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 expression and function is regulated. Our findings should have broad and significant impact on our understanding of cellular stress response pathways.
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 stress- related diseases. This proposal focuses on investigating the role of Nrf1 transcription factor in stress response in cells. We will determine stress response 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.
