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Jingsong Zhang, MD, PhD

Academic Rank: Associate Member

Overview


Discipline

    • Genitourinary Oncology
    • Cancer Physiology
    • Molecular Medicine Program
    • Cancer Chemoprevention Research Interest Group
    • Cancer Imaging and Technology
    • Evolutionary Therapy

Education & Training

Board Certification:

  • Medical Oncology

Fellowship:

  • Peking Union Medical College, MD -
  • University of Southern California, PhD - Pathobiology
  • New York Downtown Hospital, Intern/Resident - Internal Medicine
  • University of Michigan Comprehensive Cancer Center, Fellow - Hematology-Oncology
Research

Dr. Zhang’s research focuses on 1) defining and characterizing deregulated pathways with therapeutic relevance in subsets of human cancers, and 2) developing and implementing biomarker-driven therapeutics into patient-based therapeutic trials.He aims to identify the DNA damage repair pathways that metastatic prostate cancers rely on and then assess the therapeutic potential of targeting these pathways. Preliminary data indicates that blocking key proteins in DDR pathways with PARP inhibitor, DNA-PK inhibitor or BRCA1 shRNA sensitized metastatic prostate cancer cells to DNA damaging chemotherapy drugs. The synergistic combinations are being tested in metastatic prostate cancer mouse models.Secondly, Dr. Zhang is evaluating r-H2AX as a prognostic or predictive marker.Unrepaired DNA single strand breaks will be converted to double strand breaks (DSB) during DNA replication, and r-H2AX is a well-known marker for DNA DSB.  High levels of r-H2AX expression in prostate cancers would correlate with diminished DNA repair pathways and therefore high mutation rates.  Dr. Zhang and colleagues will develop a scoring system for r-H2AX expression by immunohistochemistry and correlate that with patients’ clinical outcomes. Based on initial results, the value of r-H2AX can be further evaluated in larger patient cohorts with multi-variant analysis.  Assays also can be developed to detect r-H2AX in circulating tumor cells.

