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发布人:马文君  发布时间:2017-04-26   浏览次数:14

生命学院邀,加州大学河滨分校的Dr. Xin Ge将于510访问生命学院并在哈工大生命学院做学术报告,具体安排如下,迎感趣的教和同学参加


报告题目Novel methods for protease inhibitory mAbs with high selectivity and high potency

告 Dr. Xin Ge

Assistant Professor, Department of Chemical and Environmental Engineering at University of California, Riverside.

报告时间2017510日下午2:00

地    :科学园2E411

  

报告简介:

As extremely important signaling molecules, proteases precisely control a wide variety of physiological processes, and thus represent one of the largest families of potential pharmaceutical targets. Considering ~2% of human genome is estimated to encode proteases, specificity is desired for any protease inhibition therapy. However, the proteolytic mechanisms are highly conserved among the same class or family of proteases, thus distinguishing proteases using small molecule inhibitors is exceedingly difficult (e.g. fails of board spectrum MMP inhibitors in clinical trials). On the other hand, topologies of antibody binding sites are not suitable for concave protease catalytic clefts, and lack of function-based rather than binding-based selection methods makes generation of inhibitory antibodies a daunting challenge. By construction of synthetic antibody libraries enriched with convex conformation, and development of functional screening methods based on epitope-specific FACS, genetic selection, and deep sequencing, we isolated a panel of highly potent and selective Fab inhibitors targeting all four main classes of proteases: matrix metalloproteinases (MMP-14, a predominant target in cancer metastasis; MMP-9, in neuropathic pains), beta-secretase 1 (BACE1, an aspartic protease in Alzheimer), cathepsin K (a cysteine protease in cancer), and Alp2 (a serine protease in aspergillosis). Particularly, Fab 3A2 inhibited MMP-14 on its physiological substrates with an inhibition potency of 9.7 nM. Enzyme inhibition kinetics, competitive ELISA and epitope mapping studies collectively suggested that Fab 3A2 was a competitive inhibitor binding to the vicinity of MMP-14 reaction cleft. In mouse models, mAb 3A2 significantly reduced tumor cell spreading. These novel methods allow us to discover inhibitory mAb with exclusive selectivity for a broad range of biomedically important proteases but challenging for conventional antibody techniques.

  

报告人简介:

Dr. Xin Ge is an Assistant Professor in the Department of Chemical and Environmental Engineering at University of California, Riverside. He received his B.S. in Chemical Engineering (2000) and M.S. in Biochemical Engineering (2003) from Tsinghua University and Ph.D. from McMaster University, Canada (2008). Prior to joining the faculty of UCR in 2011, Dr. Ge was a postdoc fellow / research associate at the Department of Chemical Engineering, University of Texas, Austin. Dr. Ge’s research interest is in the area of protein engineering, mainly focusing on therapeutic antibody / enzyme discovery and engineering. He was a NSERC post-doctoral fellow and an awardee of National Science Foundation (NSF) Faculty Early Career Development Program. His research is currently supported by NSF CAREER, NIH R01, USDA, and California breast cancer research program.