Cycle 4 - October 2021 OEFC Research Voucher Awards
Medium OEFC Research Voucher Award(s):Medium research voucher applications support the expenses (up to $5,000) associated with critical exploratory research and proof-of-concept studies needed by CIEHS members for hypothesis generation and grant (re)submission.
1. Principal Investigator: Barbara J. Clark, Ph.D.
Collaborator: Carolyn M. Klinge, Ph.D.
Title: STARD5 and lipid dysregulation with ER stress
Description: Environmental exposure to persistent pollutants is recognized as a risk factor for development of metabolic diseases. The risk is greater when combined with underlying genetic and dietary factors. Chronic endoplasmic reticulum (ER) stress from over nutrition and environmental toxicants can lead to inflammatory responses that promote development of toxicant-associated steatohepatitis (TASH), yet the mechanisms that promote disease progression are complex and not well defined. Using a novel Stard5 knock-out mouse model this project will test whether the loss of STARD5 is risk factor for development of steatohepatitis under ER stress conditions. STARD5 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid-transfer (START) domain family of lipid transport proteins, and is highly expressed in key cell types that promote steatohepatitis. We have identified changes in select target genes that support Stard5-/- mice are more sensitive to tunicamycin-induced changes in liver lipid metabolism. The work proposed will define the liver transcriptome for wild type vs Stard5-/- mice after tunicamycin-induced ER stress. Using this unbiased approach our understanding of the impact of Stard5 knockout on mouse liver mRNA transcriptomes under normal and stress conditions will be expanded. The novelty is there are no transcriptomics reports using the Stard5-/- mice. The work will provide proof-of-concept support to expand investigations on loss of STARD5 in contributing to diet-environmental pollutant-induced TASH.
2. Principal Investigator: Anna Gumpert, Ph.D.
Collaborator: Daniel Conklin, Ph.D.
Title: Combined Effects of Air Pollution and Hypertension on Cardiovascular Remodeling
Description: Human population studies indicate that 60-70% of the premature deaths attributed to air pollution are cardiovascular deaths. High blood pressure and cardiac fibrosis are important contributors to detrimental structural and functional changes and progressive worsening of heart disease. Our studies aim to investigate how environmental factors (i.e. air pollution) contribute to worsening outcomes and decreased quality of life.