Diversity Supplement for Mechanisms of Phthalate Toxicity in the Ovary

项目摘要/摘要 这是一项关于多样性补充的建议，以资助一个 新泽西理工学院环境科学博士项目的优秀博士生。 这项提议的父母赠款是R00ES031150-30，以促进热那亚·华纳博士过渡到 化学与环境系助理教授的独立研究生涯 她在新泽西理工学院学习理科，在那里她拥有不同的科学背景 化学和生物学，研究环境健康中的重要研究问题。华纳博士已经 在内分泌干扰和可持续化学方面进行了广泛的培训，并在 伊利诺伊大学的生殖毒理学，在乔迪·A·弗劳斯博士的指导下，她在那里 学会了成为一名成功的独立调查员所需的技术和专业技能 生殖毒理学领域的领先者。在她的新实验室里，华纳博士通过 邻苯二甲酸酯，一组无处不在的人类接触的内分泌干扰化学物质，会导致卵巢 毒性。此外，她还研究了邻苯二甲酸酯在卵巢组织中的代谢，因为邻苯二甲酸酯的代谢物 调节邻苯二甲酸盐诱导的毒性效应，导致不孕不育和卵巢早衰。在散文中 在研究方面，华纳博士将指导多样性补充候选人考特尼·波茨在 最初项目的范围旨在打造他自己的研究利基市场。父项目目标的具体目标1 通过质谱学和成像方法确定培养过程中邻苯二甲酸盐如何分配到卵巢组织 使用化学修饰的邻苯二甲酸酯。特定目标2将确定邻苯二甲酸盐毒性在不同细胞之间的差异 使用下一代测序技术确定卵巢的类型。最后，特殊目标3将确定基因组 应用配对化学亲和捕获生化技术对邻苯二甲酸盐在卵巢中的定位 使用大规模并行DNA测序(Chem-seq)来提供目标基因和蛋白质的信息 邻苯二甲酸盐。总体而言，拟议的研究将提供新的化学和机械洞察的原因 邻苯二甲酸盐在卵巢中引起的毒性，导致女性不孕和卵巢早衰。这个 方法将化学和生物技术相结合，开发出一种新的、广泛适用的技术 研究内分泌干扰物的作用机制。

PROJECT SUMMARY/ABSTRACT This is a proposal for a Diversity Supplement to fund hands-on research training and career development for a talented doctoral student in the Environmental Science PhD program at the New Jersey Institute of Technology. The parent grant for this proposal is R00ES031150-30 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, Courtney Potts, in pursuing research within the scope of the original project aims to craft his 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.