Systems approach to define AHR ligand toxicity on reproductive system development

Oregon State University, Corvallis OR

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by candidate): My long-term career goal is to become an independent researcher and obtain an academic faculty position at a top-tier academic research university, where I may teach and mentor students in the fields of environmental and molecular toxicology. My primary research interests focus on determining chemical origins for human health problems, particularly how environmentally relevant endocrine disrupting chemicals perturb vertebrate development. Thus far my background training has been primarily in environmental health sciences and toxicology, with additional training in biochemistry and molecular biology. With this grant application, I will adhere to a rigorous mentored training curriculum to acquire expertise in emergent techniques, including next- generation RNA sequencing, genomics, and computation biology. Using these techniques and new molecular methods, systems biology and bioinformatics will be a cornerstone of my independent research career. Environment: The research and career development plans described in the grant application will be carried out at Oregon State University (OSU). There, I will engage with highly successful faculty and research staff, and take advantage of unique state-of-the-art facilities and outstanding institutional training environment. OSU has a rich training environment, and is therefore an ideal location to achieve my career goals. My selected mentors are top scientists in the fields of developmental and systems toxicology and computational biology, which will provide me with the best possible training and opportunities to succeed as an independent scientist. My primary mentor, Dr. Robert Tanguay is widely recognized toxicologist that has championed zebrafish as a relevant and modern model for systems toxicology and human health related diseases. Dr. Tanguay has strong collaborative relations with my co-mentors, Dr. Susan Tilton and Dr. Katrina Waters, both of whom are highly regarded computational biologists. This unique opportunity will afford me with training in one of the best aquatic laboratories in the world and top-notch computational biology facilities at the OSU-CGRB/PNNL. Research: The goal of this research project is to determine how endocrine disrupting chemicals adversely affect development of the reproductive system. Concerns regarding human exposures to historical and emerging AHR environmental ligands are compounded by evidence that AHR activity modulates endocrine pathways. Specifically, a systems biology approach will be used to study how aryl hydrocarbon receptor (AHR) ligands perturb neuroendocrine- and sex-steroid pathways early in development, leading to reproductive health effects later in life. Zebrafish are an ideal developmental vertebrate model for use with cutting edge deep sequencing technologies to dissect molecular events that lead to reproductive toxicity, particularly the involvement of non-coding regulatory RNAs in modulating the ER signaling. These studies will not only enhance our understanding of model AHR ligands, but also for a variety of ligands which lack toxicity data.