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/NCI, 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/NCI, 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/NCI, 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/NCI, 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