Rohit Bose, MD, PhD

Assistant Professor
Anatomy

Please visit Rohit Bose's UCSF lab website at rohitlab.org for more information.

My lab'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, rather than studying them individually. This era of tumor profiling, in which each biopsy leads to a list of potential oncogenic alterations, requires such a contextual map, 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.

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

Websites

Publications: 

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

Oncogenic mutations alter the chromatin landscape, perturb luminal differentiation programs, and confer distinct prostate cancer phenotypes

In revision

Adams E, Karthaus W, Hoover E, DiLoreto R, Liu D, Liu Y, Watson P, Davicioni E, Sboner A, Barberi C, Bose R, Leslie C, Sawyers C

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

A role for the TGFbeta-Par6 polarity pathway in breast cancer progression.

Proceedings of the National Academy of Sciences of the United States of America

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

Regulation of planar cell polarity by Smurf ubiquitin ligases.

Cell

Narimatsu M, Bose R, Pye M, Zhang L, Miller B, Ching P, Sakuma R, Luga V, Roncari L, Attisano L, Wrana JL