Michael Houghton, PhD
Dept. of Medical Microbiology & Immunology
University of Alberta
Faculty of Medicine & Dentistry
6-010 Katz Group-Rexall Centre for Health Research
T6G 2E1 Edmonton, AB
Ph : (780) 248-1888
Fx : (780) 492-7521
- Canada Excellence Research Chair in Virology
- Professor, Dept. of Medical Microbiology & Immunology
Hepatitis C virus (HCV)
Research is aimed at developing a HCV vaccine that can protect against the many heterogeneous forms of this virus that occur globally. Every year, many hundreds of thousands of people become infected with HCV world-wide and so there is an urgent need to develop a safe, efficacious vaccine that can be delivered conveniently to both the developed and developing worlds. Previously, vaccine candidates designed to elicit cross-neutralizing antibodies or cross-reactive T cell responses have been shown capable of partially protecting animals from experimental viral challenge but a number of key scientific issues remain. One of these concerns elucidating a system for the efficient synthesis of the envelope glycoproteins gpE1 and gpE2 and relating their structural properties with the ability to elicit cross-neutralizing antibodies. Such antibodies will be measured in cell cultures producing HCV as well as in the novel SCID-uPA mouse infection model developed by Professors Kneteman & Tyrrell and colleagues at the University of Alberta. A second key goal relates to defining immunological correlates of protection against HCV infection and will involve assessing the relative roles of neutralizing antibodies and CD4+ helper and CD8+ cytolytic T cells in the protective immune response. Mechanisms through which chronic, persistent viral infection suppresses the activity of specific cellular immune responses and co-exists despite the presence of neutralizing antibodies will also be addressed with a view to developing a role for vaccination along with antiviral drugs in treating pre-existing infected patients.
The current standard-of-care for HCV patients is the combined administration of interferon-alpha and ribavirin with which approximately 50% of patients are cured. The mechanisms of action of these drugs and newer antivirals will be investigated with a view to improving their effectiveness.
Hepatitis B virus (HBV)
Like HCV, HBV is a major cause of morbidity and mortality around the world. Following the pioneering work of Professor Lorne Tyrrell and colleagues at the University of Alberta, a series of nucleoside analogues are now available that inhibit the viral reverse transcriptase resulting in effective suppression of viremia and concomitant amelioration of disease. However, the supercoiled viral DNA genome persists in many treated patients meaning that they require prolonged treatment and with a risk of drug-resistant viruses emerging. Therapeutic vaccination strategies are being investigated in order to boost cellular immune responses capable of eradicating infected hepatocytes as possible adjunct therapy along with antiviral drugs.
Viral etiology of inflammatory disease - the search for causative viral pathogens
Many diseases of man like alzheimer’s, multiple sclerosis, inflammatory bowel disease, cryptogenic encephalitis, cryptogenic hepatitis/cirrhosis, certain types of diabetes, epilepsy, rheumatoid arthritis and others could be caused or exacerbated by an acute or persistent viral infection by various infectious pathogens. Working with leading University of Alberta clinical groups and meta-genomics researchers already investigating some of these diseases ( Professors Mason, Wong, Fedorak & Van Zanten ), collaborative research will be conducted attempting to identify contributing viral etiologies for some of these major conditions using genomic, proteomic and immunological analyses.
- Darren Hockman (Lab Manager/Biological Technologist)
- Chao Chen (Laboratory Technician)
- Ervin Hou (Laboratory Technician)
- Anita Dahiya (Animal Technician/Laboratory Assistant)
- Lesley Poirier (Animal Technician/Laboratory Assistant)
- Janelle Johnson (Animal Technician/Laboratory Assistant)
- Dr. Amir Landi (PDF)
- Dr. Deanna Santer (PDF)
- Dr. Mohammed Sarhan (PDF)
- Dr. Anwar Anwar-Mohamed (PDF)
- Dr. Shaon Joy (PDF)
- Dr. Ryan Fradette (PDF)
- Dr. Nataraj Pagadala (PDF)
- Dr. Owen Scadeng (PDF)
- Dr. Michael Logan (Research Associate)
- Dr. John Law (Research Associate)
- Dr. Rakesh Bhat (Research Associate)
- Dr. Holly Freedman (Research Associate)
- Jason Wong (PhD Student)
- Darci Loewen-Dobler (Part-time Lab Assistant)
- Amir Fakheri (Casual Animal Technician)
- Dr. Wendy Magee (Operations Manager)
- Joyce Naumann (Administrative Assistant)
I am looking for people to join my lab. See here.
