Joshi Alumkal

Joshi Alumkal, M.D.

Professor of Internal Medicine

Biography

Dr. Alumkal spent most of his childhood and early adulthood in Texas. He graduated summa cum laude from the University of Texas with a B.A. in Biology. Then, he received his medical degree from Baylor College of Medicine. He completed an internship, residency, and chief residency at UT Southwestern Medical Center. After completing a clinical fellowship in Medical Oncology at Johns Hopkins University, Dr. Alumkal completed a post-doctoral fellowship focused on cancer epigenetics in the Jim Herman Laboratory at Johns Hopkins. Dr. Alumkal joined the Knight Cancer Institute Prostate Cancer Research Program at Oregon Health & Science University (OHSU) in 2007 and became the co-Leader of the Program in 2013. In 2014, Dr. Alumkal was honored with the Richard T. Jones New Investigator Award for exceptional promise early in a career in biomedical research in Oregon. He was also named the inaugural holder of the Wayne D. Kuni and Joan E. Kuni Endowed Chair for Prostate Cancer Research at OHSU in 2017.

In 2019, Dr. Alumkal re-located to the University of Michigan to lead the Prostate/Genitourinary Medical Oncology Section in the Division of Hematology-Oncology and the Rogel Cancer Center, where he is a Professor of Internal Medicine. He was named a Rogel Cancer Center Rogel Scholar in 2019.

Research Interests

Elucidating the role of the histone demethylase protein lysine specific demethylase 1 (LSD1) in the evolution of lethal castration-resistant prostate cancer (CRPC) is one focus of our lab's research. Our work demonstrates that the LSD1 protein promotes progression of CRPC. Furthermore, we have determined that LSD1 is particularly important in a virulent CRPC subset called neuroendocrine prostate cancer (NEPC). Currently, we are focused on three major areas: a) clarifying mechanisms by which LSD1 regulates transcription in NEPC cells, b) identifying key LSD1 cofactors in NEPC that potentiate LSD1’s function, 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 of LSD1 inhibition alone or in combination with rational strategies in the near-term.

Identifying mechanisms of resistance to the novel androgen receptor (AR) antagonist enzalutamide is another key project in our lab. We were among the first to test the AR antagonist enzalutamide clinically. This drug is now approved for patients with CRPC. However, one-third of patients never respond, and progression is universal. Using a prospective, investigator-initiated clinical trial that we led, we determined that de novo resistant tumors harbor an AR activity-low, stemness program. Currently, we are focused on using representative cell lines and mouse models to clarify critical factors that promote this program and that confer enzalutamide resistance (using both pharmacologic and genetic approaches). Our goals are to: a) develop rational combinations of drugs to block this stemness program and re-sensitize cells to enzalutamide , b) develop non-invasive biomarkers that will help identify patients least likely to respond to enzalutamide treatment, c) develop clinical trials of rational combinations in patients who are ideally-suited for these combinations.

Another potential therapeutic strategy in CRPC is BET bromodomain inhibition. We were the first to demonstrate the efficacy of inhibiting the BET bromodomain chromatin reader proteins in prostate cancer. Our more recent work using pre-clinical models and a phase I clinical trial we led demonstrates that BET bromodomain inhibitors are a promising class of drugs to block AR-independent prostate cancer cell survival. Currently, we are focused on: a) understanding the critical cofactors that cooperate with BET bromodomain proteins, b) developing rational drug combinations to augment the anti-tumor activity of BET bromodomain inhibition, and c) developing phase I clinical trials of these novel combinations.

Research Opportunities for Rotating Students

Our lab is is currently recruiting rotating PIBS students for the following projects: 1) Developing bromodomain inhibitor combination therapies, and 2) Identifying targetable factors that mediate enzalutamide resistance.