Associate Professor and Director of MS Program

Email: 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; 1996
DPhil; The Ohio State University; 2001


Research Interests

Hepatitis C Virus Entry, Innate Immunity, Viral 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. We also hope to eventually be able to develop entry blockers to stop HCV infection.

HCV Viral Proteomics: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. In a continuation of this effort, we are now collaborating with Dr. William Bigbee (Director, Mass Spectrometry Platform and Cancer Biomarkers Facility, University of Pittsburgh Cancer Institute) and moving toward patient-derived plasma samples for immunopeptidome identification. Ultimately, these studies may shed new insights on the understanding the development of liver disease and provide potential cancer biomarkers of HCV-associated hepatocellular carcinoma (HCC).

Dengue virus entry and drug screening: We have recently converted a laboratory observation that Dengue virus infection causes cell death into a drug screening assay and have identified two compounds that potently block Dengue infection. This project involves collaboration with Dr. Ernesto Marques (Center for Vaccine Research, University of Pittsburgh) and Dr. Nicholas Sluis-Cremer (Department of Medicine, University of Pittsburgh). The ultimate goal of these efforts is to create novel therapeutics in treating viral infection. We also interested in understanding the entry process of Dengue virus into cells using multiple infection systems.

Recent Publications 

• Yang, W., C. Qiu, N. Biswas, J. Jin, S. C. Watkins, R.C. Montelaro, C.B.Coyne, and T. Wang. Correlation of the tight junction-like distribution of Claudin-1 to the cellular tropism of HCV. J. Biol. Chem. 2008, 283(13):8643-53.
• GU, S*., Wang, TY*., X. Chen. Quantitative proteomic analysis of LPS-induced differential immune response associated with TLR4 Polymorphisms by multiplex amino acid coded mass tagging. Proteomics. 2008, 8(15):3061-3070. (equal contribution).

• Yang, W., B. Hood, S. Chadwick, S. Liu, S.C. Watkins, G. Luo, T. Conrads, and TY.Wang. Fatty acid synthase is upregulated during HCV infection and regulates HCV entry and production. Hepatology. 2008, 48(5):1396-403.
• Liu, S., Yang, W., Shen, L., Turner, J., Coyne, C., TY.Wang. Tight junction proteins Claudin-1 and Occludin control Hepatitis C Virus entry and are downregulated during infection to prevent superinfection. Spotlight article. J. Virol. 2009, 83(4):2011-4.
• Mukherjee,A., Morosky, S.A., Shen, L., Weber, C.R., Turner, J.R., Kim, K.S., TY. Wang, and Carolyn B. Coyne. Retinoic-acid-inducible gene-1 (RIG-I) associates with the actin cytoskeleton via CARD-dependent interactions. J. Biol. Chem. 2009, 83(4):2011-4.
• Chang K, Wang T, Luo G. Proteomics study of the hepatitis C virus replication complex. Methods Mol Biol. 2009, 510:185-93.
• Liu X, TY. Wang, T, Wakita, W. Yang. Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology. 2010, 398(1):57-67.
• Liu, S., Kuo, W., Yang, W., Gibson, G., Dorko, K., Watkins, S., Strom, S., TY.Wang*. Human Occludin extracellular loop 2 dictates HCV entry. Virology. 2010 Nov 10;407(1):160-70. PMID: 20822789. (*cover image)
• Ramcharran D, Wahed AS, Conjeevaram HS, Evans RW, Wang T, Belle SH, Yee LJ; for the Virahep‐C Study Group. Associations between serum lipids and hepatitis C antiviral treatment efficacy. Hepatology. 2010 Sep;52(3):854-63.
• Ramcharran D, Abdus W, Conjeevaram H, Evans R, T. Wang, Belle S, L.J.Yee. Serum lipids and their associations with viral levels and liver disease severity in a treatment naïve chronic hepatitis C type 1 infected cohort. J Viral Hepat. 2011, 18, e144-e152. PMID: 21070504
• Mukherjee A, Morosky S, Delorme-Axford E, Dybdahl-Sissoko N, Oberste M, T Wang, and C.B. Coyne . The Coxsackievirus 3Cpro protease cleaves MAVS and TRIF to attenuate host type I interferon and apoptotic signaling. 2011. PLoS Pathogen 7(3):e1001311. doi: 10.1371/journal.ppat.1001311.
• Biswas N, Liu S, Ronni T, Aussenberg S, Liu W, Fujita T, TY. Wang. 2011. The Ubiquitin-like Protein PLIC-1 or Ubiquilin 1 Inhibits TLR3-TRIF Signaling. PLoS ONE 6(6): e21153. doi:10.1371/journal.pone.0021153.
• Nabanita Biswas; Tianyi Wang; Ming Ding; Ashwin Tumne; Yue Chen; Qingde Wang; Phalguni Gupta. ADAR1 is a Novel Multi Targeted Anti HIV-1 Cellular Protein. 2012. Virology. Jan 20;422(2):265-77.
• Liu S, McCormick KD, Zhao W, Zhao T, Fan D, Wang T. Human apolipoprotein E peptides inhibit hepatitis C virus entry by blocking virus binding. Hepatology. 2012 Feb 15. doi: 10.1002/hep.25665. [Epub ahead of print]
• Si Y, Liu S, Liu X, Jacobs JL, Cheng M, Niu Y, Jin Q, Wang T, Yang W. A human claudin-1 derived peptide inhibits hepatitis C virus entry. Hepatology. 2012 Mar 1. doi: 10.1002/hep.25685. [Epub ahead of print]
• McCormick KD, Liu S, Jacobs JL, Marques ET Jr, Sluis-Cremer N, Wang T. Development of a Robust Cytopathic Effect-Based High-Throughput Screening Assay to Identify Novel Inhibitors of Dengue Virus. Antimicrob Agents Chemother. 2012 Jun;56(6):3399-401.

                                                                                       
Dr. Wang's Lab

Staff
Liu, Shufeng; 724 Parran Hall, 412-628-1690
Zhoo, Jianhua; zho@pitt.edu; 724 Parran Hall, 412-628-1690