates in North America, with a prevalence in adults of more than one-third in the US. Currently, the etiology of MetS and its mechanisms of action are poorly understood. An emerging risk factor for MetS is exposure to environmental “obesogens”, such as EDCs. Endocrine disruptors can act in the body by mimicking steroid hormones and increasing oxidative stress, thereby triggering MetS components such as hypertension, abdominal adiposity, hyperglycemia, or dyslipidemia. Moreover, pregnancy is likely a susceptible period that could exacerbate the deleterious effects of EDCs with long-lasting consequences for women’s health. I will leverage ~400 pregnant women from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) prospective cohort to examine 1) the longitudinal association between EDC exposure-mixtures—phthalates, metals, air pollutants, pesticides, and PFAS—and MetS onset, 2) the subsequent alteration in individual metabolites and pathways stemming from these exposures, and 3) the mediating metabolomic features characteristic of MetS. The training originating from the K99 phase of this proposal will ensure the correct implementation of chemical mixtures-MetS association analyses in the first phase of the award (K99), and of mixture- omics and mediation analyses during the second phase (R00). A renowned multi- disciplinary team of experts will be convened to help me achieve my goals, with whom I will meet and discuss rigorous training related to environmental endocrinology and metabolism (Dr. Damaskini Valvi), interpretation in longitudinal cohort data (Dr. Martha Téllez-Rojo), maternal health (Dr. Lida Chatzi), metabolomics (Dr. Dinesh Barupal), and statistical methodology for exposure-mixtures and mediation analysis (Dr. Elena Colicino). Formal coursework, scholarly seminars, guided readings, conferences, and workshops will also be incorporated into my curriculum, collectively helping me build my career as an independent environmental epidemiologist with a focus on cardiometabolic diseases.
