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

Education

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
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. My lab is trying to explore the molecular mechanisms underlying the signal transduction of certain GPCRs through multiple approaches in structural biology, biophysics, pharmacology and cell biology.
 
Currently we focus on two groups of GPCRs, the lipid GPCRs involved in asthma and the neurotransmitter GPCRs involved in neurological disorders. Short-term research goals include obtaining atomic structures of these GPCRs in complex with various ligands and signaling partners. The structural information guides our pharmacological and cell-based studies to dissect the novel mechanisms underlying drug action and receptor signaling. In addition, we also perform structure-based drug design studies to develop novel GPCR ligands and develop new GPCR antibodies for drug development.
 
Link to our publications:  https://www.ncbi.nlm.nih.gov/myncbi/1Xqbv7vTlyh5w/bibliography/public/

Journal Articles

Qi X, H Liu, B Thompson, J McDonald, C Zhang and X Li. Structure of human smoothened coupled to a heterotrimeric Gi protein. Nature 571:279-283, 2019.
Masureel M, Y Zou, L-P Picard, E van der Westhuizen, JP Mahoney, JPGLM Rodrigues, TJ Mildorf, RO Dror, DE Shaw, M Bouvier, E Pardon, J Steyaert, RK Sunahara, WI Weis, C Zhang and BK Kobilka.  Structural insights into binding specificity, efficacy and bias of a ß2AR partial agonist.  Nature Chemical Biology 14:1059-1066, 2018.
Wang L, D Yao, RNVK Deepak, H Liu, Q Xiao, H Fan, W Gong, Z Wei and C Zhang. Structures of the human PGD2 receptor CRTH2 reveal novel mechanisms for ligand recognition. Molecular Cell 72:48-59 e4, 2018.
Liu H, HR Kim, RNVK Deepak, L Wang, KY Chung, H Fan, Z Wei and C Zhang. Orthosteric and allosteric action of the C5a receptor antagonists. Nature Structural & Molecular Biology 25:472-481, 2018.
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.

Sponsored Research

Structure, pharmacology and signaling of G protein-coupled receptors (GPCRs) in inflammation - 8/1/2018 - 7/31/2023
NIH - R35 GM128641
Structural Basis of PTH Receptor Function - 4/1/2018 - 3/31/2022
NIH - R01DK116780