The goal of this project is to understand the role Nrf1 in cellular stress response pathway. We hypothesize that depending on the type of stimuli, different Nrf1 isoforms regulate different adaptive responses (oxidative, ER, proteotoxic) to cellular stress. We will first determine stress-activated genes that are controlled by Nrf1 and its isoforms. Next, we will use genome-wide approaches that will permit comprehensive, and quantitative analyses to investigate redundancy and specificity between Nrf1 and Nrf2 in mediating cellular stress responses. Third, we will delineate mechanisms by which Nrf1 is regulated. Our findings should have broad and significant impact on our understanding of cellular stress response pathways.

Public Health Relevance

Research to delineate the signaling and response pathways elicited by reactive oxygen species and environmental toxicants is important for the understanding of pathogenesis, and prevention of various diseases. This proposal focuses on investigating the role of Nrf1 transcription factor in cellular stress response. We will determine genes controlled by Nrf1 and its isoforms, and mechanism by which their functions are controlled. These studies should provide a better understanding of the role of Nrf1 in stress response that is relevant to the pathophysiology and therapy of stress-related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES029481-01A1
Application #
9737144
Study Section
Xenobiotic and Nutrient Disposition and Action Study Section (XNDA)
Program Officer
Shaughnessy, Daniel
Project Start
2019-08-01
Project End
2024-04-30
Budget Start
2019-08-01
Budget End
2020-04-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Pathology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617