Didier Picard

Institute:Department of Cell Biology, University of Geneva, Switzerland
Title:The Hsp90 molecular chaperone: of partners, places, drugs and cancer
Abstract:["Cellular matchmakers such as the molecular chaperone heat-shock protein 90 (Hsp90) and its partner proteins are required for a multitude of cellular processes and for the maintenance of cellular protein homeostasis. The ATP-dependent Hsp90 machine assists a subset of proteins during posttranslational folding and macromolecular assembly, and in some cases it even plays a regulatory role. In eukaryotes, this molecular machine is essential for viability. Cancer cells and a large proportion of cancer driver genes are particularly Hsp90-dependent and sensitive to Hsp90 inhibitors. Although this differential sensitivity is still poorly understood, it has led to major efforts to develop Hsp90 inhibitors for anti-cancer therapy. We are particularly interested in determining (i) the in vivo functions of the Hsp90 molecular chaperone complex both in mammalian cells and in the mouse, using genetic, biochemical, proteomic and pharmacological tools; (ii) the specific functions of key components such as the two core components Hsp90\u03b1 and Hsp90\u03b2, and the cochaperones p23, Aarsd1, Stip1 (Hop), Aha1 and Aha2; (iii) the key functions of Hsp90 as a network hub in the human proteome; (iv) the mechanisms responsible for the differential sensitivity to Hsp90 inhibitors of cancer cells versus normal cells; (v) the functions of the mitochondrial Hsp90 isoform Trap1 in the mouse and in cells."]
Host:Stefan RĂ¼diger