Dr. Maya Shmulevitz

Assistant professor, Department of Medical Microbiology and Immunology Canada Research Chair in Molecular Virology and Oncotherapy University of Alberta
Researcher of the month: 
Dec 2012

Tinkering with natural cancer killers

“To this day, I am fascinated by viruses,” says Dr. Maya Shmulevitz, a recently minted Canada Research Chair in Molecular Virology and Oncotherapy at the University of Alberta (Edmonton).

When zombie fans invited her to talk at a showing of 28 days later, Shmulevitz spoke about the beautiful simplicity yet complex nature of viruses. Rabies, for example, “has only five proteins, yet it’s up against a host with 25,000 genes,” she explains.

“The science of how viruses evolve unique strategies to overcome hurdles amazes me. Only a few proteins allow a virus to enter a cell, replicate, leave, and spread to infect other cells. Viruses are simple yet complex enough to be very specific. For example, HIV doesn’t behave like influenza.” 

Natural cancer killers

Several viruses, incapable of replicating in normal cells, replicate specifically in cancer cells. They successfully kill host cancer cells as part of their natural cycle. Such oncolytic (cancer-killing) viruses have attracted the attention of scientists like Shmulevitz, who are exploring their potential to become effective cancer therapies.

Shmulevitz’s goal is to supercharge these viruses at the molecular level to become predictable, potent cancer killers. She firmly believes that, within 20 years, oncolytic viruses will become viable anti-cancer treatments.

At the Shmulevitz lab, she and her U of A research team are studying oncolytic viruses to find answers to fundamental questions. Why do they replicate in cancer cells better than normal cells? Why are some cancer cells more susceptible to them than others? What specific factors in the virus and host promote this cancer-killing ability?

Tweaking reovirus

To forward her understanding, Shmulevitz has worked with a lowly virus called reovirus. This stable virus has co-existed with humans for centuries. It is typically found in the intestines. Why study it? Reovirus has an unusual ability.

“The interesting thing about reovirus is that it replicates better in cancer cells than normal cells,” she explains. “But only 1% of viral particles ever get going in cancer cells; 99% can’t do anything. That’s a huge wasted potential. We can make small changes in the virus to drastically affect that number.”

Working with mentor Dr. Patrick Lee at Dalhousie University, Shmulevitz used natural selection to enhance the natural ability of reovirus to kill cancer cells.

“Small changes to a viral protein can have a large effect on how well a virus replicates in cancer cells,” she says. “We kept picking the viruses that did very well in cancer cells, then screened them to make sure they still couldn’t replicate well in normal cells. Then, we wanted to know what did it take? So we sequenced the virus to find out what changes increased its infectivity in cancer cells.”

At the U of A, Shmulevitz and her research team continue to study the mechanisms that evolved during these experiments. If they can identify why it kills better, they hope to learn how to fine-tune other oncolytic viruses to achieve the same benefits.

“We know that there were changes in the virus that made it better at killing cancer cells. The idea is, if we can understand how those changes promote that ability, we can come back at it and make that change even stronger.”

They have found that changes in structure – in how reovirus is put together – have enhanced its oncolytic potency.

Calgary-based Oncolytics Biotech® is currently testing a proprietary variant of reovirus (Reolysin®) as an anti-cancer therapy for head and neck cancer in Phase 3 trials.

Unmasking cancer

An oncolytic virus works two ways. On its own, it invades, replicates inside, and explodes (lyses) cancer cells from within to be released to infect again. Research at other laboratories has shown that oncolytic viruses also help to unmask cancer, which is notoriously good at hiding from the immune system.

It’s a double whammy, Shmulevitz explains. “The immune system goes after the virus, but the virus is inside the cancer cell, so it kills the cancer cell. By killing cancer cells in the presence of a whole bunch of immune cells, the virus shows the immune system what the cancer cells look like.”

The immune system then produces antigen to fight cancer, alongside the oncolytic virus. Eventually, it attacks and rids the body of the oncolytic virus as well.

Alberta-grown career

Shmulevitz’s career was nurtured at the University of Alberta. During summers as an undergraduate biochemistry student, she worked at the U of A’s world-class virology labs under Dr. Lorne Tyrell, where she studied a polio-like virus and hepatitis B.

“The university had a strong foundation in virology back then. Today, it’s really quite impressive,” she says. “In biochemistry, you learn about proteins and how they fold. When you learn about viruses, you can apply that knowledge.”

She journeyed to the Weizmann Institute in Israel, then the Argonne National Laboratories in Chicago to work as a research assistant on the Human Genome Project, during the era when scientists raced to complete our genetic map. During efforts to sequence the genome faster, Shmulevitz helped to discover and learned to apply new molecular technologies.

She returned to Canada to continue her studies in virology as a graduate student at Dalhousie University and in Saskatoon at the Vaccine and Infectious Disease Organization. As a postdoctoral fellow under Dr. Patrick Lee at Dalhousie, she became excited about the prospect of applying her knowledge of viruses to the fight against cancer. 

“The more you learn,” she says, “the more you can it put all together.”