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Joshua Russo, M.D.

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Overview
Dr. Josh Russo's 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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Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Einstein DJ, Arai S, Calagua C, Xie F, Voznesensky O, Capaldo BJ, Luffman C, Hecht JL, Balk SP, Sowalsky AG, Russo JW. Metastatic Castration-Resistant Prostate Cancer Remains Dependent on Oncogenic Drivers Found in Primary Tumors. JCO Precis Oncol. 2021; 5. PMID: 34568716; PMCID: PMC8457789.
    Citations: 3     Fields:    Translation:Humans
  2. Liang J, Wang L, Poluben L, Nouri M, Arai S, Xie L, Voznesensky OS, Cato L, Yuan X, Russo JW, Long HW, Brown M, Chen S, Balk SP. Androgen receptor splice variant 7 functions independently of the full length receptor in prostate cancer cells. Cancer Lett. 2021 10 28; 519:172-184. PMID: 34256096; PMCID: PMC8403646.
    Citations: 2     Fields:    Translation:HumansCells
  3. He MX, Cuoco MS, Crowdis J, Bosma-Moody A, Zhang Z, Bi K, Kanodia A, Su MJ, Ku SY, Garcia MM, Sweet AR, Rodman C, DelloStritto L, Silver R, Steinharter J, Shah P, Izar B, Walk NC, Burke KP, Bakouny Z, Tewari AK, Liu D, Camp SY, Vokes NI, Salari K, Park J, Vigneau S, Fong L, Russo JW, Yuan X, Balk SP, Beltran H, Rozenblatt-Rosen O, Regev A, Rotem A, Taplin ME, Van Allen EM. Transcriptional mediators of treatment resistance in lethal prostate cancer. Nat Med. 2021 03; 27(3):426-433. PMID: 33664492; PMCID: PMC7960507.
    Citations: 23     Fields:    Translation:HumansCells
  4. Richters A, Doyle SK, Freeman DB, Lee C, Leifer BS, Jagannathan S, Kabinger F, Koren JV, Struntz NB, Urgiles J, Stagg RA, Curtin BH, Chatterjee D, Mathea S, Mikochik PJ, Hopkins TD, Gao H, Branch JR, Xin H, Westover L, Bignan GC, Rupnow BA, Karlin KL, Olson CM, Westbrook TF, Vacca J, Wilfong CM, Trotter BW, Saffran DC, Bischofberger N, Knapp S, Russo JW, Hickson I, Bischoff JR, Gottardis MM, Balk SP, Lin CY, Pop MS, Koehler AN. Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors. Cell Chem Biol. 2021 02 18; 28(2):134-147.e14. PMID: 33086052.
    Citations: 14     Fields:    Translation:AnimalsCells
  5. Zhang Z, Karthaus WR, Lee YS, Gao VR, Wu C, Russo JW, Liu M, Mota JM, Abida W, Linton E, Lee E, Barnes SD, Chen HA, Mao N, Wongvipat J, Choi D, Chen X, Zhao H, Manova-Todorova K, de Stanchina E, Taplin ME, Balk SP, Rathkopf DE, Gopalan A, Carver BS, Mu P, Jiang X, Watson PA, Sawyers CL. Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer. Cancer Cell. 2020 08 10; 38(2):279-296.e9. PMID: 32679108; PMCID: PMC7472556.
    Citations: 46     Fields:    Translation:HumansAnimalsCells
  6. Russo JW, Nouri M, Balk SP. Androgen Receptor Interaction with Mediator Complex Is Enhanced in Castration-Resistant Prostate Cancer by CDK7 Phosphorylation of MED1. Cancer Discov. 2019 11; 9(11):1490-1492. PMID: 31676563; PMCID: PMC6830511.
    Citations: 6     Fields:    Translation:HumansCells
  7. Russo JW, Balk SP. Initiation and Evolution of Early Onset Prostate Cancer. Cancer Cell. 2018 12 10; 34(6):874-876. PMID: 30537509.
