Lyman Duff Medical Building, McGill University
3775 University St.,
Montreal, QC H3A 2B4
greg.matlashewski [at] mcgill.ca (Email)
Interview in the Reporter: Pummelling parasites
Human papillomavirus and cervical cancer
Human papillomaviruses (HPV) are the major etiological agents for the development of cervical cancer. Cervical cancer is the second most common form of cancer among women on a world-wide basis. We have previously identified several oncogenes within the genome of HPV and our focus is now to define how these viral oncogenes are involved in malignant transformation.
Our current emphasis is on the HPV E6 oncogene product which is capable of binding to and inactivating the cellular tumour suppressor protein p53. My laboratory is currently defining the biochemical and biological consequences of the E6/p53 interaction.
We are also studying how a polymorphism in the p53 gene may predispose women to HPV associated cervical cancer. Defining the molecular basis for viral oncogenesis in this manner may define strategies for disrupting viral transforming activities and will provide information on malignant transformation in general.
My laboratory is also involved in basic research to define the involvement of p53 in cell programed death and how this may be applied toward the development of new anticancer treatments.
Human Leishmania infection
Leishmania is a protozoan which is transmitted to humans by the sandfly vector and causes leishmaniasis which is often fatal, particularly in children of developing countries. Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization.
We are currently cloning and characterizing virulence genes from Leishmania. In this manner, we are attempting to define novel targets for treatment of this infection. Attempts are underway to develop a live attenuated vaccine for this infection using gene targeting to delete virulence genes from the Leishmania genome.
Studies are also underway to test various macrophage activating compounds as potential chemotherapeutic compounds against leishmaniasis. Towards this goal, we are now beginning a WHO supported human clinical trial in Peru.
Selected Recent Publications
Zhang WW, Chan KF, Song Z, Matlashewski G.
Expression of a Leishmaniadonovani nucleotide sugar transporter in Leishmaniamajor enhances survival in visceral organs. Exp Parasitol. 2011 Dec;129(4):337-45. Epub 2011 Sep 29.
Gosline SJ, Nascimento M, McCall LI, Zilberstein D, Thomas DY, Matlashewski G, Hallett M.
Intracellular eukaryotic parasites have a distinct unfolded protein response. PLoS One. 2011 Apr 29;6(4):e19118.
Yam KK, Hugentobler F, Pouliot P, Stern AM, Lalande JD, Matlashewski G, Olivier M, Cousineau B.
Generation and evaluation of A2-expressing Lactococcus lactis live vaccines against Leishmania donovani in BALB/c mice. J Med Microbiol. 2011 Sep;60(Pt 9):1248-60. Epub 2011 Apr 28.
Matlashewski G, Arana B, Kroeger A, Battacharya S, Sundar S, Das P, Sinha PK, Rijal S, Mondal D, Zilberstein D, Alvar J.
Visceral leishmaniasis: elimination with existing interventions. Lancet Infect Dis. 2011 Apr;11(4):322-5. Review.
Thomas M, Kranjec C, Nagasaka K, Matlashewski G, Banks L.
Analysis of the PDZ binding specificities of Influenza A virus NS1 proteins. Virol J. 2011 Jan 19;8:25.
Zhang WW, Matlashewski G.
Screening Leishmania donovani-specific genes required for visceral infection. Mol Microbiol. 2010 Jul;77(2):505-17. Epub 2010 Jun 1.
McCall LI, Matlashewski G.
Localization and induction of the A2 virulence factor in Leishmania: evidence that A2 is a stress response protein. Mol Microbiol. 2010 Jul;77(2):518-30. Epub 2010 May 24.