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Senior Scientist, Cancer Therapeutics, Ottawa Hospital Research Institute
Professor, Depts. of Medicine and Biochemistry, Microbiology & Immunology
University of Ottawa
Key Words: oncolytic virus, protein translation, cancer, therapeutics
Research Interests
Oncolytic Viruses: Novel Cancer Therapeutics
Current cancer therapies often have limited efficacy and high toxicity and thus novel approaches to treatment are sought. Viruses have many characteristics which make them desirable as a therapeutic strategy for the treatment of cancer including their ability to infect cells and replicate, induce cell death, release viral particles and spread through human tissues. We have shown that a variety of viruses selectively replicate in and kill human cancer cell lines, primary patient samples and purge contaminated bone marrow of leukemic cells. Although the mechanisms of preferential oncolytic activity are not yet completely understood, our hypothesis is that during tumor evolution, genetic abnormalities accumulate that, while providing malignancies a growth/survival advantage, also compromise the antiviral program of tumour cells. One cytokine pathway that seems to be frequently defective in tumour cell lines is the interferon signaling cascade. In particular, mutants of Vesicular Stomatitis Virus which strongly induce interferon expression are safe anti-cancer therapeutics in a variety of animal tumour models. The Bell lab is optimizing and selecting for VSV strains with improved efficacy. We are also testing the role of the immune system in both the enhancement and inhibition of oncolytic virus activity. Other virus strains are also being tested for oncolytic activity.
A second major thrust in the Bell lab is the understanding of how protein translation is controlled under a variety of stress situations and in cancer cells. One long term goal of this project is to identify mRNA sequences that are involved in regulating protein synthesis and using this information for the development of novel anti-cancer strategies.
Most Recent Publications (provided by The Ottawa Hospital Library Database)
Alain T;Lun X;Martineau Y;Sean P;Pulendran B;Petroulakis E;Zemp FJ;Lemay CG;Roy D;Bell JC;Thomas G;Kozma SC;Forsyth PA;Costa-Mattioli M;Sonenberg N;, (2010 Jan 4), Vesicular stomatitis virus oncolysis is potentiated by impairing mTORC1-dependent type I IFN production, Proc Natl Acad Sci U S A, -> view abstract
Guse K;Sloniecka M;Diaconu I;Ottolino-Perry K;Tang N;Ng C;Le BF;Bell JC;McCart JA;Ristimaki A;Pesonen S;Cerullo V;Hemminki A;, (2010 Jan), Antiangiogenic arming of an oncolytic vaccinia virus enhances antitumor efficacy in renal cell cancer models, J Virol , Vol.84, Issue 2, 856-866 -> view abstract
Ottolino-Perry K;Diallo JS;Lichty BD;Bell JC;Andrea MJ;, (2010 Feb), Intelligent design: combination therapy with oncolytic viruses, Mol Ther, Vol.18, Issue 2, 251-263 -> view abstract
Heikkila JE;Vaha-Koskela MJ;Ruotsalainen JJ;Martikainen MW;Stanford MM;McCart JA;Bell JC;Hinkkanen AE;, (2010), Intravenously administered alphavirus vector VA7 eradicates orthotopic human glioma xenografts in nude mice, PLoS One, Vol.5, Issue 1, e8603 -> view abstract
Brown CW;Stephenson KB;Hanson S;Kucharczyk M;Duncan R;Bell JC;Lichty BD;, (2009 Jan), The p14 FAST protein of reptilian reovirus increases vesicular stomatitis virus neuropathogenesis, Journal of Virology, Vol.83, Issue 2, 552-561 -> view abstract
Zhang KX;Matsui Y;Hadaschik BA;Lee C;Jia W;Bell JC;Fazli L;So AI;Rennie PS;, (2009 Dec 2), Down-regulation of type I interferon receptor sensitizes bladder cancer cells to vesicular stomatitis virus-induced cell death, Int J Cancer, -> view abstract
Lun XQ;Jang JH;Tang N;Deng H;Head R;Bell JC;Stojdl DF;Nutt CL;Senger DL;Forsyth PA;McCart JA;, (2009 Apr 15), Efficacy of systemically administered oncolytic vaccinia virotherapy for malignant gliomas is enhanced by combination therapy with rapamycin or cyclophosphamide, Clin Cancer Res, Vol.15, Issue 8, 2777-2788 -> view abstract
Parato KA;Lichty BD;Bell JC;, (2009), Diplomatic immunity: Turning a foe into an ally, Current Opinion in Molecular Therapeutics, Vol.11, Issue 1, 13-21 -> view abstract
Nguyen TL;Abdelbary H;Arguello M;Breitbach C;Leveille S;Diallo JS;Yasmeen A;Bismar TA;Kirn D;Falls T;Snoulten VE;Vanderhyden BC;Werier J;Atkins H;Vaha-Koskela MJ;Stojdl DF;Bell JC;Hiscott J;, (2008 Sep 24), Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis, Proc Natl Acad Sci U S A, Vol.105, Issue 39, 14981-14986 -> view abstract
Liu TC;Hwang TH;Bell JC;Kirn DH;, (2008 Sep), Development of targeted oncolytic virotherapeutics through translational research. [Review] [87 refs], Expert Opinion on Biological Therapy, Vol.8, Issue 9, 1381-1391 -> view abstract
Note: This is not a complete list of publications. More publications may be available in The Ottawa Hospital Library database and Pubmed (search by last name and initials).
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