Dr. 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.
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Postdoctoral Research Fellowship: Beth Israel Deaconess Medical Center/Harvard Medical School: 2015-2018
Anatomical Pathology Residency: Anatomical and Clinical Pathology Residency Program, Beth Israel Deaconess Medical Center: 2014-2015
MD/PhD: Tufts University School of Medicine (MD)/ Tufts Sackler School of Biomedical Sciences (PhD, Cell and Developmental Biology): 2001-2011
B.S.: Biochemistry, Bucknell University: 1997-2001
David Mazzone Research Awards Program Career Enhancement Award, “DPP4-Mediated Mechanisms of Resistance in Castration-Resistant Prostate Cancer”: 2018-2019
Department of Defense, Congressionally Directed Medical Research Program, Prostate Cancer Research Program, Early Investigator Award (W81XWH-17-PCRP-EIRA), “Mechanisms of Resistance to Androgen Deprivation Therapy in Advanced Castration-Resistant Prostate Cancer (CRPC)”: 2018-2020
Prostate Cancer Foundation, Young Investigator Award, “HER-2-mediated Mechanisms of Abiraterone and Enzalutamide Resistance in Advanced Metastatic Prostate Cancer”: 2018-2021
- Sharp A, Coleman I, Yuan W, Sprenger C, Dolling D, Nava Rodrigues D, Russo JW, Figueiredo I, Bertan C, Seed G, Riisnaes R, Uo T, Neeb A, Welti J, Morrissey C, Carreira S, Luo J, Nelson PS, Balk, SP, True LD, DeBono J, and Plymate SR. Androgen receptor splice variant-7 expression emerges with castration resistance in prostate cancer. (2018) J Clin Invest. Epub ahead of print. PMID: 30334814.
- Russo JW, Gao C, Bhasin SS, Voznesensky OS, Calagua C, Arai S, Nelson PS, Montgomery B, Mostaghel EA, Corey E, Taplin ME, Ye H, Bhasin M, and Balk SP. Downregulation of Dipeptidyl Peptidase 4 accelerates progression of castration-resistant prostate cancer. (2018) Cancer Research. 78(22):6354-6362. PMID: 30242112.
- Russo JW, Liu X, Ye H, Calagua C, Chen S, Voznesensky O, Condulis J, Ma F, Taplin ME, Einstein DJ, Balk SP, and Chen S. Phosphorylation of androgen receptor 81 is associated with its reactivation in castration-resistant prostate cancer. (2018) Cancer Lett. 438:97-104. PMID: 30217568.
- Sowalsky AG, Ye H, Bhasin M, Van Allen EM, Loda M, Lis RT, Montaser-Kouhsari L, Calagua C, MA F, Russo JW, Schaefer RJ, Voznesensky OS, Zhang Z, Bubley GJ, Montogomery B, Mostaghel EA, Nelson PS, Taplin ME, and Balk SP. Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations. (2018) Cancer Research. 78(16):4716-4730. PMID: 29921690.
- Fiaturi N, Russo JW, Nielsen HC, and Castellot JJ. CCN5 in alveolar epithelial proliferation and differentiation during neonatal lung oxygen injury. (2018) J Cell Commun Signal. 12(1):217-229. PMID: 29349730.
- *Calagua C, *Russo J, Yue S, Schaefer R, Lis R, Zhenwei Z, Mahoney K, Bubley G, Loda M, Taplin ME, Balk S, and Ye H. Expression of PD-L1 in Hormone-naïve and Treated PCa Patients Receiving Neoadjuvant Abiraterone Acetate plus Prednisone and Leuprolide. (2017) Clin Cancer Res. 23(22):6812-6822. PMID: 28893901.
*First authors contributed equally to this work.
- Sowalsky AG, Kissick HT, Gerrin S, Schaefer R, Xia Z, Russo JW, Arredouani MS, Bubley, GJ, Sanda MG, Li W, Ye H, and Balk SP. Gleason Score 7 Prostate Cancers Emerge Through Branched Evolution of Clonal Gleason Pattern 3 and 4. (2017) Clin Cancer Res. 23(14):3823-3822 PMID: 28119368.
- Liu X, Gao Y, Ye H, Gerrin S, Ma F, Wu Y, Zhang T, Russo J, Cai C, Yuan X, Liu J, Chen S, and Balk SP. Positive feedback loop mediated by protein phosphatase 1α mobilization of P-TEFb and basal CDK1 drives androgen receptor in prostate cancer. (2017) Nucleic Acids Res. 45(7):3738-3751. PMID: 28062857
- Wiesman KC, Wei L, Baughman C, Russo J, Gray MR, and Castellot JJ. CCN5, a secreted protein, localizes to the nucleus. (2010) J Cell Commun Signal. 4(2):91-8. PMID: 20531984.
- Wei L, McKeon F, Russo JW, Lemire J, and Castellot J. Domain-and species-specific monoclonal antibodies recognize the Von Willebrand Factor-C domain of CCN5. (2009) J Cell Commun Signal. 3(1):65-77. PMID: 19401828.
- Salem RO, Refaai MA, Cluette-Brown JE, Russo JW, and Laposata M. Fatty acid ethyl esters in liver and adipose tissues as postmortem markers of ethanol intake. (2001) Clin Chem. 47(4):722-5. PMID:11274023.