The work of internationally recognized virologists in the Faculty of Medicine & Dentistry has propelled the University of Alberta to the front lines of a biological war as old as life on earth.
For more than two billion years, viruses have found ways to invade cells in a host organism and replicate by hijacking the cells’ machinery. Cells have fought back over time by developing complex immune responses that are triggered when their walls have been breached. But viruses develop counter strategies to evade these defenses or suppress them. Viruses may be the simplest life forms on the planet but we humans often find ourselves on the losing end of this ongoing battle despite our complexity. They remain one of the most significant global health threats. The World Health Organization says nearly one-third of preventable deaths are from infections, most of them viral.
The WHO estimates that more than 500 million (one in 12) people worldwide are chronically infected with hepatitis B or hepatitis C, the most common causes of fatal liver cancer. And while vaccines have given us the upper hand on viruses such as polio, smallpox and yellow fever, deadly new ones such as HIV, SARS and avian flu have emerged in recent times. Influenza viruses keep a step ahead of makers of vaccines and antiviral drugs by mutating. It’s no wonder that Kennedy Shortridge, discoverer of H5N1 (avian flu) in Asia, described viruses as “tiny terrorists (that) travel light, switch identity easily and pursue their goals with deadly determination.”
The “holy grail” of virus research would be new classes of drugs that viruses cannot develop resistance against, and ideally, drugs that would work against many different viruses, including new ones as they arise. The University of Alberta has been assembling the personnel, infrastructure and strategies needed to pursue these ambitious goals along with the world’s best. As one of the leading centres for virology in Canada, the U of A also continues to be dedicated to the study of how viruses infect cells and cause disease, and how virus infections can be prevented with vaccines.
Highly respected researchers in the Faculty of Medicine & Dentistry at the University of Alberta have been investigating a number of viruses and the body’s immune response to infection. They hold numerous grants, have published extensively and are cited often by their peers. Here are some of them:
Lorne Tyrrell, MD, PhD, one of Canada’s most distinguished medical scientists and the director of the new Li Ka Shing Institute of Virology, developed the first treatment for hepatitis B, a drug called lamivudine now being used in more than 200 countries. He continues to work on hep B therapies and is also focusing on a vaccine that would prevent hepatitis C.
Michael Houghton’s laboratory works on hepatitis C vaccines and hepatitis B immunotherapies as well as investigating potential infectious etiologies of other human inflammatory diseases.
Babita Agrawal, PhD, works in the area of T-cell responses and their regulation in context of hepatitis C virus infection, cancer and autoimmune diseases. In addition she and her team are currently working on novel about immunomodulatory agents for use in autoimmune diseases and transplantation.
Lorne Babiuk, PhD, vice-president of research, is a virologist and internationally known for his advanced work on enhancing the effectiveness of vaccines. He brings important links with other virology centres in Western Canada, including the Vaccine & Infectious Diseases Organization in Saskatoon (which he led prior to his current U of A post).
Chris Bleackley, PhD, is focusing on understanding how cytotoxic T-cells kill their targets. T-lymphocytes play a key role in the body’s defences against disease and are important effectors in organ transplant rejection. Knowledge of how they function may lead to the development of new forms of rational immunotherapy.
Deborah Burshtyn, PhD, is investigating the collaboration between various “killer cell Ig-like receptors” or KIRs and a related receptor LIR1. The expression pattern LIR1 on natural killer cells varies widely from person to person, so Burshtyn and her team are currently investigating the basis of this diversity with a view to determining implications for susceptibility and resistance to infectious diseases, autoimmunity and cancer.
The more we can learn about the cellular systems that viruses depend upon, and virus survival mechanisms, the closer we will be to finding new and better ways to stop them. David Evans, PhD, and Michele Barry, PhD, are focusing on poxviruses. Barry, a Howard Hughes scholar, is a recognized leader in molecular virology and host/virus interactions. One immune response of cells when they are invaded is to “kill themselves,” thus preventing the virus from spreading. Barry is studying how the poxvirus suppresses this defensive response in the host cell. Evans is an expert in how similar strains of virus swap bits of their genetic material during virus growth and recombine it to create new viruses. In the past few years he has expanded his work into an area called oncolytic virology. Scientists in this field are exploring the use of viruses to kill cancer cells. Evans is experimenting with modified poxviruses that would target tumours and leave normal cells alone.
Edan Foley, PhD, is researching immune signalling, RNA interference and genomics. He is using cell and molecular biology tools and genetic techniques to decipher critical innate immune responses in the fruit fly ordrosophila melanogaster.
