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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)
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
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
Hadaschik BA;Zhang K;So AI;Bell JC;Thuroff JW;Rennie PS;Gleave ME;, (2008 Sep), [Oncolytic vesicular stomatitis viruses as intravesical agents against non-muscle-invasive bladder cancer]. [German], Urologe (Ausg, Issue 9, 1145-1151 -> 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
Power AT;Bell JC;, (2008 May), Taming the Trojan horse: optimizing dynamic carrier cell/oncolytic virus systems for cancer biotherapy, Gene Ther, Vol.15, Issue 10, 772-779 -> view abstract
Colina R;Costa-Mattioli M;Dowling RJ;Jaramillo M;Tai LH;Breitbach CJ;Martineau Y;Larsson O;Rong L;Svitkin YV;Makrigiannis AP;Bell JC;Sonenberg N;, (2008 Mar 20), Translational control of the innate immune response through IRF-7, Nature, Vol.452, Issue 7185, 323-328 -> view abstract
Maire G;Brown CW;Bayani J;Pereira C;Gravel DH;Bell JC;Zielenska M;Squire JA;, (2008 Mar), Complex rearrangement of chromosomes 19, 21, and 22 in Ewing sarcoma involving a novel reciprocal inversion-insertion mechanism of EWS-ERG fusion gene formation: a case analysis and literature review. [Review] [50 refs], Cancer Genetics & Cytogenetics, Vol.181, Issue 2, 81-92 -> view abstract
Hadaschik BA;Zhang K;So AI;Fazli L;Jia W;Bell JC;Gleave ME;Rennie PS;, (2008 Jun 15), Oncolytic vesicular stomatitis viruses are potent agents for intravesical treatment of high-risk bladder cancer, Cancer Research, Vol.68, Issue 12, 4506-4510 -> view abstract
Park BH;Hwang T;Liu TC;Sze DY;Kim JS;Kwon HC;Oh SY;Han SY;Yoon JH;Hong SH;Moon A;Speth K;Park C;Ahn YJ;Daneshmand M;Rhee BG;Pinedo HM;Bell JC;Kirn DH;, (2008 Jun), Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial, Lancet Oncol, Vol.9, Issue 6, 533-542 -> 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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