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Li Ka Shing Institute of Virology

Dr. Michael Houghton’s HCV Research makes big progress

Posted by karin.fodor on September 28, 2017
Posted in News 

The latest publications from the Houghton lab:

Marawan Ahmed, Horia H. Jalily, Aravindhan Ganesan, Michael Houghton and Khaled Barakat (2017) A Comprehensive Model of the Human Nav1.5 Sodium Channel: Structural and Mechanistic Insights of Ion Permeation & Drug Blockage. Drug Design, Development and Therapy (Accpeted)

Michael Logan, John Law, Jason Alexander Ji-Xhin Wong, Darren Hockman, Amir Landi, Chao Chen, CrCrcrawfordCrawford, Kevin Crawford, Juthika Kundu, Lesley Baldwin, Janelle Johnson, Anita Dahiya, Gerald LaChance, Joseph Marcotrigiano, Mansun Law, Steven Foung, Lorne Tyrrell, and Michael Houghton (2017) Native Folding of a Recombinant gpE1/gpE2 Heterodimer Vaccine Antigen from a Precursor Protein Fused with Fc IgG. J. Virol. January 91:1 14 doi:10.1128/JVI.01552-16

N.S. Pagadala, K. Sahu, R. Bhat, K. Syed, M. Houghton and J.A. Tuszynski (2017) In silico Strategies for Designing Anti-prion Compounds, Expert Opinion on Drug Discovery, 2017 Mar;12(3):241-248. doi: 10.1080/17460441.2017.1287171. Epub 2017 Feb 2. Review. PMID: 28118747

Santer DM, Minty GE, Mohamed A, Baldwin L, Bhat R, Joyce M, Egli A, Tyrrell DLHoughton M. (2017) A novel method for detection of IFN-lambda 3 binding to cells for quantifying IFN-lambda receptor expression. J Immunol Methods. doi:10.1016/j.jim.2017.03.001.

Santer D, Baldwin L, Tyrrell DLJ, Mohamed A, Houghton M, Joyce M, Minty G, Bhat R, Egli A.  (2017) A novel method for detection of IFN-lambda 3 binding to cells for quantifying IFN-lambda receptor expression.  J Immunol Methods. 2017 Mar 5. pii: S0022-1759(17)30004-2. doi: 10.1016/j.jim.2017.03.001. [Epub ahead of print]

Sarhan M, Abdel-Hakeem M, Mason A, Tyrrell DLJ, Houghton M.  Glycogen synthase kinase 3ß inhibitors prevent hepatitis C virus release/assembly through perturbation of lipid metabolism.  Nature Scientific Reports Published Online May 31, 2017

Mohammed A. Sarhan, Mohamed S. Abdel-Hakeem, Ishwar Hossmani, Lorne Tyrrell, Andrew Mason and Michael Houghton. (2017) GSK3b inhibitors prevent HCV release/assembly through perturbation of lipid metabolism. Nature Scientific Reports in press

 

U of A researchers uncover clue to cause of dementia in HIV patients

Posted by karin.fodor on July 25, 2017
Posted in News 

U of A researchers uncover clue to cause of dementia in HIV patients

Dr. Christopher Power, Dr. Tom Hobman & Dr. Zaikun Xu

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PLOS ONE – Top 10% cited article

Posted by karin.fodor on July 7, 2017
Posted in News 

A Hepatitis C Virus (HCV) Vaccine Comprising Envelope Glycoproteins gpE1/gpE2 Derived from a Single Isolate Elicits Broad Cross-Genotype Neutralizing Antibodies in Humans

John Lok Man Law, Chao Chen, Jason Wong, Darren Hockman, Deanna M. Santer, Sharon E. Frey, Robert B. Belshe, Takaji Wakita, Jens Bukh, Christopher T. Jones, Charles M. Rice, Sergio Abrignani, D. Lorne Tyrrell, Michael Houghton

Published: March 19, 2013; Full article

Abstract
Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volunteers who were immunized with recombinant glycoproteins gpE1/gpE2 derived from a single HCV strain (HCV1 of genotype 1a). Cross neutralization was tested in Huh-7.5 human hepatoma cell cultures using infectious recombinant HCV (HCVcc) expressing structural proteins of heterologous HCV strains from all known major genotypes, 1–7. Vaccination induced significant neutralizing antibodies against heterologous HCV genotype 1a virus which represents the most common genotype in North America. Of the 16 vaccinees tested, 3 were selected on the basis of strong 1a virus neutralization for testing of broad cross-neutralizing responses. At least 1 vaccinee was shown to elicit broad cross-neutralization against all HCV genotypes. Although observed in only a minority of vaccinees, our results prove the key concept that a vaccine derived from a single strain of HCV can elicit broad cross-neutralizing antibodies against all known major genotypes of HCV and provide considerable encouragement for the further development of a human vaccine against this common, global pathogen.