    Citations: 6     Fields:    Translation:HumansCells
  8. Sharp A, Coleman I, Yuan W, Sprenger C, Dolling D, Rodrigues DN, 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, de Bono JS, Plymate SR. Androgen receptor splice variant-7 expression emerges with castration resistance in prostate cancer. J Clin Invest. 2019 01 02; 129(1):192-208. PMID: 30334814; PMCID: PMC6307949.
    Citations: 113     Fields:    Translation:HumansAnimalsCells
  9. 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, Balk SP. Downregulation of Dipeptidyl Peptidase 4 Accelerates Progression to Castration-Resistant Prostate Cancer. Cancer Res. 2018 11 15; 78(22):6354-6362. PMID: 30242112; PMCID: PMC6239953.
    Citations: 21     Fields:    Translation:HumansAnimalsCells
  10. Russo JW, Liu X, Ye H, Calagua C, Chen S, Voznesensky O, Condulis J, Ma F, Taplin ME, Einstein DJ, Balk SP, Chen S. Phosphorylation of androgen receptor serine 81 is associated with its reactivation in castration-resistant prostate cancer. Cancer Lett. 2018 12 01; 438:97-104. PMID: 30217568; PMCID: PMC6186500.
    Citations: 7     Fields:    Translation:HumansAnimalsCells
  11. 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, Montgomery B, Mostaghel EA, Nelson PS, Taplin ME, Balk SP. Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations. Cancer Res. 2018 08 15; 78(16):4716-4730. PMID: 29921690; PMCID: PMC6095796.
    Citations: 25     Fields:    Translation:Humans
  12. Fiaturi N, Russo JW, Nielsen HC, Castellot JJ. CCN5 in alveolar epithelial proliferation and differentiation during neonatal lung oxygen injury. J Cell Commun Signal. 2018 Mar; 12(1):217-229. PMID: 29349730; PMCID: PMC5842201.
    Citations: 7     
  13. Calagua C, Russo J, Sun Y, Schaefer R, Lis R, Zhang Z, Mahoney K, Bubley GJ, Loda M, Taplin ME, Balk SP, Ye H. Expression of PD-L1 in Hormone-naïve and Treated Prostate Cancer Patients Receiving Neoadjuvant Abiraterone Acetate plus Prednisone and Leuprolide. Clin Cancer Res. 2017 Nov 15; 23(22):6812-6822. PMID: 28893901.
    Citations: 44     Fields:    Translation:HumansCells
  14. Liu X, Gao Y, Ye H, Gerrin S, Ma F, Wu Y, Zhang T, Russo J, Cai C, Yuan X, Liu J, Chen S, Balk SP. Positive feedback loop mediated by protein phosphatase 1a mobilization of P-TEFb and basal CDK1 drives androgen receptor in prostate cancer. Nucleic Acids Res. 2017 04 20; 45(7):3738-3751. PMID: 28062857; PMCID: PMC5397168.
    Citations: 15     Fields:    Translation:HumansCells
  15. Sowalsky AG, Kissick HT, Gerrin SJ, Schaefer RJ, Xia Z, Russo JW, Arredouani MS, Bubley GJ, Sanda MG, Li W, Ye H, Balk SP. Gleason Score 7 Prostate Cancers Emerge through Branched Evolution of Clonal Gleason Pattern 3 and 4. Clin Cancer Res. 2017 Jul 15; 23(14):3823-3833. PMID: 28119368; PMCID: PMC5511561.
    Citations: 21     Fields:    Translation:HumansCells
  16. Russo JW, Castellot JJ. CCN5: biology and pathophysiology. J Cell Commun Signal. 2010 Oct; 4(3):119-30. PMID: 21063502.
    Citations: 29     
  17. Wiesman KC, Wei L, Baughman C, Russo J, Gray MR, Castellot JJ. CCN5, a secreted protein, localizes to the nucleus. J Cell Commun Signal. 2010 Jun; 4(2):91-8. PMID: 20531984.
    Citations: 14     
  18. Wei L, McKeon F, Russo JW, Lemire J, Castellot J. Domain-and species-specific monoclonal antibodies recognize the Von Willebrand Factor-C domain of CCN5. J Cell Commun Signal. 2009 Mar; 3(1):65-77. PMID: 19401828.
    Citations: 4     
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.