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
Canada

Ph : (780) 248-1888
Fx : (780) 492-7521
Em: michael.houghton@ualberta.ca

Positions:

• Canada Excellence in Research Chair
• Professor, Dept. of Medical Microbiology & Immunology

Research:

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.

People:

• Dr. Deanna Santer (PDF)
• Dr. Amir Landi (PDF)
• Dr. Max Rosario (PDF)
• Dr. Mike Logan (Research Associate)
• Dr. John Law (Research Associate)
• Dr. Rakesh Bhat (Research Associate)
• Jason Wong (MSc Student)
• Darren Hockman (Lab Manager)
• Chao Chen (Technician)
• David Beyer (Technician)
  

I am looking for people to join my lab. See here.

Publications:

Click here for most recent publications

Selected Publications:

Houghton M. The long and winding road leading to the identification of the hepatitis C virus. J Hepatol. 2009 Nov;51(5):939-48. Epub 2009 Sep 10. Review.

Drane D, Maraskovsky E, Gibson R, Mitchell S, Barnden M, Moskwa A, Shaw D, Gervase B, Coates S, Houghton M, Basser Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX vaccine: a phase I study in healthy volunteers. R. Hum Vaccin. 2009 Mar;5(3):151-7. Epub 2009 Mar 15

Lin Y, Kwon T, Polo J, Zhu YF, Coates S, Crawford K, Dong C, Wininger M, Hall J, Selby M, CoitD, Medina-Selby A, McCoin C, Ng P, Drane D, Chien D, Han J, Vajdy M, Houghton M. 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. 2008 Aug;82(15):7492-503. Epub 2008 May 28.

Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M. The way forward in HCV treatment—finding the right path. Nat Rev Drug Discov. 2007 Dec;6(12):991-1000. Review.Erratum in: Nat Rev Drug Discov. 2008 Jan;7(1):102. Nat Rev Drug Discov. 2008 May;7(5):458.

Stamataki Z, Coates S, Evans MJ, Wininger M, Crawford K, Dong C, Fong YL, Chien D, Abrignani S, Balfe P, Rice CM, McKeating JA, Houghton M. Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies. Vaccine. 2007 Nov 7;25(45):7773-84. Epub 2007 Sep 14.

Vajdy M, Selby M, Medina-Selby A, Coit D, Hall J, Tandeske L, Chien D, Hu C, Rosa D, Singh M, Kazzaz J, Nguyen S, Coates S, Ng P, Abrignani S, Lin Y-L, Houghton M, O’Hagan D. Hepatitis C virus polyprotein vaccine formulations capable of inducing broad antibody and cellular immune responses ( 2006) J Gen Virol, 87,225

Houghton M, Abrignani S. Prospects for a vaccine against the hepatitis C virus. (2005) Nature, 436, 961.

O'Hagan DT, Singh M, Dong C, Ugozzoli M, Berger K, Glazer E, Selby M, Wininger M, Ng P, Crawford K, Paliard X, Coates S, Houghton M. Cationic microparticles are a potent delivery system for a HCV DNA vaccine. (2004) Vaccine, 23, 672.