Department of Internal Medicine
Warren Schmidt, M.D., Ph.D.
My laboratory at the University of Iowa and Veteran’s Affairs Center has studied the detection and pathogenesis of hepatitis C virus since 1996. In early 2002 we shifted our interests to investigate oxidative stress, protective antioxidative enzymes, and the role of antioxidants during chronic HCV infection and inflammation. We reported that HCV tightly regulated the inducible antioxidative enzyme, heme oxygenase-1 (HO-1) and that the regulation likely contributes to viral induced hepatocyte injury. More recently, we reported that HO-1 overexpression or induction attenuates viral replication in HCV expressing cell lines. Finally, we just published a paper showing that biliverdin, the primary tetrapyrrole enzymatic product of heme oxidation, directly and competitively inhibits the hepatitis C virus NS3/4A protease. These exciting findings suggest that biliverdin or other heme metabolites would be useful antiprotease agents to treat chronic HCV infection.
Our current work focuses on development of new protease inhibitors using biliverdin or active derivatives. We are also studying the potential effects of porphyrins and metabolic products on hepatic injury and inflammation.
Honors, Awards, and Organizations
- American Association for Study of Liver Diseases
- America's Top Doctors (Castle, Connolly Medical, Ltd.)
- Who's Who in America (Science & Engineering)
- Zhu Z, Wilson AT, Luxon BA, Brown KE, Mathahs MM, Bandyopadhyay S, McCaffrey AP and Schmidt WN. Biliverdin inhibits Hepatitis C virus NS3/4A protease activity: Mechanism for the antiviral effects of heme oxygenase? Hepatology(52):1897-1905, 2010.
- Marquez RT, Bandyopadhyay S, Wendlandt EB, Keck K, Hoffer BA, Icardi MS, Christensen RN, Schmidt WN and McCaffrey AP. MicroRNA expression levels correlate with clinical parameters during chronic Hepatitis C viral infection in humans. Laboratory Investigation (90):1727-1736, 2010.
- Zhu Z, Wilson AT, Gopalakrishna K, Brown KE, Luxon BA and Schmidt WN. Hepatitis C virus core protein enhances telomerase activity in Huh7 cells. Journal of Medical Virology 82:239-248, 2010 PMID 20029802.
- Kayali Z, Herring J, Baron P, Franco E, Ojogho O, Smith J, Watkins G, Smith D, Lamin V, Hoang T, Sharma R, Mathahs M, Sowers L, Brown KE and Schmidt WN. Increased plasma nitric oxide, L-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction. Journal of Gastroenterology and Hepatology 24(6):1030-1037, 2009 PMID 19226382.
- Zhu Z, Wilson AT, Mathahs MM, Wen F, Brown KE, Luxon BA and Schmidt WN. Heme oxygenase-1 suppresses hepatitis C virus replication and increases resistance of hepatocytes to oxidant injury. Hepatology 48:1430-1439, 2008.