Research Abstract

Dr. Russo's current scientific work focuses on elucidating mechanisms of resistance to second-line androgen deprivation therapy (ADT) agents abiraterone (Abi) and enzalutamide (Enza) in advanced castration-resistant prostate cancer (CRPC). Dr. Russo has several ongoing projects including work to establish a role for downregulation of the cell-surface dipeptidase, DPP4, as a driver of ADT resistance in advanced CRPC. DPP4’s dipeptidase activity is known to target many cytokines and growth factors for degradation, including ligands for receptor tyrosine kinases (RTK’s). Dr. Russo has published work showing that DPP4 is strikingly downregulated in CRPC and that this downregulation is associated with increases in RTK signaling. Further, inhibiting DPP4’s peptidase activity results in earlier relapse in xenograft and PDX models of CRPC. Another of Dr. Russo's ongoing projects is interrogating ErbB2 signaling in advanced CRPC with a focus on canonical ErbB2/ErbB3 signaling driven by NRG1 ligand as well as signaling through an ErbB2 splice variant d16ERBB2 in xenograft/cell line models. Dr. Russo has also collaborated with other investigators within the DF/HCC and at outside institutions on additional projects including genomic and transcriptomic comparison of Gleason 3 and Gleason 4 primary prostate cancer and neoadjuvant-abiraterone-leuprolide treated samples, interaction of phospho-AR (Ser81) with CDK1 in castration-resistance, defining an association between abiraterone treatment and PD-L1 expression in prostate cancer, correlating expression of an AR variant (AR-V7) with prostate cancer progression, developing and testing CDK9 inhibitors, and demonstrating TGF-beta signaling as a driver of advanced CRPC.