Lorne Tyrrell, MD, PhD
Li Ka Shing Institute of Virology
Department of Medical Microbiology and Immunology
6010 Katz Centre for Health Research
Edmonton, AB T6G 2E1
Ph : (780) 492-6018/492-8415
Fx : (780) 492-5304
- Professor, Dept. of Medical Microbiology & Immunology
The research in my laboratory is focused on the study of hepatitis B virus (HBV) and hepatitis C virus (HCV). We have a major interest in therapeutic approaches for the treatment of chronic viral hepatitis – either HBV or HCV. Our work on HBV has utilized the Pekin duck model to identify and verify nucleoside analogues with specific activity for hepadnaviruses (duck and human HBV). Our work has led to the licensing of the first oral antiviral for HBV – lamivudine – which is used worldwide. However, single nucleotide changes in the polymerase gene leads to lamivudine-resistant viruses; hence, newer agents that are less prone to resistance or the combination of antivirals to prevent resistance are additional approaches to therapy.
Most recently we have focused on the covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. The cccDNA has a long half-life and is the source of viral reactivation when therapy with nucleoside analogues is stopped. Current work in the laboratory is examining ways to prevent reactivation using zinc finger proteins targeted to cccDNA.
Our laboratory collaborated with Dr. Norm Kneteman’s laboratory to develop mice with chimeric human/mouse livers. These mice can be infected with either HBV or HCV. We have a particular interest in studying the innate immune response in the human hepatocytes in response to HCV infection of the chimeric mice. We believe the differences seen in the innate immune response may determine the outcome – persistence or clearance of HCV infection.
The laboratory is in the Centre of Excellence for Viral Hepatitis Research (CEVHR) located on the 6th floor of the Heritage Medical Research Centre at the University of Alberta and will move early in 2009 to new laboratory space on the 6th floor of HRIF West.
- Dr. Bill Addison (Research Associate)
- Bonnie Bock (Administrative Staff)
- Ran Chen (Graduate Student)
- Cory Ebeling (PDF)
- Karl Fischer (Research Scientist)
- Dr. Michael Joyce (Research Associate)
- Gerald Lachance (Technologist)
- Suellen Lamb (Histologist)
- Dr. Aviad Levin (PDF)
- Darci Loewen-Dobler (Support Staff)
- Dr. Rineke Steenbergen (Research Associate)
- Justin Shields (Technician)
- Karyn Barry-Wynne (Technician)
- Tiing Tiing Chua (Graduate Student)
- Connie Le (Graduate Student)
- Leticia Wilson (Clinical Research Associate)
- Dr. Qingxia Yao (PDF)
- Sacci JB Jr., Alam U, Douglas D, Lewis J, Tyrrell DLJ, Azad AF, and Kneteman NK. Plasmodium falciparum infection and exoerythrocytic development in mice with chimeric human livers. Int. J. Parasitol. 2006 Mar:36 (3):353-60.
- Walters KA, Joyce MA, Thompson JC, Proll S, Wallace J, Smith MW, Furlong J, Tyrrell DLJ, and Katze MG. Application of functional genomics to the chimeric mouse model of HCV infection: optimization of microarray protocols and genomics analysis. Virol Journal 2006; 3:37.
- Walters KA, Joyce MA, Thompson JC, Smith MW, Yeh MM, Proll S, Zhu LF, Gao TJ, Kneteman N, Tyrrell DLJ, and Katze MG. Host-specific Response to HCV Infection in the Chimeric SCID/Alb-upA Mouse Model: Role of the innate Antiviral Immune Response. PLoS Pathog. 2006 Jun;2(6):591-602.
- Kneteman NM, Howe AYM, Gao T, Lewis J, Pevear D, Lund G, Douglas D, Mercer D, Tyrrell DLJ, Immermann F, Chaudhary I, Speth J, Villano SA, O'Connell J, and Collett M. HCV796: a selective NS5B polymerase inhibitor with potent antiHCV activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis C virus. Hepatology. Accepted 2008
- Zimmerman KA, Fischer KP, Joyce MA, and Tyrrell DLJ. Zinc finger proteins designed to specifically target duck hepatitis B virus covalently closed circular DNA inhibit viral transcription in tissue culture. J Virology 2008 Aug;82(16):8013-21.
- Joyce MA, Walters KA, Lamb S, Yeh MM, Kneteman N, Doyle J, Katze MG, and Tyrrell DLJ. HCV induces oxidative and ER stress, and sensitizes infected cells to apoptosis in SCID/Alb-uPA mice. PlosPathogens. Conditionally Accepted 2008.
- Zimmerman, K.A., Fischer, K.F., Joyce, M.A., and Tyrrell, D.J.L. (2007) Hepatitis B Virus-binding Polypeptides and Methods of Use Thereof. U.S. Patent Application 60/972,644.
- 5,039,667 USA.
Antiviral therapy for hepatitis B with 2',3'-dideoxypurine nucleosides. Tyrrell; David L. J.; Robins; Morris J. ; Suzuki; Satoru. Issue Date: August 13, 1991
- 6,509,514 USA.
Chimeric animal model susceptible to human hepatitis C virus infection. Kneteman; N. M.; Tyrrell; D. L.; Mercer; D. F. Issue Date: January 21, 2003.