Hepatitis C Virus
Law JL, Chen C, Wong J, Hockman D, Santer DM, Frey SE, Belshe RB, Wakita T, Bukh J, Jones CT, Rice CM, Abrignani S, Tyrrell DL, Houghton M. (2013) A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans. PLoS One. 8(3):e59776.
Houghton M. (2012) Chimp virus makes a savvy vaccine vector. Sci. Transl. Med. 4:115fs1.
Meunier JC, Gottwein JM, Houghton M, Russell RS, Emerson SU, Bukh J, Purcell RH. (2011) Vaccine-induced cross-genotype reactive neutralizing antibodies against hepatitis C virus. J. Infect. Dis. 204:1186-90.
Stamataki Z, Coates S, Abrignani S, Houghton M, McKeating, J. (2011) Immunization of human volunteers with Hepatitis C virus envelope glycoproteins elicits antibodies that cross-neutralize heterologous virus strains. J. Infect. Dis. 204:811-3.
Houghton M. (2011) Prospects for prophylactic and therapeutic vaccines against the hepatitis C viruses. Immunol. Rev. 239:99-108.
Frey SE, Houghton M, Coates S, Abrignani S, Chien D, Rosa D, Pileri P, Ray R, Di Bisceglie AM, Rinella P, Hill H, Wolff MC, Schultze V, Han JH, Scharschmidt B, Belshe RB. (2010) Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults. Vaccine. 28:6367-73.
Ray R, Meyer K, Banerjee A, Basu A, Coates S, Abrignani S, Houghton M, Frey SE, Belshe RB. (2010) Characterization of antibodies induced by vaccination with hepatitis C virus envelope glycoproteins. J. Infect. Dis. 202:862-6.
Drane D, Maraskovsky E, Gibson R, Mitchell S, Barnden M, Moskwa A, Shaw D, Gervase B, Coates S, Houghton M, Basser R. (2009) Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX vaccine: a phase I study in healthy volunteers. Hum. Vaccin. 5:151-7.
Houghton M. (2009) The long and winding road to the identification of the hepatitis C virus. J. Hepatol. 51:939–48.
Houghton M. (2009) Discovery of the hepatitis C virus. Liver Int. 29 Suppl 1:82-8. Review.
Lin Y, Kwon T, Polo J, Zhu YF, Coates S, Crawford K, Dong C, Wininger M, Hall J, Selby M, Coit D, Medina-Selby A, McCoin C, Ng P, Drane D, Chien D, Han J, Vajdy M, Houghton M. (2008) Induction of broad CD4+ and CD8+ T-cell responses and cross-neutralizing antibodies against hepatitis C virus by vaccination with Th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2 and nonstructural proteins 3, 4, and 5. J. Virol. 82:7492-503.
Bowen DG, Shoukry NH, Grakoui A, Fuller MJ, Cawthon AG, Dong C, Hasselschwert DL, Brasky KM, Freeman GJ, Seth NP, Wucherpfennig KW, Houghton M, Walker CM. (2008) Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection. J. Virol. 82:5109-14.
Chronic Fatigue Syndrome
Jason LA, Unger ER, Dimitrakoff JD, Fagin AP, Houghton M, Cook DB, Marshall GD Jr, Klimas N, Snell C. (2012) Minimum data elements for research reports on CFS. Brain Behav. Immun. 26:401-6.
Steffen I, Tyrrell DL, Stein E, Montalvo L, Lee TH, Zhou Y, Lu K, Switzer WM, Tang S, Jia H, Hockman D, Santer DM, Logan M, Landi A, Law J, Houghton M, Simmons G. (2011) No evidence for XMRV nucleic acids, infectious virus or anti-XMRV antibodies in Canadian patients with chronic fatigue syndrome. PLoS One. 6:e27870.