Our laboratory at the Dana-Farber Cancer Institute is focused on mechanistic study of the pathways that underlie cancer initiation, progression, and drug resistance with a focus on genitourinary cancers, particularly cancers of the prostate and kidney. We apply both genomic and functional genetic technologies to discover dysregulated pathways in cancer and seek to delineate how these pathways can be modulated for therapeutic benefit.  Work in the laboratory integrates genomic profiling of primary tissue specimens with functional approaches in in vitro and in vivo systems in order to discover new drivers and therapeutic vulnerabilities of genitourinary cancers. Currently, we have three main areas of cancer focus:

Prostate Cancer: Signaling via the androgen receptor (AR) is the chief driver of prostate cancer across disease states. Through the genomic profiling of patient specimens, we are dissecting genetic and epigenetic alterations that sustain AR signaling in advanced prostate cancer. In concert, we apply genome-scale functional genetic screening to discover new modes by which this pathway can be therapeutically targeted. 

MiT/TFE Translocation Renal Cell Carcinoma (tRCC): Our laboratory has a special interest in the genetics and biology of tRCC, a rare but highly aggressive subtype of kidney cancer without effective therapies. This cancer is driven by oncogenic gene fusions involving a transcription factor in the MiT/TFE family, usually TFE3 located on chromosome Xp11.2. We use a combination of genomic, functional genetic, and biochemical approaches to understand how MiT/TFE fusions exert their oncogenic effects and seek to discover ways in which this cancer can be rationally targeted. 

Sex bias in cancer: Both prostate cancer and tRCC share the feature of having a strong driver oncogene on chromosome X. An emerging interest in the laboratory is in using both of these diseases to more broadly understand how genetic alterations – specifically on the sex chromosomes – may underlie sex differences in cancer incidence or pathogenesis.

The overarching goal of these and other projects in the lab is to explore fundamental questions in cancer biology that can inspire the development of rational cancer therapeutic strategies with the potential to impact clinical outcomes for patients.