MENU
NEWS
RESEARCH

WORLD CLASS BASIC, TRANSLATIONAL AND CLINICAL RESEARCH

MENU
Translational Oncogenomics - Rob Bristow

Rob obtained his BSc in 1986 at the University of Toronto, where he went on to complete his Medical Degree in 1992 and later his PhD in Medical Biophysics in 1997. He has since been a Clinician-Scientist and Professor within the Departments of Radiation Oncology and Medical Biophysics at the University of Toronto. As a Senior Scientist at the Princess Margaret Cancer Centre he treated genitourinary cancers. Rob is twice a Canadian Foundation for Innovation (CFI) awardee. He was made a Canadian Cancer Society Research Scientist in 2004 and an ESTRO Honorary Fellow in 2011.

He became the Director of the Manchester Cancer Research Centre (MCRC) in August 2017 to develop a new cancer strategy and lead the continued growth of the MCRC.

Introduction

Control of genome stability requires careful coordination between cell cycle checkpoint control and DNA repair mechanisms. Defects in the repair of DNA double-stranded breaks have been associated with acquiring genetic instability, particularly in genes responsible for homologous recombination (HR) such as BRCA1 and BRCA2. Defects in these genes lead to an increased risk of ovarian and breast cancer in women and prostate cancer in men. BRCA2- associated prostate cancers have a particular poor outcome with more than 50% of men dead at 5 years after local therapy. More recently, other DNA repair gene mutations or dysfunction have been linked to aggressive prostate cancer leading to castrate resistance and the metastatic phenotype.

Our group is therefore interested in the mechanisms through which hypoxia and defects or mutations in DNA repair genes lead to prostate cancer aggression.

Publications

Hopkins JF, Sabelnykova VY, Weischenfeldt J, Simon R, Aguiar JA, Alkallas R, Heisler LE, Zhang J, Watson JD, Chua MLK, Fraser M, Favero F, Lawerenz C, Plass C, Sauter G, McPherson JD, van der Kwast T, Korbel J, Schlomm T, Bristow RG, Boutros PC. (2017)
Mitochondrial mutations drive prostate cancer aggression.
Nature Communications 8(1):656. PubMed abstract

Kron KJ, Murison A, Zhou S, Huang V, Yamaguchi TN, Shiah YJ, Fraser M, van der Kwast T, Boutros PC, Bristow RG, Lupien M. (2017)
TMPRSS2-ERG fusion co-opts master transcription factors and activates NOTCH signaling in primary prostate cancer.
Nature Genetics 49(9):1336-1345. PubMed abstract

Chua MLK, Lo W, Pintilie M, Murgic J, Lalonde E, Bhandari V, Mahamud O, Gopalan A, Kweldam CF, van Leenders GJLH, Verhoef EI, Hoogland AM, Livingstone J, Berlin A, Dal Pra A, Meng A, Zhang J, Orain M, Picard V, Hovington H, Bergeron A, Lacombe L, Fradet Y, Têtu B, Reuter VE, Fleshner N, Fraser M, Boutros PC, van der Kwast TH, Bristow RG. (2017)
A Prostate Cancer "Nimbosus": Genomic instability and SChLAP1 dysregulation underpin aggression of intraductal and cribriform subpathologies.
European Urology 72(5):665-674. PubMed abstract

Chua MLK, van der Kwast TH, Bristow RG. (2017)
Intraductal carcinoma of the prostate: anonymous to ominous.
European Urology 72(4):496-498. PubMed abstract

Murphy DG, Risbridger GP, Bristow RG, Sandhu S. (2017)
The evolving narrative of DNA repair gene defects: distinguishing indolent from lethal prostate cancer.
European Urology 71(5):748-749. PubMed abstract

