Robert Bristow

Robert Bristow, MD, PhD, FRCPC

Dr. Bristow is a Clinician-Scientist at the Ontario Cancer Institute/Princess Margaret Hospital and Professor within the Departments of Radiation Oncology and Medical Biophysics at the University of Toronto. He received his MD, PhD from the University of Toronto (1992; 1997) with post-graduate training at the MD Anderson Cancer Center, Massachusetts General Hospital and Erasmus University-Rotterdam. His laboratory has shown that the tumour microenvironment alters DNA repair which may be Achille’s heel in resistant cancer cells. He is currently developing novel genomic signatures relating to DNA repair and prostate cancer to predict treatment response. Dr Bristow is currently Co-Director of the STTARR Innovation Imaging Facility (MaRS Complex) and is Lead for the Canadian Prostate Cancer Genome Sequencing Project (CPC-GENE); part of the International Cancer Genome Consortium (ICGC). 
DNA Repair and Novel Therapeutics in Solid Tumours

Cells have developed a sophisticated approach to the initial sensing and subsequent repair of DNA damage to preserve genetic stability. The objective of my clinico-translational laboratory is to understand the effect of the tumour microenvironment on the ATM-p53-53BP1 DNA damage signaling pathway and DNA double-strand break (DNA-dsb) repair. Our studies suggest that hypoxic tumour cells can have decreased DNA-dsb repair (e.g., decreased homologous recombination) and an aggressive ''mutator'' phenotype. We are therefore tracking DNA damage responses and repair within normal and tumour tissues to develop novel diagnostics and molecular-targeted therapies.

We interrogate protein-protein interactions during DNA-dsb repair and cell-cycle checkpoints using: siRNA knockdowns, DNA-rejoining assays (comet and CFGE assays), chromatin immunoprecipitation (ChIP), biochemical fractionation, fluorescently-tagged proteins and quantitative confocal microscopy with UV-microbeams (www.sttarr.ca).
 

  1. Cancer therapy and DNA repair: Mutations in DNA repair and tumour suppressor genes are common in many human cancers. We are interested in certain mutated DNA damage proteins (i.e., MTp53, ATM, 53BP1) and DNA damage cell cycle checkpoints. This can lead to therapy resistance. We are tracking the sub-cellular location and function of ATM-dependent protein phosphoforms in response to DNA breaks and evaluating new therapies that target MTp53.

  2. Hypoxia, DNA repair and prostate cancer: Many prostate cancer patients die each year solely from the failure of radical radiotherapy to control the primary tumour. We are interested in developing genomic (SNP, CGH) and proteomic (serum, plasma or urine) biomarkers to predict cancer therapy cure and toxicity. This includes the assessment of tissue microarrays (TMAs) for novel protein expression in patients who fail therapy. For example, we are investigating the role of hypoxia as a negative prognostic factor in prostate and other cancers. We believe that novel cancer therapies can target these resistant hypoxic cells by taking advantage of DNA repair defects. We therefore hope to select the most effective treatment for individual patients based on individual biology. For more information, vist the UHN Radiation Medicine Program website. 
Nat Genet. 2016 Aug 15;
Guo H, Ahmed M, Zhang F, Yao CQ, Li S, Liang Y, Hua J, Soares F, Sun Y, Langstein J, Li Y, Poon C, Bailey SD, Desai K, Fei T, Li Q, Sendorek DH, Fraser M, Prensner JR, Pugh TJ, Pomerantz M, Bristow RG, Lupien M, Feng FY, Boutros PC, Freedman ML, Walsh...
BMC Bioinformatics. 2016;17:305
Masella AP, Lalansingh CM, Sivasundaram P, Fraser M, Bristow RG, Boutros PC
Oncotarget. 2016 Jul 16;
Castelo-Branco P, Leão R, Lipman T, Campbell B, Lee D, Price A, Zhang C, Heidari A, Stephens D, Boerno S, Coelho H, Gomes A, Domingos C, Apolonio JD, Schäfer G, Bristow RG, Schweiger MR, Hamilton R, Zlotta A, Figueiredo A, Klocker H, Sültmann H, Tabori U
Bl Cancer. 2016;2(1):101-109
Boström PJ, Thoms J, Sykes J, Ahmed O, Evans A, van Rhijn BW, Mirtti T, Stakhovskyi O, Laato M, Margel D, Pintilie M, Kuk C, Milosevic M, Zlotta AR, Bristow RG
Neoplasia. 2016 Jun;18(6):347-55
Tan Q, Wang M, Yu M, Zhang J, Bristow RG, Hill RP, Tannock IF
Cancer. 2016 May 24;
McPartlin AJ, Glicksman R, Pintilie M, Tsuji D, Mok G, Bayley A, Chung P, Bristow RG, Gospodarowicz MK, Catton CN, Milosevic M, Warde PR
Prostate. 2016 May 16;
Jin CS, Overchuk M, Cui L, Wilson BC, Bristow RG, Chen J, Zheng G
Can Urol Assoc J. 2016 Jan-Feb;10(1-2):25-30
Nayan M, Bhindi B, Yu JL, Mamdani M, Fleshner NE, Hermanns T, Chung P, Milosevic M, Bristow R, Warde P, Hamilton RJ, Finelli A, Jewett MA, Zlotta AR, Sridhar SS, Kulkarni GS

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