研究领域

Biochemistry

Our research group focuses on understanding receptor-mediated biological processes involved in cancer development. Involvement of membrane receptors, such as G Protein-Coupled Receptors (GPCRs) in cancers has been extensively documented. Recent advances in the use of structural biology to characterize the behaviors of these receptors enable detailed characterization of receptor signaling as well as effective development of therapeutic agents. Orphan GPCRs are highly expressed in cancer cells. One of our research focus is on the deorphanization and characterization of orphan GPCRs. Our second focus is to use high-throughput screening approaches to identify compounds/antibodies that selectively stabilize receptors in specific conformations to facilitate crystallization and structure determination. The general approach to address these scientific questions is built upon the top-notch technology for membrane protein structural determination, Lipid Cubic Phase (LCP), which is directed toward the understanding of membrane protein (mainly GPCRs) molecular pharmacology, the conformational changes of membrane proteins following ligand binding, and specifically, the phenomenon of biased ligand signaling where compounds with subtly different chemical structures may induce differential downstream signaling and distinct pharmacological effects.

近期论文

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"Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography," W. Liu, A. Ishchenko and V. Cherezov, Nat Protoc 9 2123-2134 (2014) "Serial femtosecond crystallography of G protein-coupled receptors," W. Liu, D. Wacker, C. Gati, G.W. Han, D. James, D. Wang, G. Nelson, U. Weierstall, V. Katritch, A. Barty, N.A. Zatsepin, D. Li, M. Messerschmidt, S. Boutet, G.J. Williams, J.E. Koglin, M.M. Seibert, C. Wang, S.T.A. Shah, S. Basu, R. Fromme, C. Kupitz, K.N. Rendek, I. Grotjohann, P. Fromme, R.A. Kirian, K.R. Beyerlein, T.A. White, H.N. Chapman, M. Caffrey, J.C.H. Spence, R.C. Stevens and V. Cherezov, Science 342 1521-1524 (2013) "Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions," W. Liu, E. Chun, A.A. Thompson, P. Chubukov, F. Xu, V. Katritch, G.W. Han, C.B. Roth, L.H. Heitman, A.P. IJzerman, V. Cherezov, and R.C. Stevens, Science 337 232-236 (2012) "Structure of the Nociceptin/Orphanin FQ Receptor," A.A. Thompson*, W. Liu*, E. Chun*, V. Katritch, H. Wu, E. Vardy, X-P Huang, C. Trapella, R. Guerrini, G. Calo, B.L. Roth, V. Cherezov, and R.C. Stevens, Nature 485 395-399 (2012)