Publication in Science on Poxvirus

Posted by karin.fodor on July 7, 2017
Posted in News 

How Canadian researchers reconstituted an extinct poxvirus for $100,000 using mail-order DNA

Eradicating smallpox, one of the deadliest diseases in history, took humanity decades and cost billions of dollars. Bringing the scourge back would probably take a small scientific team with little specialized knowledge half a year and cost about $100,000.

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Zika Virus paper

Posted by karin.fodor on June 7, 2017
Posted in News 

Latest Publication:

Zika virus hijacks stress granule proteins and modulates the host stress response
June 7, 2017: J. Virol. doi:10.1128/JVI.00474-17

Untitled Post

Posted by karin.fodor on March 28, 2017
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Dr. Tom Hobman receives CIHR grant to further his studies on Zika virus

professor-tom-hobman-expert-researcher-on-the-zika-virus-lo1

Tom Hobman is a professor of cell biology at the University of Alberta, as well as a Canada Research Chair. His team was recently awarded a $500,000 grant to continue its research on the Zika virus, which has become a priority for the scientific community since outbreaks in South America and Central America in 2015. Hobman spoke to Postmedia on Thursday about studying the virus and searching for its weaknesses.

professor-tom-hobman-expert-researcher-on-the-zika-virus-ha

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Dr. Lorne Babiuk wins 2016 World Agriculture Prize

Posted by karin.fodor on September 20, 2016
Posted in News 

Developing six vaccines, shepherding world-class research facility and training more than 100 graduate students earns UAlberta’s VP of research the nod.

By Michel Proulx on September 20, 2016

The University of Alberta’s vice-president of research has won a major international award for his “exceptional and significant” lifetime achievements.

Lorne Babiuk is the 2016 World Agriculture Prize Laureate, an award bestowed by the Global Confederation of Higher Education Associations for Agriculture and Life Sciences.

“This one ranks right at the top,” said Babiuk, a world-renowned virologist who has won numerous international awards for his leadership in vaccine development and research in veterinary infectious disease control, particularly diseases that spread from animals to humans.

“I’m in medicine. I’m in agriculture. These are often two solitudes and to be able to link them and get international awards—it’s very gratifying when you can make an impact that is recognized by two completely different groups,” he said.

Babiuk devoted his career to safeguarding the health of animals and people worldwide, primarily through the development of vaccines. He consistently fulfilled the promise he showed very early on in his career as a virologist when he worked on rotavirus—a devastating disease that can be fatal for calves—and devised a new technique to grow the virus and then developed a vaccine to control it.

It was the first of six vaccines Babiuk played a major role in developing over the years.

“One of the things that veterinarians or cattle producers don’t want to see is young calves dying and they can’t do anything about it. If the cattle producer in southern Alberta loses 25 per cent of his cattle, that has a huge economic impact. But then in the developing world, the 600 million smallholders—many of them women—they have four goats. If one dies, that means a child may go to bed hungry, and we know that nutrition and proteins specifically influences cognitive development in young children. So this has an impact on their livelihood and their ability to function in the future,” explained Babiuk.

Like many other accomplished scientists around the world, Babiuk often questioned assumptions and always looked for different and better ways to find solutions to complex infectious disease issues. For example, in the early ‘80s, at a time when few people thought biotechnology would have any application in the animal health industry, he and his team of researchers developed the world’s first genetically engineered vaccine for shipping fever, a disease that was causing the North American cattle industry $1 billion a year.

A few years later, Babiuk again broke scientific ground when he espoused that understanding the fundamentals of vaccine formulation and delivery rather than antigen production was the key to increasing the efficacy of vaccines. Since then, this theory has become accepted knowledge throughout the scientific community.

Though Babiuk is a prolific researcher who has published more than 500 peer-reviewed papers and has more than 22,000 citations, he has always been committed to bringing research results into the marketplace.

That was evident while he helped build the Vaccine and Infectious Disease Organization (VIDO) at the University of Saskatchewan from 1975 onwards and led it from 1993 to 2007, building it into an international research powerhouse that, to date, has produced eight vaccines.

Babiuk’s commitment to mentoring the next generation of researchers is equally impressive. He not only supervised more than 50 PhD students and more than 50 post-doctoral fellows, but also created a unique-in-North America graduate program in vaccinology that looked as much at the ethical and social concerns arising from the production and use of vaccines in various populations as the science.

Although Babiuk has been vice-president of research at the U of A for the past nine years and will retire from the position next June, he has maintained an active research program. He’s in the middle of developing his seventh vaccine, which will protect sheep, goats and cattle from five diseases, and an eight vaccine that will protect poultry from various diseases.

“There is so much to do. You can’t rest on your laurels,” said Babiuk.

2016 Clinical Lasker Award

Posted by karin.fodor on September 20, 2016
Posted in News 

Congratulations to the winners of this year’s Clinical Lasker Award:

Charlie Rice of Rockefeller University,

Ralf Bartenschlager of the University of Heidelberg

and Michael Sofia of Arbutus Biopharma.

