Rohit Bose, MD, PhD

Assistant Professor
Anatomy
Research Overview: 

I’m a practicing medical oncologist with one half-day clinic seeing patients with advanced and metastatic prostate cancer.  Correspondingly, our group's bench research falls into three overlapping themes:

A. Tumor Evolution
B. Sensitization to Cancer Treatment
C. Oncogene Networks

A. Tumor Evolution
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, 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.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Human Genetics
Research Summary: 
We study tumor evolution, drug sensitization and oncogene network alterations in patients in order to improve precision medicine therapies for hormone-related and genitourinary cancers.

Websites

Publications: 

The DNA methylation landscape of advanced prostate cancer.

Nature genetics

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

FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

Nature

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

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

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

ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis.

Nature

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, Zheng D, Schultz N, Sawyers CL