S423 SLU (850 Republican St.)
Our research focuses on receptor signal transduction in the brain, in embryonic development and in neurodegenerative diseases. Presently our attention is directed to two projects. One project addresses the hypothesis that the capacity of the neurotrophin receptor p75 to signal is gated by reactive oxygen species. Oxidative stress controls formation of a disulfide bond linking subunits of a dimeric p75 complex that is required for neurotrophin-dependent activation of the receptor. The second project generates motor neurons and cortical neurons from induced pluripotent stem cell lines derived from individuals with genetically determined neurodegenerartive diseases. A primary focus of the second project tests the hypothesis that the many genes mutated in Charcot-Marie-Tooth type 2 (CMT2) disturb fission/fusion dynamics and transport of mitochondria in axons of motor neuron axons. We hypothesize that axonal degeneration in CMT2 results from inappropriate reactivation of a signaling program that normally controls motor axon pruning during development. This signaling program is postulated to employ a mitochondria-dependent BAX/caspase signaling pathway.
Copyright © 2003-2014 Molecular & Cellular Biology Program, University of Washington
Fred Hutch | University of Washington
Institute for Systems Biology (ISB)| Center for Infectious Disease Research