Philip Halloran, MD, PhD, is director of the Alberta Transplant Applied Genomics Centre. He has worked extensively on the regulation of gene expression in transplant organs undergoing rejection, the effect of tissue injury in transplant organs and age effects.
Mary Hitt, PhD, is also involved in oncolytic work. She is studying the use of adenoviruses (which normally cause harmless respiratory infections) as a weapon against cancer cells.
Tom Hobman, PhD, is an authority on host-virus interactions in cells infected with rubella and West Nile viruses. He wrote the chapter on rubella in a widely used textbook on viruses.
Viruses cause serious problems for post-transplant patients who must often suppress their immune systems with anti-rejection drugs for the rest of their lives, and for cancer patients undergoing chemo or radiation therapy. These patients are especially vulnerable to influenza and flare-ups of latent herpes viruses. Atul Humar, MD, and Deepali Kumar, MD, are conducting basic, translational and clinical research in this area.
Understanding the biological functions of proteins, especially those of enzymes, is where Michael James’ expertise lies. What preoccupies him is the orderly arrangement of atoms within enzymes and proteins. A pioneer in the field of protein crystallography, James, PhD, established the first Canadian laboratory devoted to that pursuit at the U of A in 1968.
The main research focus for Kevin Kane, PhD, is to understand how CTL and natural killer—or NK—cells recognize tumour cells or virally infected cells and destroy them. Kane also looks at how some tumour cells and virally infected cells manage to evade and/or resist the recognition and actions of killer cells.
Katharine Magor, PhD, says ducks are the primary host of influenza virus. Magor’s research looks at understanding how the duck successfully clears the virus, which may identify new strategies to prime our immune defences.
Andy Mason, MD, is working with Gane Wong, PhD, (iCORE Chair in Bioinformatics) and doing important discovery work on retroviruses (HIV falls into this group). Retroviruses are especially problematic since they leave behind part of their genetic material in the chromosomes of infected people. So far there is no way to eliminate this type of virus from the body; it must be constantly suppressed with antiviral drugs or it will start replicating again. Nobel laureate Peter Medawar described viruses as “a piece of bad news wrapped in a protein.” This is especially true of retroviruses.
Hanne Ostergaard, PhD, is interested in understanding how cytotoxic T lymphocytes (T cells)—called CTL—become activated to kill. CTL are essential for the elimination of viral infections and infections by a number of other intracellular pathogens. CTL are also likely to play a role in the elimination of cancer and as such are the targets for a number of different cancer vaccine strategies.
Xiaoli Lilly Pang, MD, PhD, is pursuing research into the causes of viral gastroenteritis. She is using highly sensitive molecular diagnostic technologies for the detection and identification of viruses associated with these and other clinical disorders.
Chris Power, MD, has a worldwide reputation as an expert in how HIV/AIDS, West Nile and other viruses affect the central nervous system. His work is helping to provide insights into how long-term HIV infections can contribute to dementia.
Jutta Preiksaitis, MD, has been doing research relating to infectious disease since 1983, particularly in the areas of epidemiology, pathogenesis, and diagnosis of infections transmitted by organ transplantation and blood transfusion.
Research in the lab of Linda Reha-Krantz, PhD, is directed at determining how DNA polymerases copy DNA with high fidelity. Reha-Krantz says it is important to understand the mechanism of DNA replication because aberrant replication can result in mutations that contribute to the development of human diseases such as cancer and to aging.
Joan Robinson, PhD, is the director of the Pediatric Infectious Diseases Residency Training Program. She is also a professor of pediatrics at the U of A and does research in pediatric infectious diseases and respiratory viruses.
Luis Schang, PhD, is interested in the roles that cellular proteins and lipids play in infection, replication and pathogenesis of viruses and prions, with the ultimate goal of finding novel antiviral drugs.
Maya Shmulevitz, PhD, is exploring ways to supercharge the cancer killing activity of promising oncolytic viruses such as reovirus. Her laboratory discovers new reovirus variants with improved oncolytic potency, and examines how specific virus mutations promote replication in cancer cells.
James Smiley, PhD, studies virus-host interactions and is an internationally recognized expert on herpes viruses. These include herpes 1 and 2, chickenpox, shingles and Epstein-Barr virus (EBV causes mononucleosis and also causes some cancers). People infected with a herpes virus are infected for life; the virus “goes underground,” biding its time in a dormant form and flaring up when immune defences become weak. Smiley has made groundbreaking discoveries about how some of these viruses regulate their own growth and suppress elements of the cell’s antiviral defences.