Publications

  • Li R, Sundi D, Zhang J, Kim Y, Sylvester RJ, Spiess PE, Poch MA, Sexton WJ, Black PC, McKiernan JM, Steinberg GD, Kamat AM, Gilbert SM. Systematic Review of the Therapeutic Efficacy of Bladder-preserving Treatments for Non-muscle-invasive Bladder Cancer Following Intravesical Bacillus Calmette-Guérin. Eur Urol. 2020 Sep.78(3):387-399. Pubmedid: 32143924.
  • Jain RK, Skelton WP, Zhang J. Emerging Treatment Options for the Treatment of Metastatic Urothelial Cancer: Therapeutic Potential of Enfortumab Vedotin. Cancer Manag Res. 2020 Sep.12:8379-8386. Pubmedid: 32982431. Pmcid: PMC7494003.
  • Yuan Z, Fernandez D, Dhillon J, Abraham-Miranda J, Awasthi S, Kim Y, Zhang J, Jain R, Serna A, Pow-Sang JM, Poch M, Li R, Manley B, Fink A, Naghavi A, Torres-Roca JF, Grass GD, Kim S, Latifi K, Hunt D, Johnstone PAS, Yamoah K. Proof-of-principle Phase I results of combining nivolumab with brachytherapy and external beam radiation therapy for Grade Group 5 prostate cancer: safety, feasibility, and exploratory analysis. Prostate Cancer P D. 2020 Jul. Pubmedid: 32651467.
  • Rubino S, Kim Y, Zhou J, Dhillon J, Li R, Spiess P, Poch M, Manley BJ, Pow-Sang J, Gilbert S, Sexton W, Zhang J. Positive Ki-67 and PD-L1 expression in post-neoadjuvant chemotherapy muscle-invasive bladder cancer is associated with shorter overall survival: a retrospective study. World J Urol. 2020 Jul. Pubmedid: 32656671.
  • O'Donnell PH, Arkenau HT, Sridhar SS, Ong M, Drakaki A, Spira AI, Zhang J, Gordon MS, Degboe AN, Gupta AK, Mukhopadhyay P, Huang W, Abdullah SE, Angra N, Roskos LK, Guo X, Friedlander T. Patient-reported outcomes and inflammatory biomarkers in patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab in phase 1/2 dose-escalation study 1108. Cancer. 2020 Jan.126(2):432-443. Pubmedid: 31581306.
  • Rosenberg J, Sridhar SS, Zhang J, Smith D, Ruether D, Flaig TW, Baranda J, Lang J, Plimack ER, Sangha R, Heath EI, Merchan J, Quinn DI, Srinivas S, Milowsky M, Wu C, Gartner EM, Zuo P, Melhem-Bertrandt A, Petrylak DP. EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. J Clin Oncol. 2020 Feb.38(10):1041-1049. Pubmedid: 32031899. Pmcid: PMC7106979.
  • Abida W, Campbell D, Patnaik A, Shapiro JD, Sautois B, Vogelzang NJ, Voog EG, Bryce AH, McDermott R, Ricci F, Rowe J, Zhang J, Piulats JM, Fizazi K, Merseburger AS, Higano CS, Krieger LE, Ryan CJ, Feng FY, Simmons AD, Loehr A, Despain D, Dowson M, Green F, Watkins SP, Golsorkhi T, Chowdhury S. Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: Analysis From the Phase II TRITON2 Study. Clin Cancer Res. 2020 Feb.26(11):2487-2496. Pubmedid: 32086346.
  • Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, Sautois B, Vogelzang NJ, Bambury RM, Voog E, Zhang J, Piulats JM, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Higano CS, Krieger LE, Sternberg CN, Watkins SP, Despain D, Simmons AD, Loehr A, Dowson M, Golsorkhi T, Chowdhury S. Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. J Clin Oncol. 2020 Aug.38(32):3763-3772. Pubmedid: 32795228. Pmcid: PMC7655021.
  • West J, You L, Zhang J, Gatenby RA, Brown JS, Newton PK, Anderson ARA. Towards Multidrug Adaptive Therapy. Cancer Res. 2020 Apr.80(7):1578-1589. Pubmedid: 31948939. Pmcid: PMC7307613.
  • Brady-Nicholls R, Nagy JD, Gerke TA, Zhang T, Wang AZ, Zhang J, Gatenby RA, Enderling H. Prostate-specific antigen dynamics predict individual responses to intermittent androgen deprivation. Nat Commun. 2020 Apr.11(1):1750. Pubmedid: 32273504. Pmcid: PMC7145869.
  • West JB, Dinh MN, Brown JS, Zhang J, Anderson AR, Gatenby RA. Multidrug Cancer Therapy in Metastatic Castrate-Resistant Prostate Cancer: An Evolution-Based Strategy. Clin Cancer Res. 2019 Jul.25(14):4413-4421. Pubmedid: 30992299. Pmcid: PMC6665681.
  • Gatenby RA, Zhang J, Brown JS. First Strike-Second Strike Strategies in Metastatic Cancer: Lessons from the Evolutionary Dynamics of Extinction. Cancer Res. 2019 Jul.79(13):3174-3177. Pubmedid: 31221821. Pmcid: PMC6606376.
  • Yao J, Chen Y, Nguyen DT, Thompson ZJ, Eroshkin AM, Nerlakanti N, Patel AK, Agarwal N, Teer JK, Dhillon J, Coppola D, Zhang J, Perera R, Kim Y, Mahajan K. The Homeobox gene, HOXB13, Regulates a Mitotic Protein-Kinase Interaction Network in Metastatic Prostate Cancers. Sci Rep. 2019 Jul.9(1):9715. Pubmedid: 31273254. Pmcid: PMC6609629.
  • Chatzkel J, Mocha J, Smith J, Zhou JM, Kim Y, El-Haddad G, Zhang J. Circulating tumor cells and γH2AX as biomarkers for responsiveness to radium-223 in advanced prostate cancer patients. Future Sci OA. 2019 Dec.6(1):FSO437. Pubmedid: 31915536. Pmcid: PMC6920735.
  • Adashek JJ, Jain RK, Zhang J. Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer. Cells. 2019 Aug.8(8). Pubmedid: 31404966. Pmcid: PMC6721701.
  • Mei L, Zhang J, He K, Zhang J. Ataxia telangiectasia and Rad3-related inhibitors and cancer therapy: where we stand. J Hematol Oncol. 2019 Apr.12(1):43. Pubmedid: 31018854. Pmcid: PMC6482552.
