Education

Recognition

Research Interests

Mechanisms of castration-resistant prostate cancer development; Resistance to nuclear hormone receptor-targeted therapy in prostate cancer; dysregulated transcription factor biology in prostate cancer; biology of prostate cancer health disparities in African-American men.

The development of androgen receptor (AR)-targeted drug resistance in prostate cancer (PC) remains therapeutically challenging, and mechanisms of resistance owing to this challenge are likely to involve both AR-dependent and -independent signaling nodes. Genomic analyses performed by our group in ARSI-resistant PC cells reveals FOXP1, a transcription factor and tumor suppressor that negatively regulates AR signaling, as a dysregulated gene in this context. Loss of FOXP1 expression has been associated with poor survival in PC, and interestingly, an increased risk of aggressive PC disease particularly for African-American men. Through a comprehensive investigation of FOXP1-mediated biology in PC, the overarching objectives of our studies are to: 1) delineate the basis of irregular FOXP1 biology for AR-dependent and -independent transcriptional programming, 2) discover new drug targets that mitigate FOXP1 loss-mediated behavior, and 3) determine the extent to which FOXP1 loss drives ethnicity-dependent, aggressive PC. The work being conducted towards our objective employs a host of high-throughput, cutting-edge technologies such as ATAC-Seq, ChIP-Seq, ChIP-RIME, RNA-Seq, spatial transcriptomic profiling, genome-wide CRISPR screens and diverse drug compound screens to translate basic findings regarding FOXP1-mediated PC biology into actionable intelligence to maximize positive clinical outcomes. Through this work, we ultimately seek to develop FOXP1 loss as a bona fide driver and biomarker of aggressive PC, where we hope to demonstrate the efficacy of FOXP1 loss to serve as a predictor for sensitivity to novel therapies, particularly in AA men. Importantly, data resulting from our work will become a key resource upon which near-term clinical trials for improved PC patient management can be established, and future hypotheses that seek to study disparate PC biology among African-American men can be tested.

Assistant