Department of Pharmacology & Chemical Biology at the University of Pittsburgh
Cheng Zhang, PhD
Assistant Professor
E1358 Thomas E. Starzl Biomedical Science Tower, 200 Lothrop Street
Pittsburgh, PA 15261

Phone: 412-383-8044

Fax: 412-648-1945


B.S. (Biology), University of Science and Technology of China, Hefei, P.R. China, 2003

Ph.D. (Biochemistry and Molecular Biology), University of Science and Technology of China, Hefei, P.R. China, 2008

Research Areas
Structural Pharmacology
Receptor Pharmacology
Signal Transduction
Photo of Cheng Zhang, PhD

My group focuses on the study of model G protein-coupled receptors (GPCRs) to elucidate the molecular mechanisms of receptor signaling and to advance our understanding of their pharmacology. GPCRs are a family of cell surface receptors with over 700 members. They transduce signals from extracellular signaling molecules, including hormones and neurotransmitters, to intracellular effectors in order to mediate and regulate a broad spectrum of physiological and pathological processes. GPCRs have been heavily investigated in the pharmaceutical industry, and they constitute 30-40% of current drug targets. Yet the mechanistic details of GPCR signal transduction across the cell membrane are largely poorly understood, in part due to the extraordinary complexity of receptor conformational states associated with different ligands and different signaling outputs. My lab is trying to explore the molecular mechanisms underlying the signal transduction of certain GPCRs through combinatorial approaches, including structural biology approaches, spectroscopic tools, and molecular pharmacology approaches.

Current efforts are directed at elucidating the atomic structures of several GPCRs that function in inflammation and calcium metabolism, in complex with their ligands as currently used drugs or potential drug candidates. These structures will reveal the molecular basis of the action of the ligands, as well as the structural elements of receptors that are involved in signal transduction. This information will guide further biophysical and computational studies performed in my lab, or through collaborations, to explore the dynamics and conformational versatility of these receptors and guide structure-based drug design for the development of drugs with improved pharmacological properties. Long-term goals also include the structural characterization of these receptors in complex with their signaling effectors and the characterization of the different pharmacological behaviors of these receptors when coupled with different signaling effectors. The resulting information will greatly advance our understanding of GPCR signaling and GPCR molecular pharmacology, and will be quite valuable for designing new pharmaceuticals used in the treatment and management of inflammatory diseases, bone diseases and cancer.

Important Publications
Weichert D, AC Kruse, A Manglik, C Hiller, C Zhang, H Hübner, BK Kobilka and P Gmeiner.  Covalent agonists for studying G protein-coupled receptor activation.  PNAS 111:10744,10748, 2014.
Zocher M, C Bippes, C Zhang and DJ Muller.  Single-molecule force spectroscopy of G-protein-coupled receptors.  Chem Soc REv 42:7801-7815, 2013.
Zhang C, Y Srinivasan, DH Arlow, JJ Fung, D Palmer, Y Zhang, HF Green, A Pandey, RO Dror, DE Shaw, WI Weis, SR Coughlin and BK Kobilka.  High-resolution crystal structure of human protease-activated receptor 1.  Nature 492:387-392, 2012.
Zocher M, C Zhang, SGF Rasmussen, BK Kobilka and DJ Muller.  Cholesterol increases kinetic, energetic, and mechanical stability of the human ß2 adrenergic receptor.  PNAS 109:E3463-E3472, 2012.
Rosenbaum DM, C Zhang, J Lyons, R Holl, D Aragao, DH Arlow, SGF Rasmussen, H Choi, BT DeVee, RK Sunahara, PS Chae, SH Gellman, RO Dror, DE Shaw, WI Weis, M Caffrey, P Gmeiner and BK Kobilka.  Structure and function of an irreversible agonist-ß2 adrenoceptor complex.  Nature 469:236-240, 2011.
Zhang C, L Liu, H Xu, Z Wei, Y Wang, Y Lin and W Gong.  Crystal structures of human IPP isomerase:  New insights into the catalytic mechanism.  J Mol Biol 366:1437-1446, 2007.

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