 

CIHR money for Zika virus research

Posted by karin.fodor on August 5, 2016
Posted in News 

 

Dr. Tom Hobman in the Department of Cell Biology has received a 5 year grant from the CIHR Project scheme:

“Zika virus biology, diagnostics and therapeutic approaches”
Value: $1,020,609
This grant allows to continue our work on Zika virus which was initially supported by seed funding from LKSIoV for emerging priorities.

Hepatitis C “time bomb” threatens many Canadians

Posted by karin.fodor on August 2, 2016
Posted in News 

 

Article in the Edmonton Journal on August 8, 2016 relating to World Hepatitis Day on July 28, 2016:

Opinion: Canada's hepatitis C screening policies are failing everyone, especially baby boomers

Dr. Lorne Tyrrell, shown in a 2015 photo, writes in a guest column with Dr. Michael Houghton that Canada needs to take prompt action to test vastly more Canadians for hepatitis C.

At this very moment, an estimated 250,000 Canadians carry a “hidden time bomb,” the hepatitis C virus, or HCV, which attacks the liver and greatly increases the risk of cirrhosis, liver cancer, liver transplants and even death.

Perhaps more alarming — and damning for Canada’s public health agency — is that 60 per cent of Canadians infected with HCV remain undiagnosed for years and even decades until showing the first symptoms of liver disease. This not only jeopardizes the health of Canadians, but also places an undue cost burden on the health-care system. In Alberta alone, 40 per cent of liver transplants are related to end-stage liver disease associated with HCV infection.

With World Hepatitis Day last week on July 28, it is distressingly obvious that far too many Canadians lack basic knowledge about hepatitis C, a disease spread largely through blood contact and intravenous drug use. Canada did not start screening our blood supply for the virus until 1992, a full three years after the hepatitis C virus was discovered. As a result, tens of thousands of Canadians were infected through blood transfusions, with baby boomers born between 1945 and 1975 among those at greatest risk.

According to a recent survey by the Canadian Liver Foundation, 80 per cent of Canadians in this age bracket are unaware of their increased risk of infection, and only 25 per cent have been tested. From a public health perspective, this level of ignorance is beyond worrisome and speaks to an urgent need for Canada to take stronger action.

In contrast, the United States became the first country in the world to recommend HCV blood screening specifically for baby boomers. Other countries such as the United Kingdom, Saudi Arabia, Belgium, France, Germany and Australia have either screening programs or screening guidelines.

The Public Health Agency of Canada has yet to follow suit with screening recommendations, for boomers or otherwise. Ontario and Prince Edward Island both of which have screening programs, the Northwest Territories has recommended one-time HCV testing for boomers and provinces such as Alberta are evaluating the effectiveness of screening.

Dr. Michael Houghton in a 2013 photo.
Dr. Michael Houghton in a 2013 photo. Shaughn Butts / Edmonton Journal

The real tragedy is that hepatitis C should stand among our greatest medical and scientific triumphs. Since the virus was discovered in 1989, research advances have led to antiviral treatments capable of curing more than 95 per cent of patients. Parallel to this, our own work continues at the University of Alberta to develop the world’s first vaccine against all seven major genotypes of the hepatitis C virus, with phase one clinical trials expected to begin next year.

Yet all the scientific advances in the world cannot make up for the absence of a concrete national strategy with a core emphasis on education, prevention, and timely and affordable access to treatment. On this front, Canada and most of our provinces are spinning their wheels. Even when patients are diagnosed, often only the sickest with advanced inflammation of the liver receive treatment fully covered by provincial pharmacare, which isn’t the case in other countries, including Australia.

The risk from inaction puts lives at risk, and ends up costing Canadians far more in the long run. A recent study published in the Canadian Journal of Gastroenterology and Hepatology showed the rates of hepatitis C in Canada are decreasing, however the prevalence of advanced liver disease is rising as the population ages. Unless we take action, we can expect 32,460 individuals infected with HCV will die from liver complications by 2035 and the total health-care costs associated with chronic HCV will rise by 60 per cent.

Here in Alberta, a recent analysis prepared for Alberta Health estimates that screening boomers and the general population represents “good value for money” in terms of quality-adjusted life years, a measure of disease burden. Screening and treating the entire HCV-infected population in this province would cost $253 million; screening and treating just boomers is estimated at $134 million and represents a reasonable place to start.

These costs are indeed high, but pale in comparison with what’s at stake.

Michael Houghton is a professor and Canada Excellence Research Chair in Virology at the University of Alberta and led the team that discovered the hepatitis C virus. Lorne Tyrrell is a distinguished university professor of medicine and director of the Li Ka Shing Institute of Virology at the University of Alberta. He co-developed the world’s first oral antiviral treatment for hepatitis B.