Srinivas Viswanathan
We study the pathways that drive cancer initiation, progression, and drug resistance. We employ both genomic and functional genetic technologies to identify dysregulated pathways in cancer and explore how these can be targeted for therapeutic benefit. Our work combines genomic profiling of primary tissue specimens with functional approaches in both in vitro and in vivo systems to uncover new cancer drivers and their associated therapeutic vulnerabilities.
Cancer genomics and epigenomics: We use various next-generation bulk and single-cell sequencing platforms to define the genomic and epigenomic landscape of prostate and kidney cancers. In prostate cancer, we focus on molecular alterations that drive castration-resistant prostate cancer, the lethal and hormone-resistant stage of the disease. Amongst kidney cancers, we have a special interest in rarer molecular subtypes, including the genetics and biology of translocation renal cell carcinoma (tRCC), an aggressive cancer driven by oncogenic gene fusions of an MiT/TFE family transcription factor. Our aim is to understand how these fusions work in order to find ways to target this cancer more effectively.
Functional genetic screens to uncover cancer vulnerabilities: We employ a range of genetic techniques to systematically identify cancer vulnerabilities and to mechanistically study cancer driver genes, with a focus on prostate and kidney cancers. Current efforts include identifying synthetic lethal therapeutic targets, finding vulnerabilities associated with therapy-resistance, discovering subtype-specific dependencies, and mapping the functions of key driver genes in these cancers.
Sex differences in cancer: Many cancers show differences in incidence or outcomes between males and females. We use prostate cancer (male-exclusive) and tRCC (female-predominant) as models to explore how genetic alterations, particularly of the sex chromosomes, may underlie these differences.
Our overarching goal is to address fundamental questions in cancer biology that can inspire the development of new, rational cancer therapies that improve patient outcomes.