Dr. Waris received his Ph.D. degree in Biochemistry from Aligarh Muslim University, Aligarh, India in 1999. He completed his postdoctoral fellowship on viral hepatitis B and C in the laboratory of Dr. Aleem Siddiqui at the University of Colorado Health Sciences Center (UCHSC), Denver. Dr. Waris was appointed as an Instructor in the Department of Microbiology at UCHSC, and later moved to Division of Infectious Diseases, Department of Medicine at University of California, San Diego, in 2005, as Assistant Project Scientist. Dr. Waris joined the Department of Microbiology and Immunology at Rosalind Franklin University of Medicine and Science on March 1, 2007, as Assistant Professor.
Chronic liver disease due to infection with hepatitis C virus (HCV) is a major global health problem that currently affects 170 million people. Persistent HCV infections can progress to chronic hepatitis, liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. At present, antiviral therapies are limited and prophylactic vaccines are not available, partially due to the lack of a non-primate animal model and an efficient cell culture system. Our work combines molecular biology, genetic tools, biochemical techniques, cell biology and recently developed robust HCV cell culture infection systems to define the molecular mechanisms of viral replication and the determinants of the HCV-host interaction. Specifically, we focus on characterizing the ribonucleoprotein (RNP) complexes to identify the potential anti-viral targets for therapeutic intervention. Our studies also provided the first compelling evidence that HCV induces oxidative stress via calcium signaling and has deep impact on liver failure and incidence of cancer. We demonstrated the molecular mechanisms of activation of several key players including oncogenic transcription factors and proinflammatory molecules in response to oxidative stress that can be used as a drug targets in liver oncogenesis. Our research is aimed at delineating the mechanism by which viral infection induces 1) liver fibrosis; 2) inflammation and liver oncogenesis; 3) metabolic disorders such as steatosis and insulin resistance; 4) HCV replication and assembly.These studies will open new avenues for antiviral therapy.
Burdette D, Haskett A, Presser L, McRae S, Iqbal J, and Waris, G. 2012. Hepatitis C virus activates interleukin-beta 1 via caspase-1-inflammasome complex. J. Gen. Virol. 93:235-246.
Presser L, Haskett A, and Waris G. Hepatitis C virus-induced furin and thrombospondin-1 activate TGF-β1: Role of TGF-β1 in HCV replication. Virology, 412:284-296. 2011.
Burdette D, Olivarez M, Waris G. Activation of transcription factor Nrf2 by hepatitis C virus induces the cell-survival pathway. J. Gen. Virol. 91(3):681-690. 2010.
Nasimuzzaman, M., Waris, G., Mikoloan, D., Stupack, D.G. and Siddiqui, A. “A Hepatitis C virus stabilizes hypoxia-inducible factor 1a and stimulates the synthesis of vasculas endothelial growth factor.” J. Virology. 81: 10249-10257, 2007. (N.M. and *G.W contributed equally to this work)
Waris, G., Felmlee, D.J., Negro, F., and Siddiqui, A. “Hepatitis C virus infection induces proteolytic cleavage of sterol regulatory element binding proteins (SREBP's) and their phosphorylation via oxidative stress." J. Virology. 81:1-9, 2007.
Waris, G., Khan, M. A., Khan, S., and Alam, K. Binding of superoxide-modified DNA by cancer antibodies. J. Exp. Clin. Cancer Res. 26: 499-504. 2007
Waris, G. and H. Ahsan. “Reactive oxygen species: Role in the development of cancer and various chronic conditions” Journal of Carcinogenesis, 5:1-8, 2006 (Review).
Waris, G. and A. Siddiqui. “Hepatitis C virus-induced oxidative stress activates cyclooxygenase-2 (Cox-2): Role of prostaglandin E 2 in RNA replication,” J. Virology. 79:9725-9734, 2005.
Tardif, K. D., G.Waris, and A. Siddiqui. “Hepatitis C virus, ER stress, and oxidative stress,” Trends in Microbiol.,13 (4):159-164, 2005 (Review).
Waris, G. , J. Turkson, T. Hassanein, and A. Siddiqui. “Hepatitis C Virus constitutively activates STAT-3 via oxidative stress: Role of STAT-3 in HCV replication,” J. Virolology. 79:1569-1580, 2005.
Waris G. , and K. Alam. “Immunogenicity of superoxide modified-DNA: studies on induced antibodies and SLE anti-DNA antibodies, “ Life Sci., 75:2633-2642, 2004.
Waris, G. , S. Sarker, and A. Siddiqui. “Two-step affinity purification of the hepatitis C virus ribonucleoprotein complex,” RNA, 10: 321-329, 2004.
Waris, G. , A. Livolsi, V. Imbert, J. F. Peyron, and A. Siddiqui. HCV subgenomic replicons and NS5A protein activate NF-kB via tyrosine phosphorylation of IkBa and its degradation by calpain protease, “J. Biol. Chem.,278: 40778-40787, 2003.
Waris, G. and A. Siddiqui, A. “Regulatory mechanisms of viral hepatitis B and C,”J. Biosciences, 28: 311-321, 2003 (Review).
Waris, G. K.Tardif,and A. Siddiqui. “ER stress: HCV NS5A induces an ER-nucleus signal transduction pathway and activates NF-kB and STAT-3,” Biochem. Pharmacol., 64: 1425-1430, 2002 (Review).
Waris, G. and A. Siddiqui. “Interaction between STAT-3 and HNF-3 Leads to the activation of liver-specific hepatitis B virus enhancer 1 function,” J. Virology. 76:2721-2729, 2002.
Waris, G. , K-W. Huh, and A. Siddiqui. “Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kB via oxidative stress,” Mol. Cell. Biol., 21: 7721-7730, 2001.
Gong, G., G *. Waris,R.Tanveer, and A. Siddiqui. “Human hepatitis C virus NS5A protein alters intracellular calcium level, induces oxidative stress, and activates STAT-3 and NF-kB,” Proc. Natl. Acad. Sci. U.S.A., 98: 9599-9604, 2001(G.G. and *G. W. contributed equally to this work).
Waris, G. , H. Ahsan, and K. Alam. “Evidence for the possible involvement of superoxide modified DNA in the etiopathogenesis of systemic lupus erythematosus,” J. Biochem. Mol. Biol. & Biophys., 4: (1) 9-16, 2000.
Waris, G. and K. Alam. “Attenuated antigenicity of ribonucleoproteins modified by reactive oxygen species,” Biochem. Mol. Biol. Int., 45: 33-45, 1998.