  • Gupta S, Nordquist LT, Fleming MT, Berry WR, Zhang J, Ervin SL, Eisner JR, Baskin-Bey ES, Shore ND. Phase I Study of Seviteronel, a Selective CYP17 Lyase and Androgen Receptor Inhibitor, in Men with Castration-Resistant Prostate Cancer. Clin Cancer Res. 2018 Nov.24(21):5225-5232. Pubmedid: 30012563.
  • Peyton CC, Tang D, Reich RR, Azizi M, Chipollini J, Pow-Sang JM, Manley B, Spiess PE, Poch MA, Sexton WJ, Fishman M, Zhang J, Gilbert SM. Downstaging and Survival Outcomes Associated With Neoadjuvant Chemotherapy Regimens Among Patients Treated With Cystectomy for Muscle-Invasive Bladder Cancer. JAMA Oncol. 2018 Nov.4(11):1535-1542. Pubmedid: 30178038. Pmcid: PMC6248089.
  • Poch M, Hall M, Joerger A, Kodumudi K, Beatty M, Innamarato PP, Bunch BL, Fishman MN, Zhang J, Sexton WJ, Pow-Sang JM, Gilbert SM, Spiess PE, Dhillon J, Kelley L, Mullinax J, Sarnaik AA, Pilon-Thomas S. Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer. Oncoimmunology. 2018 Jul.7(9):e1476816. Pubmedid: 30228944. Pmcid: PMC6140546.
  • Nerlakanti N, Yao J, Nguyen DT, Patel AK, Eroshkin AM, Lawrence HR, Ayaz M, Kuenzi BM, Agarwal N, Chen Y, Gunawan S, Karim RM, Berndt N, Puskas J, Magliocco AM, Coppola D, Dhillon J, Zhang J, Shymalagovindarajan S, Rix U, Kim Y, Perera R, Lawrence NJ, Schonbrunn E, Mahajan K. Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain-Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer. Mol Cancer Ther. 2018 Dec.17(12):2796-2810. Pubmedid: 30242092. Pmcid: PMC6528782.
  • Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep.3(9):e172411. Pubmedid: 28817753. Pmcid: PMC5824288.
  • Zhang J, Cunningham JJ, Brown JS, Gatenby RA. Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer. Nat Commun. 2017 Nov.8(1):1816. Pubmedid: 29180633. Pmcid: PMC5703947.
  • You L, Brown JS, Thuijsman F, Cunningham JJ, Gatenby RA, Zhang J, Staňková K. Spatial vs. non-spatial eco-evolutionary dynamics in a tumor growth model. J Theor Biol. 2017 Dec.435:78-97. Pubmedid: 28870617.
  • Leone AR, Zargar-Shoshtari K, Diorio GJ, Sharma P, Boulware D, Gilbert SM, Powsang JM, Zhang J, Sexton WJ, Spiess PE, Poch MA. Neoadjuvant Chemotherapy in Elderly Patients With Bladder Cancer: Oncologic Outcomes From a Single Institution Experience. Clin Genitourin Cancer. 2017 Aug.15(4):e583-e589. Pubmedid: 28410909.
  • Zargar-Shoshtari K, Kongnyuy M, Sharma P, Fishman MN, Gilbert SM, Poch MA, Pow-Sang JM, Spiess PE, Zhang J, Sexton WJ. Clinical role of additional adjuvant chemotherapy in patients with locally advanced urothelial carcinoma following neoadjuvant chemotherapy and cystectomy. World J Urol. 2016 Nov.34(11):1567-1573. Pubmedid: 27072536.
  • Wu M, Seto E, Zhang J. E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells. Oncotarget. 2015 May.6(13):11252-11263. Pubmedid: 25816777. Pmcid: PMC4484454.
  • Wu M, Dickinson SI, Wang X, Zhang J. Expression and function of SIRT6 in muscle invasive urothelial carcinoma of the bladder. Int J Clin Exp Pathol. 2014 Sep.7(10):6504-6513. Pubmedid: 25400728. Pmcid: PMC4230126.
  • Wu M, Wang X, McGregor N, Pienta K, Zhang J. Dynamic regulation of Rad51 by E2F1 and p53 in prostate cancer cells upon drug-induced DNA damage under hypoxia. Mol Pharmacol. 2014 Jun.85(6):866-876. Pubmedid: 24627085. Pmcid: PMC4014666.
  • Liu JJ, Zhang J. Sequencing systemic therapies in metastatic castration-resistant prostate cancer. Cancer Control. 2013 Jul.20(3):181-187. Pubmedid: 23811702.
  • Henderson-Jackson E, Sexton W, Zhang J, Hakam A, Petrovskyy VS, Bui MM, Chuang ST. Cystic prostatic ductal adenocarcinoma: an unusual presentation and cytological diagnosis. Ann Clin Lab Sci. 2012.42(1):81-88. Pubmedid: 22371914.
  • Zhang J, Lee J, Urba S, Foster J, Worden F. A phase II trial evaluating weekly docetaxel and capecitabine in patients with metastatic or advanced, locally recurrent head and neck cancers. Cancer Invest. 2010 Nov.28(9):910-916. Pubmedid: 20590443.
  • Kang HG, Jenabi JM, Zhang J, Keshelava N, Shimada H, May WA, Ng T, Reynolds CP, Triche TJ, Sorensen PH. E-cadherin cell-cell adhesion in ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase. Cancer Res. 2007 Apr.67(7):3094-3105. Pubmedid: 17409416. Pmcid: PMC3906735.
  • Hu-Lieskovan S, Zhang J, Wu L, Shimada H, Schofield DE, Triche TJ. EWS-FLI1 fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewing's family of tumors. Cancer Res. 2005 Jun.65(11):4633-4644. Pubmedid: 15930281.
  • Zhang J, Hu S, Schofield DE, Sorensen PH, Triche TJ. Selective usage of D-Type cyclins by Ewing's tumors and rhabdomyosarcomas. Cancer Res. 2004 Sep.64(17):6026-6034. Pubmedid: 15342383.
  • Tsao JL, Zhang J, Salovaara R, Li ZH, Järvinen HJ, Mecklin JP, Aaltonen LA, Shibata D. Tracing cell fates in human colorectal tumors from somatic microsatellite mutations: evidence of adenomas with stem cell architecture. Am J Pathol. 1998 Oct.153(4):1189-1200. Pubmedid: 9777950. Pmcid: PMC1853055.
  • Zhang J. Poly (ADP-ribose) polymerase inhibitor: an evolving paradigm in the treatment of prostate cancer. Asian J Androl. 16(3):401-406. Pubmedid: 24589464. Pmcid: PMC4023365.