MMI Faculty

 

Maya Shmulevitz

Department of Medicial Microbiology & Immunology
University of Alberta
Department of Medicine & Dentistry
6-020 Katz Group Centre
Edmonton, Alberta T6G 2E1
Canada

Office Phone: (780) 492-0623
Fax: (780) 492-7521
Email: maya.shmulevitz@ualberta.ca

Position:

• Assistant Professor, Department of Medical Microbiology & Immunology, University of Alberta

Research:

What makes a virus infect one cell but not another? We have come to appreciate that a multitude of cellular processes (i.e. receptor expression, cytoskeletal rearrangement, nuclear import, apoptosis, etc.) can impact the replication proficiency of specific viruses. But how do these cellular events vary among specific cell types and contribute to differential susceptibility? Interestingly, several viruses specifically replicate in cancer cells, while being relatively incapable of replicating in normal cells. These oncolytic viruses are being explored as cancer therapeutics in a variety of mouse models and human trials. In addition to their therapeutic potential, oncolytic viruses provide great model systems to study determinants of host specificity and define new molecular characteristics of cancer.
Mammalian orthoreovirus 3 (reovirus) is a non-pathogenic, non-enveloped double-stranded RNA virus that inherently targets Ras-transformed cells (EMBO J. 1998, 17:3351). Research in my laboratory is focused on understanding why reovirus preferentially replicates in cancer cells. Using both ‘the latest’ and traditional molecular virology techniques, we are discovering how reovirus genes impact oncolytic potency.
Projects in the lab include:
1. Reovirus factors (i.e. genes and proteins) that promote virus replication in cancer cells. We are using reovirus variants to pinpoint viral protein mutations that promote reovirus replication on specific cancer cells. We first select reovirus variants exhibiting improved replication on cancer cells relative to wild-type reovirus. We use genetic analysis to associate specific gene mutations with enhanced reovirus oncolytic potency. Finally, through an assortment of molecular and biochemical methods, we are exploring how these viral gene mutations promote reovirus replication in cancer cells.
2. Activation mechanisms and consequences of host antiviral and stress responses to reovirus. In normal cells, reovirus infection results in activation of several signaling pathways that ultimately induce an antiviral response and restrict reovirus replication (Cancer Res 2010, 70: 4912). In Ras-transformed cells, the interferon-mediated antiviral response is impaired, therefore permitting efficient reovirus replication. The goals of this project are to define viral factors involved in activation of cell signaling following reovirus infection; discover how cell signaling differs among unique cancer and normal cell types; and pinpoint anti-viral mediators that effectively restrict reovirus infection in normal cells.
Ultimately, using new reovirus variants identified by project 1, and combination therapies suggested by project 2, we hope to optimize reovirus for improved specificity and/or potency in cancer therapy.

People:

• Adil Mohamed (Graduate Student)

Publications:

Click here for most recent publications