Research Summary

For more info, please visit rohitlab.org

Our group's research falls into three overlapping themes:
A. Hypermutation in Cancer
B. Sensitization to Cancer Treatment
C. Oncogene Networks

A. Hypermutation in Cancer
We study hypermutated subtypes of cancer via organoids, cell lines and murine systems. This enables us to investigate diverse aspects of cancer biology including: 1) our ability to model such patients' disease in vitro, ex vivo and in vivo, 2) to understand how oncogenic events functionally combine and cooperate to drive cancer formation and treatment resistance and 3) to experimentally define the determinants within the immune and tumor microenvironments that affect hypermutated tumor growth and response to therapy.

B. Sensitization to Cancer Treatment
Most pooled gene-knockout screens are powered to identify mediators of drug resistance. We are developing modified approaches that are powered instead to identify mediators and mechanisms of increased sensitivity to modern therapies. We have also completed whole-genome screens that suggest differing combinatorial treatment strategies depending on the tumor profile. One such set of results is leading us to investigate how epigenetic modifiers can be targeted in combination with standard-of-care therapies for a subset of prostate cancer patients.

C. Oncogene Networks
There are many protein families for which several members can individually give rise to cancer when dysregulated; for example, the ERG, ETV1 and ETV4 prostate oncogenes and the ERF prostate tumor suppressor (Bose et al, Nature, 2017), are some of the 30 members of the ETS transcription factor family. However, the frequency and mechanism of each alteration has a particular distribution for a given cancer, despite several family members being simultaneously expressed, with overlapping chromatin binding sites etc. Rather than studying individual mechanisms of gene, transcript and protein regulation, we are particularly interested in understanding how such families of cancer drivers compete, cooperate, become redundant and/or get bypassed, as well as determining whether processes occur within clones, or between clones. We also study related networks within normal cells, to understand how their dysregulation gives rise to tumor initiation.

Research Funding

  • September 15, 2018 - August 31, 2023 - Investigating How a Balance of Negative and Positive ETS Factors Controls Prostate Oncogenesis, Principal Investigator. Sponsor: NIH, Sponsor Award ID: K08CA226348
  • September 15, 2018 - August 31, 2023 - Investigating How a Balance of Negative and Positive ETS Factors Controls Prostate Oncogenesis, Principal Investigator. Sponsor: NIH, Sponsor Award ID: K08CA226348
  • September 15, 2018 - August 31, 2023 - Investigating How a Balance of Negative and Positive ETS Factors Controls Prostate Oncogenesis, Principal Investigator. Sponsor: NIH, Sponsor Award ID: K08CA226348
  • September 15, 2018 - August 31, 2023 - Investigating How a Balance of Negative and Positive ETS Factors Controls Prostate Oncogenesis, Principal Investigator. Sponsor: NIH, Sponsor Award ID: K08CA226348

Education

University of Saskatchewan, BSc Dble Honors, 04/1999, Biochemistry, Microbiology & Immunology
University of Toronto, MD, 06/2008, Medicine
University of Toronto, PhD, 11/2008, Molecular Genetics, Jeff Wrana’s Lab
Weill Cornell Medicine, Resident, 06/2010, Internal Medicine, Medical Research Track
Memorial Sloan Kettering, Clinical Fellow, 06/2016, Medical Oncology, Medical Research Track
Memorial Sloan Kettering, Postdoctoral Fellow, 05/2018, Human Oncology, Charles Sawyers’ Lab

Honors & Awards

  • 1999
    Earl of Bessborough Prize for Most Distinguished Graduate Receiving a B.Sc., U of Sask
  • 1999
    Haslam Medal for Most Distinguished Graduate of College of Arts and Sciences, U of Sask
  • 1999
    JF Morgan Memorial Award for Highest Academic Achievement, Microbiology B.Sc., U of Sask
  • 1999
    Merit in Biochemistry Award, Society of Chemical Industry
  • 2004
    Young Investigator Award for Distinguished Project, Canadian Society for Clinical InvestigationScholarship for Cancer Research Conference, ISREC
  • 2005
    George Brown Medical Student Research Day Award, University of Toronto
  • 2006
    Robert and Francine Ruggles Family Graduate Fellowship, University of Toronto
  • 2007
    Dr. Ruth Kurdyak Memorial Medical Alumni Student Award, University of Toronto
  • 2007
    Ruffo Graduate Fellowship for Outstanding Achievement during MD/PhD, University of Toronto
  • 2008
    Lois & K.J.R. Wightman Award for Interest in Internal Medicine, University of Toronto
  • 2011
    John Mendelsohn Housestaff Teaching Award, Memorial Sloan Kettering Cancer Center
  • 2011-2013
    Dana Fellow in Biomedical Research, Clinical Scholars Training Program
  • 2013-2015
    Postdoctoral Research Training Award, US Dept of Defense, Prostate Cancer Program
  • 2013
    Young Investigator Award, Conquer Cancer Foundation of ASCO
  • 2015 - 2019
    Physician Research Training Award, US Dept of Defense, Prostate Cancer Program
  • 2016
    Merit Award in Genitourinary Cancer, Conquer Cancer Foundation of ASCO
  • 2016 – 2019
    Young Investigator Award, Prostate Cancer Foundation

