OHSU

Research Interests

  • Prostate cancer
  • Epigenetics
  • Treatment Resistance

Our laboratory focuses on identifying mechanisms by which prostate cancer progresses to the lethal form of the disease that is resistant to male hormone- lowering therapies. We believe molecular methods can be used to understand this process. Our goal is to apply insights from the lab to clinical trials for patients.

  1. The role of the histone demethylase protein lysine specific demethylase 1 (LSD1) in the evolution of castration-resistant prostate cancer (CRPC). Our work demonstrates that the LSD1 protein promotes progression of CRPC. Currently, we are focused on three major areas: a) identifying the critical LSD1 transcriptional network in CRPC cells, b) identifying non-histone substrates demethylated by LSD1 that contribute to CRPC progression, c) and testing novel, specific LSD1 inhibitors in vitro and in vivo. Our goal is to translate these findings to a phase I clinical trial with these LSD1 inhibitors in the near-term.
  2. Identifying mechanisms of resistance to the novel androgen receptor (AR) antagonist enzalutamide. We were among the first to test the AR antagonist enzalutamide clinically. This drug is now approved for patients with CRPC. However, 50% of patients never respond and progression is universal. We are focused on using both cell line model systems and a prospective clinical trial with metastatic tissue collection to clarify molecular mechanisms of de novo and acquired enzalutamide resistance. Our goals are to: a) develop biomarkers that will help identify patients most likely to respond to enzalutamide treatment and b) to develop rational combinations of drugs to overcome specific enzalutamide resistance mechanisms.
  3. BET bromodomain inhibition as a therapeutic strategy in CRPC. We were the first to demonstrate the efficacy of BET bromodomain inhibition in prostate cancer. Currently, we are focused on: a) understanding the critical bromodomain responsive pathways whose modulation accounts for the anti-tumor efficacy of BET bromodomain inhibition, b) clarifying the emergent cellular properties affected by BET bromodomain inhibition, and c) testing BET bromodomain inhibitors in vivo.