Research Profile: Joshua Russo, MD, PhD

About Joshua Russo, MD, PhD

Dr. Joshua RussoDr. Josh Russo joined the Balk laboratory in 2015. His broad interest is in studying prostate cancer development and progression using model systems with validation through pathological and molecular analysis of clinical materials. The goal of his current research is to identify novel mechanisms of resistance to androgen deprivation therapy (ADT) in metastatic castration-resistant prostate cancer (mCRPC), with an emphasis on the post-abiraterone/enzalutamide setting. Using castration-resistant xenograft and cell line models he discovered a possible role for the downregulation of the dipeptidase DPP4 and upregulation of HER2 receptor tyrosine kinase signaling in mediating castration-resistance and prostate cancer progression.  His continuing studies will attempt to interrogate DPP4 and HER2 as targets for treatment in men with mCRPC.

In addition to these studies, Dr. Russo also plans to expand his research into two new areas. The first area will focus on the role of androgen receptor (AR) splice variants as drivers of prostate cancer disease progression. As part of the work to identify the pro-survival pathways driven by AR splice variants, he is interrogating several models of prostate cancer progression developed in the lab including the enzalutamide-resistant human prostate cancer cell line, VCaP-16 and the AER VCaP xenograft model resistant to duel treatment with abiraterone and enzalutamide. He hopes to identify AR-variant specific transcriptional regulators, epigenetic modifiers, and alternative growth factor signaling pathways that are upregulated in the castration-resistant setting and can be targeted with available therapies. The second area will focus on defining the clonal heterogeneity of different metastatic sites within individual prostate cancer patients. This project will take advantage of the Rapid Autopsy Program for Genitourinary Malignancies at Beth Israel Deaconess Medical Center (DFCI Protocol # 15-441), on which Dr. Russo is a co-investigator. The goal of this study is to collect specimens of heavily-treated, castration-resistant metastatic prostate cancer from multiple sites within an individual patient and use a combination of immunohistochemistry, RNA sequencing, and whole exome sequencing to determine the clonal relationships between different metastatic sites and identify novel disease-driving mutations and signaling pathways.