Scott's research has focused on using high-throughput techniques to characterize the cancer genome and transcriptome to identify cancer-specific aberrations to better understand cancer biology and identify clinically relevant biomarkers and therapeutic targets. His most important contribution has been discovering TMPRSS2:ETS gene fusions in prostate cancer, which play a fundamental role in prostate cancer development and have potential as biomarkers for early detection, risk stratification and therapeutic targeting. He has led studies characterizing the diversity of gene fusions, their in vitro function, and generation and characterization of transgenic mouse models. He is interested in translating research discoveries and has led the clinical validation and implementation of TMPRSS2:ERG fusions as diagnostic and early detection biomarkers.

His ongoing research interests include the comprehensive molecular subtyping of prostate cancer, and he has led the first exome based sequencing study of lethal, castration resistant prostate cancer. Research in our laboratory utilizes integrative high-throughput approaches including next generation sequencing using Ion Torrent sequencers to molecularly profile genitourinary malignancies, including bladder, penile and adrenocortical carcinoma, as well as other cancer types. We have led the development and validation of several DNA and RNA based panels that can be used to implement precision medicine for patients with cancer at scale.

Lastly, projects to functionally validate intriguing candidates from our studies and other large scale cancer sequencing projects are ongoing. We are particularly interested in understanding the molecular mediators of the transition between androgen receptor dependent prostate cancer and the more aggressive androgen receptor independent prostate cancer.