Fraser M, Sabelnykova VY, Yamaguchi TN, Heisler LE, Livingstone J, Huang V, Shiah YJ, Yousif F, Lin X, Masella AP, Fox NS, Xie M, Prokopec SD, Berlin A, Lalonde E, Ahmed M, Trudel D, Luo X, Beck TA, Meng A, Zhang J, D'Costa A, Denroche RE, Kong H, Espiritu SM, Chua ML, Wong A, Chong T, Sam M, Johns J, Timms L, Buchner NB, Orain M, Picard V, Hovington H, Murison A, Kron K, Harding NJ, P'ng C, Houlahan KE, Chu KC, Lo B, Nguyen F, Li CH, Sun RX, de Borja R, Cooper CI, Hopkins JF, Govind SK, Fung C, Waggott D, Green J, Haider S, Chan-Seng-Yue MA, Jung E, Wang Z, Bergeron A, Dal Pra A, Lacombe L, Collins CC, Sahinalp C, Lupien M, Fleshner NE, He HH, Fradet Y, Tetu B, van der Kwast T, McPherson JD, Bristow RG, Boutros PC. (2017)
Genomic hallmarks of localized, non-indolent prostate cancer.
Nature 541(7637):359-364. PubMed abstract

Taylor RA, Fraser M, Livingstone J, Espiritu SM, Thorne H, Huang V, Lo W, Shiah YJ, Yamaguchi TN, Sliwinski A, Horsburgh S, Meng A, Heisler LE, Yu N, Yousif F, Papargiris M, Lawrence MG, Timms L, Murphy DG, Frydenberg M, Hopkins JF, Bolton D, Clouston D, McPherson JD, van der Kwast T, Boutros PC, Risbridger GP, Bristow RG. (2017)
Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories.
Nature Communications 8:13671. PubMed abstract

Chua ML, Bristow RG. (2016)
Testosterone in androgen receptor signaling and DNA repair: enemy or frenemy?
Clinical Cancer Research 22(13):3124-6. PubMed abstract

Gani C, Coackley C, Kumareswaran R, Schütze C, Krause M, Zafarana G, Bristow RG. (2015)
In vivo studies of the PARP inhibitor, AZD-2281, in combination with fractionated radiotherapy: An exploration of the therapeutic ratio.
Radiotherapy and Oncology 116(3):486-94. PubMed abstract

Boutros PC, Fraser M, Harding NJ, de Borja R, Trudel D, Lalonde E, Meng A, Hennings-Yeomans PH, McPherson A, Sabelnykova VY, Zia A, Fox NS, Livingstone J, Shiah YJ, Wang J, Beck TA, Have CL, Chong T, Sam M, Johns J, Timms L, Buchner N, Wong A, Watson JD, Simmons TT, P'ng C, Zafarana G, Nguyen F, Luo X, Chu KC, Prokopec SD, Sykes J, Dal Pra A, Berlin A, Brown A, Chan-Seng-Yue MA, Yousif F, Denroche RE, Chong LC, Chen GM, Jung E, Fung C, Starmans MH, Chen H, Govind SK, Hawley J, D'Costa A, Pintilie M, Waggott D, Hach F, Lambin P, Muthuswamy LB, Cooper C, Eeles R, Neal D, Tetu B, Sahinalp C, Stein LD, Fleshner N, Shah SP, Collins CC, Hudson TJ, McPherson JD, van der Kwast T, Bristow RG. (2015)
Spatial genomic heterogeneity within localized, multifocal prostate cancer.
Nature Genetics 47(7):736-45. PubMed abstract

Lalonde E, Ishkanian AS, Sykes J, Fraser M, Ross-Adams H, Erho N, Dunning MJ, Halim S, Lamb AD, Moon NC, Zafarana G, Warren AY, Meng X, Thoms J, Grzadkowski MR, Berlin A, Have CL, Ramnarine VR, Yao CQ, Malloff CA, Lam LL, Xie H, Harding NJ, Mak DY, Chu KC, Chong LC, Sendorek DH, P'ng C, Collins CC, Squire JA, Jurisica I, Cooper C, Eeles R, Pintilie M, Dal Pra A, Davicioni E, Lam WL, Milosevic M, Neal DE, van der Kwast T, Boutros PC, Bristow RG. (2014)
Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study.
The Lancet Oncology 15(13):1521-32. PubMed abstract

Team

Scientific Officer
Steve Lyons

Postdoctoral Fellow
Richard Rebello

Graduate Student
Ronnie Rodrigues Pereira