My lab is developing inhibitors of the human 60 kilodalton heat shock protein (HSP60) chaperonin system as a mechanistically unique anti-cancer strategy. HSP60 is a remarkable example of a diverse class of specialized proteins, called molecular chaperones, which help other proteins fold to their native states. We believe HSP60 is a promising chemotherapeutic target because in many cancers (e.g. colon, lung, breast, cervical, ovarian, and prostate), the abnormally propagating cells have hijacked HSP60 regulation to help promote cancer progression. An increasing array of biological processes are being associated with HSP60/10 function, including apoptotic, pro-survival, and metastatic pathways. The role of HSP60/10 in oncogenesis is not clear and may result from cells accumulating HSP60 in the cytosol either with or without mitochondrial release, the latter of which would be naive, still bearing its N-terminal mitochondrial import sequence. We are developing inhibitors against both naive and mitochondrial HSP60 to elucidate possible biochemical differences and to help understand the role of each in pathogenesis. As HSP60 is structurally and functionally distinct from the HSP90 and HSP70 chaperones, it represents a mechanistically unique target for pharmacologic exploitation with the potential to synergize with other chemotherapeutic strategies (in particular with HSP90, HSP70, and proteasome inhibitors).
Post-doctoral Fellowship - University of Washington, WA 2010-2012
Post-doctoral Fellowship - Yale School of Medicine, New Haven, CT 2008-2010
Post-doctoral Fellowship - The Scripps Research Institute, La Jolla, CA 2006-2008
Ph.D. - The Scripps Research Institute, La Jolla, CA 2001-2006
