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Maya Shmulevitz

MMI Faculty

 

Maya Shmulevitz

Maya

Department of Medical Microbiology & Immunology
University of Alberta
Department of Medicine & Dentistry
6-21 Heritage Medical Research Centre
Edmonton, Alberta T6G 2S2 
Canada

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


Web
: http://shmulevitzlab.weebly.com/index.html


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. At the same time, viruses evolve extravagant strategies to exploit the host's resources. But how do viral genes and cellular events that vary among virus variants and specific cell types contribute to whether a cell can support efficient virus replication?

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). Using both modern and traditional molecular virology techniques, research in our laboratory is focused on understanding how specific viral and host factors can promote the efficiency of virus replication in cancer cells.

Projects in the lab include:

1. Exploring 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 virus replication in cancer cells. We first select reovirus variants exhibiting improved replication on cancer cells relative to wild-type reovirus (J. Virology 2012, 86:7403). 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. Exploring 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:

  • Kevin James (Graduate Student)
  • Adil Mohamed (Graduate Student)
  • Wan Kong Yip (Graduate Student)
  • Dr. Heather Eaton (PDF)

Publications:

Click here for most recent publications