Biochemistry - School of Medicine
Research at a glance
Area(s) of Expertise
BTB-Kelch substrate adaptor family in development, oncogenesis and neurodegeneration.
Our laboratory has identified an E3 ubiquitin ligase complex that is regulated by oxidative stress. The major substrate of this ubiquitin ligase complex is the Nrf2 transcription factor, which is brought into the ubiquitin ligase complex by the Keap1 protein. Keap1 contains redox-sensitive cysteine residues that, when modified by reactive electrophilic compounds, including reactive oxygen species (ROS), alter the ability of Keap1 to target Nrf2 for ubiquitin-dependent degradation. This leads to increased stabilization of Nrf2 and to activation of a transcriptional program that enables cells to neutralize reactive molecules and maintain cellular redox homeostasis. We have identified several new partners for Keap1, including a protein termed PGAM5 that anchors the Keap1-Nrf2 complex to the outer mitochondrial membrane. PGAM5 also regulates the morphological appearance of mitochondria. We propose that PGAM5 is a critical link between generation of ROS by mitochondria and Nrf2-dependent anti-oxidant genes. We are currently characterizing a gene knockout mouse model for PGAM5.
- Ph.D. Biochemistry, University of California-San Diego
- M.S. Organic Chemistry, University of Washington
- B.S. Chemistry, Calvin College