Faculty

Tianyi Wang, PhD Assistant Professor E-mail: tywang@pitt.edu Phone: 412-383-9916 Fax: 412-383-8926 Address: 723 Parran Hall 130 DeSoto Street Pittsburgh, PA 15261

Education

BA; Beijing Medical University
DPhil; The Ohio State University

Research Interests

Hepatitis C Virus, Innate Immunity, Proteomics, Host-pathogen interaction.

Research Summary

Hepatitis C virus entry: The overall interest of the laboratory is to understand the fundamental mechanisms by which HCV infects human hepatocytes. Current research focus is to characterize the tight junction (TJ) protein Occludin-mediated HCV entry process. We have recently demonstrated that Occludin is a required cellular factor for HCV entry. Accumulated evidence from us also suggests that HCV probably enters cells at TJ where multiple TJ proteins assemble into a complicated molecular architecture. As a result of viral infection, the expression and localization of TJ proteins undergo dynamic changes, which could contribute to some of the pathological changes in infected livers. We are assessing the structural requirement for Occludin to be a functional HCV co-receptor of viral entry. Besides, various new infection systems are being developed in the lab, as it will significantly advance HCV vaccine development and drug discovery if small animal models and cell systems that more closely resemble primary human hepatocytes can be developed.

Mapping HCV interactome and secretome: This area of research was initially supported by a small institutional fund for two years, and then expanded to its current scope. We plan to map the entire HCV interacting network as well as the proteins secreted by liver cells upon HCV infection using a quantitative mass spectrometry-based proteomics approach. We believe that identified host factors contain information that is important to understanding of both HCV lifecycle and HCV pathogenesis. Our preliminary results have revealed that the critical de novo lipogenic enzyme, fatty acid synthase (FASN), was upregulated by HCV infection and secreted into supernatant. We are currently evaluating if this upregulation results in altered lipid profile. Since FASN is known to be upregulated in a number of tumors, our project has a close relevance to HCV-associated liver diseases including steatosis (accumulation of fat in liver cells) and hepatocellular carcinoma.

Immune mechanisms harnessing HIV infection: This new exploratory project is to understand if a novel group of dsRNA-editting enzymes function to introduce mutations to human immunodeficiency virus 1 (HIV-1) genome RNA. The hypothesis to be tested is that these enzymes play a pivotal role as part of the innate immune defense mechanisms to control the virus infection. Besides HIV-1, HCV and Influenza A virus will be tested as well in cell culture systems.

Systems biology of TLR signal transduction pathway: This project is funded by a NIH R21 grant for two years. The goal is to apply a newly developed mass spectrometry-based approach to systematically elucidate components of the critical innate immune signaling pathway mediated by a number of TLR receptors.

Recent Publications

• Wang, T.Y., Lafuse, W.S., and Zwilling, B.S. (2000) The regulation of Toll-like receptor 2 expression by Macrophages following Mycobacterium avium infection. J. Immunol. 165:6308-6313.

• Wang, T.Y., Lafuse, W.S., and Zwilling, B.S. (2001) NFkB and Sp1 elements are necessary for maximal transcription of Toll-like Receptor 2 Induced by Mycobacterium avium. J. Immunol. 167:6924-6932.

• Wang, T.Y., Lafuse, WS., Kiyoshi Takeda, Shizuo Akira, and Zwilling, B.S. (2002) Rapid Chromatin Remodeling of TLR2 Promoter during Infection of Macrophages with Mycobacterium Avium. J. Immunol. 169:795-801.

• Wang, T.Y., Gu, S, Ronni, T, Du, Y., Chen, X. (2005) Dual tagging proteomic approach in studying immune signaling transduction. J. Proteome Res. 4:941-949.

• Wang, T.Y., Chuang, T, Ronni, T, Gu, S, Chen X. (2006) Fliih negatively modulates the
TLR pathway. J, Immunol. 176:1355-1362.

• Yu-Chun, D., Gu, S., Zhou, J., Wang, T., Cai, H., MacInnes, M.A., Bradbury, M., and Chen, X. (2006) The dynamic alterations of H2AX complex during DNA repair detected by a proteomic approach reveal the critical roles of Ca2+/calmodulin in the ionizing radiation induced cell cycle arrest. Mol. Cell. Proteomics 5:1033-1044.

• Yang, W., C. Qiu, N. Biswas, J. Jin, S. C. Watkins, R.C. Montelaro, C.B.Coyne, and T. Wang. (2008) Correlation of the tight junction-like distribution of Claudin-1 to the cellular tropism of HCV. J. Biol. Chem. 283(13):8643-53.

• GU, S*., Wang, TY*., X. Chen. (2008). Quantitative proteomic analysis of LPS-induced differential immune response associated with TLR4 Polymorphisms by multiplex amino acid coded mass tagging. Proteomics. 8(15):3061-3070. (equal contribution).

• Yang, W., B. Hood, S. Chadwick, S. Liu, S.C. Watkins, G. Luo, T. Conrads, and TY.Wang. (2008). Fatty acid synthase is upregulated during HCV infection and regulates HCV entry and production. Hepatology. 48(5):1396-403.

• Liu, S., Yang, W., Shen, L., Turner, J., Coyne, C., TY.Wang. (2009). Tight junction proteins Claudin-1 and Occludin control Hepatitis C Virus entry and are downregulated during infection to prevent superinfection. Spotlight article. J. Virol. 83(4):2011-4. Epub 2008 Dec 3.

• Mukherjee,A., Morosky, S.A., Shen, L., Weber, C.R., Turner, J.R., Kim, K.S., TY. Wang, and Carolyn B. Coyne. (2009) Retinoic-acid-inducible gene-1 (RIG-I) associates with the actin cytoskeleton via CARD-dependent interactions. J. Biol. Chem. Jan 3. [Epub ahead of print].

• Chang K, Wang T, Luo G. (2009) Proteomics study of the hepatitis C virus replication complex. Methods Mol Biol. 510:185-93.

Dr. Wang's Lab

Staff

Wayne Kuo; Research III 724 Parran Hall, 412-648-1690, wak15@pitt.edu

Students
Biswas, Nabanita 724 Parran Hall, 412-648-1690, nab31@pitt.edu

Postdoctoral Fellow
Liu, Shufeng 724 Parran Hall, 412-648-1690, shl57@pitt.edu

Past Lab Members
Wei Yang, PhD, Postdoctoral fellow, 2006-2008 Current position: Associate Professor, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing, China.
Chao Qiu, BM, MS, Research Associate, 2006-2007 Current position: Assistant Investigator, Institutes of Biomedical Sciences at Fudan University, Shanghai, China.