Diversity Supplement for Updating the Mixture in Mechanisms of Phthalate Toxicity in the Ovary

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PROJECT SUMMARY/ABSTRACT This is a proposal for a Diversity Supplement to fund hands-on research training and career development for a promising research technician receiving post-baccalaureate training at the New Jersey Institute of Technology. The parent grant for this proposal is R00ES031150 to facilitate Dr. Genoa Warner’s transition to an independent research career as an Assistant Professor in the Department of Chemistry and Environmental Science at the New Jersey Institute of Technology, where she draws from her diverse scientific background in chemistry and biology to investigate important research questions in environmental health. Dr. Warner has extensive training in endocrine disruption and sustainable chemistry and has completed postdoctoral training in reproductive toxicology at the University of Illinois under the mentorship of Dr. Jodi A. Flaws, where she has learned technical and profession skills necessary for her to become a successful independent investigator and leader in the field of reproductive toxicology. In her new laboratory, Dr. Warner investigates the mechanisms by which phthalates, a group of endocrine disrupting chemicals with ubiquitous human exposure, cause ovarian toxicity. Further, she investigates the metabolism of phthalates by ovarian tissue because phthalate metabolites mediate phthalate- inducted toxic effects, contributing to infertility and premature ovarian failure. In the prosed studies, Dr. Warner will mentor the Diversity Supplement candidate, Stephanie Martinez, in pursuing research within the scope of the original project aims to craft her own research niche. Specific Aim 1 of the parent project aims to identify how phthalates partition into ovarian tissue during culture via mass spectrometry and imaging methods using chemically modified phthalates. Specific Aim 2 will determine how phthalate toxicity varies between cell types of the ovary using next generation sequencing techniques. Finally, Specific Aim 3 will identify the genomic localization of phthalates in the ovary by adapting the biochemical technique of chemical affinity capture paired with massively parallel DNA sequencing (Chem-seq) to provide information on the genes and proteins targeted by phthalates. Overall, the proposed studies will provide novel chemical and mechanistic insight into causes of phthalate-induced toxicity in the ovary that contribute to female infertility and premature ovarian failure. The methods combine chemical and biological techniques to develop a new, widely applicable technology for investigating the mechanisms of endocrine disrupting chemicals.