Selected Publications

  1. Adams EJ, Karthaus WR, Hoover E, Liu D, Gruet A, Zhang Z, Cho H, DiLoreto R, Chhangawala S, Liu Y, Watson PA, Davicioni E, Sboner A, Barbieri CE, Bose R, Leslie CS, Sawyers CL. Author Correction: FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes. Nature. 2020 Sep; 585(7826):E20.  View on PubMed
  2. Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjöström M, Aggarwal R, Playdle D, Liao A, Alumkal JJ, Das R, Chou J, Hua JT, Barnard TJ, Bailey AM, Chow ED, Perry MD, Dang HX, Yang R, Moussavi-Baygi R, Zhang L, Alshalalfa M, Laura Chang S, Houlahan KE, Shiah YJ, Beer TM, Thomas G, Chi KN, Gleave M, Zoubeidi A, Reiter RE, Rettig MB, Witte O, Yvonne Kim M, Fong L, Spratt DE, Morgan TM, Bose R, Huang FW, Li H, Chesner L, Shenoy T, Goodarzi H, Asangani IA, Sandhu S, Lang JM, Mahajan NP, Lara PN, Evans CP, Febbo P, Batzoglou S, Knudsen KE, He HH, Huang J, Zwart W, Costello JF, Luo J, Tomlins SA, Wyatt AW, Dehm SM, Ashworth A, Gilbert LA, Boutros PC, Farh K, Chinnaiyan AM, Maher CA, Small EJ, Quigley DA, Feng FY. The DNA methylation landscape of advanced prostate cancer. Nat Genet. 2020 08; 52(8):778-789.  View on PubMed
  3. Ryan MJ, Bose R. Genomic Alteration Burden in Advanced Prostate Cancer and Therapeutic Implications. Front Oncol. 2019; 9:1287.  View on PubMed
  4. Adams EJ, Karthaus WR, Hoover E, Liu D, Gruet A, Zhang Z, Cho H, DiLoreto R, Chhangawala S, Liu Y, Watson PA, Davicioni E, Sboner A, Barbieri CE, Bose R, Leslie CS, Sawyers CL. FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes. Nature. 2019 07; 571(7765):408-412.  View on PubMed
  5. Kelly W, Godwin J, Hoffman-Censits J, Knudsen K, De Leeuw R, Leiby B, Southwell T, Hubert C, Smith D, Chatta G, Agahalar J, Scher H, Bose R, Autio K, Abida W, Slovin S, The Prostate Cancer Clinical Trials Consortium. Journal of Clinical Oncology. c15-153: Randomized phase IB/II study of enzalutamide with and without ribociclib in patients with metastatic castrate resistant, chemotherapy naïve prostate cancer that retains RB expression. 2018.  View on PubMed
  6. Bose R, Karthaus WR, Armenia J, Abida W, Iaquinta PJ, Zhang Z, Wongvipat J, Wasmuth EV, Shah N, Sullivan PS, Doran MG, Wang P, Patruno A, Zhao Y, International SU2C/PCF Prostate Cancer Dream Team , Zheng D, Schultz N, Sawyers CL. ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis. Nature. 2017 06 29; 546(7660):671-675.  View on PubMed
  7. Viloria-Petit AM, David L, Jia JY, Erdemir T, Bane AL, Pinnaduwage D, Roncari L, Narimatsu M, Bose R, Moffat J, Wong JW, Kerbel RS, O'Malley FP, Andrulis IL, Wrana JL. A role for the TGFbeta-Par6 polarity pathway in breast cancer progression. Proc Natl Acad Sci U S A. 2009 Aug 18; 106(33):14028-33.  View on PubMed
  8. Narimatsu M, Bose R, Pye M, Zhang L, Miller B, Ching P, Sakuma R, Luga V, Roncari L, Attisano L, Wrana JL. Regulation of planar cell polarity by Smurf ubiquitin ligases. Cell. 2009 Apr 17; 137(2):295-307.  View on PubMed
  9. Bose R, Wrana JL. Regulation of Par6 by extracellular signals. Curr Opin Cell Biol. 2006 Apr; 18(2):206-12.  View on PubMed
  10. Wang HR, Ogunjimi AA, Zhang Y, Ozdamar B, Bose R, Wrana JL. Degradation of RhoA by Smurf1 ubiquitin ligase. Methods Enzymol. 2006; 406:437-47.  View on PubMed
  11. Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL. High-throughput mapping of a dynamic signaling network in mammalian cells. Science. 2005 Mar 11; 307(5715):1621-5.  View on PubMed
  12. Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL. Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science. 2005 Mar 11; 307(5715):1603-9.  View on PubMed
  13. Bose R, Hwang SW. Income and spending patterns among panhandlers. CMAJ. 2002 Sep 03; 167(5):477-9.  View on PubMed
  14. Bose R, Ahmad A, Dicks A, Novak M, Kayser K, McClelland R. Spectroscopic characterization by laser flash photolysis of electrophilic intermediates derived from 4-aminostilbenes. Stilbene "nitrenium" ions and quinone methide imines. Journal of the Chemical Society, Perkin Transactions 2. 1999; (8):1591 - 1600.  View on PubMed

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