GENETIC & EPIGENETIC MODIFIERS OF MATERNAL-FETAL TRANSFER OF TOXICANTS & OUTCOMES -
DESCRIPTION (provided by applicant)
The purpose of this Mentored Research Scientist Development Award is to support the interdisciplinary career development of the candidate, Dr. Adrienne Ettinger, who is trained as an environmental epidemiologist. This award will support the candidate for a period of mentored research and additional training in scientific and laboratory methods relevant to genetic and molecular epidemiology. This will enable her to subsequently develop an independent, interdisciplinary research program with a focus on transgenerational effects of environmental exposures, including the identification of molecular markers for noncancer (reproductive) health outcomes and analysis of complex gene-environment-nutrient interactions. The proposal outlines a Career Development Plan which includes working with established experts in genetic and molecular biology, endocrinology, toxicology, and advanced statistics, and is enhanced not only by the intellectual and laboratory resources described herein, but also by carefully chosen training activities and a career development involving laboratory experience, didactic instruction, seminars, and both formal and informal exchanges with mentors. The research component is aimed at evaluating if specific genes (VDR, CaSR, PTHR1), involved in the regulation of calcium homeostasis, modify the relationships between maternal lead biomarkers and physiologic parameters during pregnancy and, ultimately, influence fetal and early infant exposures and birth outcomes. An exploratory aim will investigate genomic imprinting and gene expression in the maternal-fetal unit using evolutionary theories of "gestational conflict" to develop a conceptual framework for understanding these complex interactions at the molecular level. The proposed research takes advantage of archived data and biologic specimens from three sequentially-enrolled longitudinal birth cohorts, and a newly-funded forth birth cohort, which provides a unique opportunity to address the scientific aims and makes efficient use of existing resources from an established, ongoing, and productive collaboration between researchers in the U.S. and Mexico and addresses research areas pertinent to the NIEHS areas of special interest: "Single Nucleotide Polymorphisms and Disease Susceptibility" and "Epigenetics: Role in Environmentally Induced Diseases/Dysfunction."
Relevance: Epidemiologic and experimental evidence suggest that environmental agents are reproductive toxicants, but relatively little is known about the biological mechanisms of effect. The objective of this work is to understand how common genetic variants, involved in calcium regulation, may impact toxicant-induced pregnancy and developmental outcomes.
