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Daohong Zhou, MD

Contact

210-450-3875

zhoud@uthscsa.edu

Departments & Divisions

Institutes & Centers

Research Areas

Cancer

Daohong Zhou, MD

Professor with Tenure, Biochemistry and Structural Biology

Associate Director for Drug Development of the Mays Cancer Center

Director of the Center for Innovative Drug Discovery (CIDD)

Dr. Daohong Zhou is a tenured professor in Department of Biochemistry & Structural Biology and a Joe R. and Terry Lozano Long Distinguished Chair of Developmental Therapeutics at the Long School of Medicine. Dr. Zhou also serves as the Director of the National Cancer Institute (NCI)- and Cancer Prevention and Research Institute of Texas (CPRIT)-funded Center of Innovative Drug Discovery (CIDD) and as the Associate Director for Drug Development at the NCI-designated Mays Cancer Center (MCC). Prior to joining UTHSA, he was a Professor in the Department of Pharmacodynamics at the College of Pharmacy and a Professor in the Department of Radiation Oncology at the College of Medicine, University of Florida (UF) at Gainesville and served as the Associate Director for Translation and Drug Development and the Henry E. Innes Endowed Professor of Cancer Research at the UF Health Cancer Center.

His research has led to a better understanding of the role of cellular senescence in ionizing radiation (IR) and chemotherapy induced normal tissue damage (such as bone marrow suppression and pulmonary fibrosis) and the discovery of the first potent and broad-spectrum senolytic agent, ABT263 (a dual Bcl-2 and Bcl-xl inhibitor), that can selectively kill senescent cells. This discovery may lead to new therapeutics for various age-related diseases and the side effects induced by chemotherapy and IR. More recently, he developed several proteolysis targeting chimeras (PROTACs) that can target Bcl-xl and other proteins of interest for degradation via the ubiquitination and proteasome system. He found that Bcl-xl PROTACs can selectively induce Bcl-xl degradation in senescent cells and various cancer cells but not in platelets, suggesting that Bcl-xl PROTACs have the potential to be developed as a better senolytic and anticancer agent than ABT263 by not causing thrombocytopenia. Importantly, Dr. Zhou’s efforts in the development of promising senolytics and cancer therapeutics has led to the FDA approval of DT2216, a Bcl-xl PROTAC, in phase I studies, and the founding of two biotechnology companies, Unity Biotechnology, which is publicly traded (UBX on NASDAQ, https://unitybiotechnology.com/) and Dialectic Therapeutics (https://www.dtsciences.com/), a Texas-based company that has received two CPRIT Awards for Product Development. Using the PROTAC drug development platform, he is developing additional specific antitumor and better senolytic agents.

Dr. Zhou has published more than 160 peer reviewed scientific articles and book chapters. His research has been well supported by grants from various private and government funding agencies, including NCI. Dr. Zhou serves on several national and international peer review panels and as a reviewer for various scientific publications. He was a regular member of the Radiation Therapeutics and Biology Study Section at the National Institutes of Health (NIH) and a Councilor of the Radiation Research Society (http://www.radres.org).

  • Professional Background

    Education

    • 1986 - MS - Immunology - Henan Medical University, Henan, China
    • 1982 - MD - Yunyang Medical College, Hubei, China

    Training

    • 1992 - Postdoctoral Training - Immunology - Johns Hopkins University, Baltimore, MD

    Highlights

    2022-               Long Distinguished Chair of Developmental Therapeutics, UTHSA

    2018-2022       Henry E. Innes Professorsip of Cancer Research, University of Florida

    2016                Established Investigator of Year Award, The Arkansas Biosciences Institute

    2010-2018       Arkansas Research Alliance Scholar, Arkansas Research Alliance

    2010-2018       The Winthrop Rockefeller Endowed Chair for Leukemia and Lymphoma Research, University of Arkansas for Medical Sciences

    Appointments

    • 1996-2000 - Assistant Professor - Department of Medicine, University of Kentucky, Lexington, KY
    • 200-2007 - Associate Professor - Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC
    • 2007-2010 - Professor - Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC
    • 2010-2018 - Professor - Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR
    • 2018-2022 - Professor - Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL
    • 2018-2022 - Professor - Department of Radiation Oncology, College of Medicine, UF, Gainesville, Gainesville, FL
    • 2022 - Professor - Department of Biochemistry & Structure Biology, College of Medicine, UTHSA, San Antonio, TX

  • Research & Grants

    Grants

    Title: Proteolysis-targeting chimera against BCL-XL inhibits breast cancer metastasis

    Project Number: R01 CA260239

    Name of PD/PI: Zhang, Zheng, & Zhou

    Source of Support: NIH/NCI

    Project/Proposal Start and End Date: 05/2021 – 04/2026           

     

