【報告題目】Discovery and Therapeutic Development of Extracellular Heat Shock Protein-90alpha (Hsp90α) for Wound Healing and in Cancer Drugs

【報告人】栗衛博士

【邀請人】夏偉梁博士

【時間】11月25日（周三）16：00-17：00

【地點】Med-X 108 （閔行文選樓323會議室同步視頻）

【摘要】Extracellular Hsp90 proteins, including "membrane-bound", "released" and "secreted", were first reported more than two decades ago. Only studies of the past 10 years have begun to reveal a picture for when, how and why Hsp90 gets exported by normal and tumor cells. Normal cells secrete Hsp90 in response to tissue injury. Tumor cells have managed to constitutively secrete Hsp90 for tissue invasion. In either case, sufficient supply of the extracellular Hsp90 can be guaranteed by its unusually abundant storage inside the cells. A well-characterized function of secreted Hsp90α is to promote cell motility, a crucial event for both wound healing and cancer. The reported targets for extracellular Hsp90α include MMP2, LRP-1, tyrosine kinase receptors and possibly more. The pro-motility activity of secreted Hsp90α resides within a fragment, called 'F-5', at the boundary between linker region and middle domain. Inhibition of its secretion, neutralization of its extracellular action or interruption of its signaling through LRP-1 block wound healing and tumor invasion in vitro and in vivo. In normal tissue, topical application of F-5 promotes acute and diabetic wound healing far more effectively than US FDA-approved conventional growth factor therapy in mice. In cancer, drugs that selectively target the F-5 region of secreted Hsp90 by cancer cells may be more effective and less toxic than those that target the ATPase of the intracellular Hsp90.

【報告人簡介】After receiving his college education from the Xinjiang University (Urumqi), Li Wei went to the US in 1984. He received MS degree in 1988 and PhD degree in 1991 under supervision of Dr. E Richard Stanley from the Albert Einstein College of Medicine, Bronx, New York. Following a 18-month post-doctoral/instructor fellowship with Dr. Joseph Schlessinger (Professor and Chairman, the Department of Pharmacology at New York University Medical Center), he joined the faculty of the Ben May Institute for Cancer Research at the University of Chicago in the fall of 1993 as an Assistant Professor on tenure track. He was recruited to University of Southern California (USC) Keck School of Medicine in 1999. He rose to full professor in 2006. He is currently a Professor and Director of the GMCB Graduate Program at USC Keck School of Medicine. His research interest focuses wound healing and cancer progression. His lab is the first to identify the important role for the SECRETED form of heat shock protein-90 (Hsp90) in skin wound healing, as well as in tumor cell motility, invasion and metastasis. He holds four patents on secreted Hsp90 as a drug candidate to treat chronic wounds and triple negative breast cancer and all the patents have entered their industrial development phases. His research program is currently supported by two NIH grants (RO1) and one VA research grant (with Dr. David Woodley, MD). He is the principle or co- author of more than 74 peer-reviews publications in biomedical journals, including Cell, Nature, Science, PNAS, Nature Medicine, Journal of Clinical Investigation (JCI), EMBO J,Molecular Cell Biology (MCB), Molecular Biology of Cell (MBC), Journal of Cell Biology (JCB), JCS and JBC. He is a frequent speaker at national and international levels. His recent representative publications are: Cheng et al, (2011) J Clinic. Invest. 121:4348-4361; Sahu et al. (2012) Mol. Biol. Cell. 23:602-613; Tsen et al. (2013)Mol Cell Biol., 33:4947-4953 and Zou et al. (2015) EMBO J under revision.