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

用于更新卵巢邻苯二甲酸盐毒性机制混合物的多样性补充

• 批准号: 10818882
• 负责人: Genoa R Warner
• 金额: $ 7.42万
• 依托单位: NEW JERSEY INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-05 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10818882
• 关键词: Acceleration; Affinity; Applications Grants; Behavior; Biochemical; Biological; Biology; Cell Culture Techniques; Cell membrane; Cells; Cessation of life; Chemical Structure; Chemicals; Chemistry; Child; Complex; Culture Media; DNA-Binding Proteins; Data; Development; Dioxins; Disease; Endocrine Disruptors; Endocrine disruption; Environment; Environmental Health; Environmental Science; Enzymes; Equipment; Esters; Exposure to; Family; Female; Female infertility; Funding; Gene Expression; General Population; Genes; Genetic Transcription; Genomics; Hormones; Human; Hydrocarbons; Illinois; Image; In Vitro; Industrialization; Infertility; Label; Laboratories; Learning; Length; Mass Spectrum Analysis; Massive Parallel Sequencing; Mediating; Medical; Mentors; Mentorship; Metabolism; Methods; Modernization; Molecular; Nature; New Jersey; Oocytes; Ovarian; Ovarian Follicle; Ovarian Tissue; Ovarian aging; Ovary; Phthalic Acids; Plasticizers; Population; Postbaccalaureate; Premature Ovarian Failure; Prevalence; Prevention; Property; Proteins; Public Health; Reproduction; Research; Research Personnel; Research Training; Sampling; Side; Solvents; Structure; Techniques; Technology; Testing; Tissues; Toxic effect; Toxicology; Toy; Training; Universities; Update; Urine; Visualization; Woman; building materials; career; career development; cell type; chromatin immunoprecipitation; consumer product; environmental chemical exposure; exposed human population; hands on research; imaging modality; innovation; insight; lipophilicity; men; mouse model; next generation sequencing; novel; ovotoxicity; parent grant; parent project; personal care products; phthalates; post-doctoral training; professor; receptor; reproductive; reproductive organ; reproductive system disorder; screening; skills; small molecule; toxicant; transcription factor

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.

项目总结/摘要 这是一项多样性补充提案，旨在资助实践研究培训和职业发展， 在新泽西理工学院接受学士后培训的有前途的研究技术人员。 该提案的母公司赠款为R 00 ES 031150，以促进热那亚华纳博士过渡到独立的 研究生涯作为助理教授在化学与环境科学系在 新泽西理工学院，在那里她利用她在化学和 生物学研究环境健康的重要研究问题。华纳博士受过广泛的训练 在内分泌干扰和可持续化学方面， 在Jodi A.博士的指导下，在伊利诺伊大学进行毒理学研究。缺陷，在那里她学会了技术 和专业技能，使她成为一个成功的独立调查员和领导者在该领域 生殖毒理学在她的新实验室里，华纳博士研究了邻苯二甲酸盐， 一组内分泌干扰化学品与人类普遍接触，导致卵巢毒性。她还 研究邻苯二甲酸酯通过卵巢组织的代谢，因为邻苯二甲酸酯代谢物介导邻苯二甲酸酯- 诱发毒性作用，导致不孕和卵巢早衰。在这些研究中，华纳博士 将指导多样性补充候选人，斯蒂芬妮马丁内斯，在追求范围内的研究， 最初的项目旨在打造她自己的研究利基。父项目的具体目标1旨在确定如何 在培养过程中，通过质谱和成像方法， 化学改性的邻苯二甲酸盐具体目标2将确定邻苯二甲酸酯毒性在细胞类型之间的变化， 利用下一代测序技术来检测卵巢。最后，具体目标3将确定基因组 应用化学亲和捕获配对的生物化学技术定位卵巢中的邻苯二甲酸酯 大规模并行DNA测序（Chem-seq），以提供靶基因和蛋白质的信息 邻苯二甲酸盐总的来说，拟议的研究将提供新的化学和机制的见解的原因， 邻苯二甲酸酯诱导的卵巢毒性，导致女性不孕和卵巢早衰。的 方法联合收割机结合化学和生物技术，开发一种新的、广泛适用的技术， 研究内分泌干扰物的作用机制。