Ralph C. Budd, M.D.

Title
Professor of Medicine
Department
Department of Medicine
Institution
University of Vermont
Address
89 Beaumont Avenue
Given Medical Building D-305
City, State, Zip
Burlington, VT 05405-0068
Phone
(802) 656-2286
E-mail
ralph.budd[at]uvm.edu
Website
http://www.uvm.edu/medicine/vciid/
Research Field
Immunology
Award Year
1990

Research

My laboratory is examining the signal pathways of Fas and its inhibitor, cFLIP, in murine models of autoimmunity and in human Lyme arthritis. The Fas-deficient lymphoproliferative (lpr) mouse pictured above develops an autoimmune disease resembling human lupus, as well as profound enlargement of lymph nodes. We are studying the types of lymphocytes that accumulate in the absence of Fas-induced death. In parallel studies, we are examining the alterations in Fas signaling caused by its natural inhibitor, cFLIP. Ligation of Fas recruits the adaptor protein FADD, which then recruits the protease caspase-8. cFLIP is homologous to caspase-8 but lacks protease activity and hence is a competitive negative regulator of Fas-induced death. We have observed that cFLIP also connects to the MAP kinase ERK, and NF-kB pathways and can thus divert Fas death signals toward signal pathways associated with cell growth. We are examining this using overexpression of wild type and mutant forms of cFLIP in cell lines and transgenic mice.