    Title: Inhibition of Bcl-xL by Targeted Degradation

    Project Number: R01 CA241191

    Name of PD/PI: Zheng, Konopleva, & Zhou

    Source of Support: NIH/NCI

    Project/Proposal Start and End Date: 04/2020 – 03/2025           

     

    Title: Use of BCL-xL proteolysis targeting chimeras to treat pancreatic cancer

    Project Number: R01 CA242003

    Name of PD/PI: Zhou, Trevino, & Zheng

    Source of Support: NIH/NCI

    Project/Proposal Start and End Date: 09/2019 – 08/2024           

     

    Title: Develop BCL-xL proteolysis targeting chimeras as safer and better senolytics

    Project Number: R01 AG063801

    Name of PD/PI: Zhou, Elisseeff, & Zheng

    Source of Support: NIH/NIA

    Project/Proposal Start and End Date: 08/2019 – 03/2024           

     

    Title: Role of Senescent Cells in Radiation-induced Pulmonary Fibrosis

    Project Number: R01 CA219836

    Name of PD/PI: Zhou

    Source of Support: NIH/NCI

    Project/Proposal Start and End Date: 07/2017 – 07/2022           

     

    Title: Ionizing Radiation Induced Hematological Malignancies

    Project Number: R01 CA211963

    Name of PD/PI: Zhou

    Source of Support: NIH/NCI

    Project/Proposal Start and End Date: 04/2017 – 03/2022           

     

    Title: Intercollaborative Radiation Countermeasure (INTERACT) Consortium for Advanced Development of Medical Countermeasures to Mitigate/Treat Acute and Delayed Radiation Syndromes

    Project Number: U19 AI150574

    Name of PD/PI: Vujaskovic/Zhou-subaward PI

    Source of Support: NIH/NIAID

    Project/Proposal Start and End Date: 06/2020 – 05/2025           

     

    Title: Center for Innovative Drug Discovery: Enhancement of a Shared Cancer Resource for South Texas

    Project Number: RP160844

    Name of PD/PI: McHardy/Zhou-subaward PI

    Source of Support: CPRIT

    Project/Proposal Start and End Date: 09/2021 – 08/2026           

  • Service

    Institutional

    Associate Director for Drug Development of
    the Mays Cancer Center

    Director of the Center for Innovative Drug
    Discovery (CIDD)

  • Publications

      1. Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, Janakiraman K, Sharpless NE, Ding S, Feng W, Luo Y, Wang X, Aykin-Burns N, Krager K, Ponnappan U, Hauer-Jensen M, Meng A, Zhou D. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med. 22:78-83, 2016.
      2. Liu YL, Yan Y, Webster C, Shao L, Lensing SY, Ni H, Feng W, Colorado N, Pathak R, Xiang Z, Hauer-Jensen M, Li S, Zhou D, Emanuel PD. Timing of the loss of PTEN protein determines disease severity in a mouse model of myeloid malignancy. Blood. 127: 1912-22, 2016.
      3. Wang Y, Chang J, Liu X, Zhang X, Zhang S, Zhang X, Zhou D*, Zheng G*. Discovery of piperlongumine as a potential novel lead for the development of senolytic agents. Aging. 8: 2915-2926, 2016. * co-corresponding authors
      4. Demaria M, O'Leary MN, Chang J, Shao L, Liu S, Alimirah F, Koenig K, Le C, Mitin N, Deal AM, Alston S, Academia EC, Kilmarx S, Valdovinos A, Wang B, de Bruin A, Kennedy BK, Melov S, Zhou D, Sharpless NE, Muss H, Campisi J. Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discov. 7: 165-176, 2017.
      5. Kim H-N, Chang J, Shao L, Han L, Iyer S, Manolagas SC, O'Brien CA, Jilka RL, Zhou D, Almeida M. DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age. Aging Cell. 16:693-703, 2017.  
      6. Pan J, Li D, Xu Y, Zhang J, Wang Y, Chen M, Lin S, Huang L, Chung EJ, Citrin DE, Wang Y, Hauer-Jensen M, Zhou D*, Meng A*. Inhibition of Bcl-2/xl with ABT-263 selectively kills senescent Type II pneumocytes and reverses persistent pulmonary fibrosis induced by ionizing radiation in mice. Int J Radiat Oncol Biol Phys. 99: 353-361, 2017. * co-corresponding authors
      7. Luo Y, Shao L, Chang J, Feng W, Liu YL, Cottler-Fox MH, Emanuel PD, Hauer-Jensen M, Bernstein ID, Liu L, Chen X, Zhou J, Murray PJ, Zhou D. M1 and M2 macrophages differentially regulate hematopoietic stem cell self-renewal and ex vivo expansion. Blood Advances. 2: 859-870, 2018.
      8. Zhang X, Zhang S, Liu X, Wang Y, Chang J, Zhang X, Mackintosh SG, Tackett AJ, He Y, Lv D, Laberge R-M, Campisi J, Wang J, Zheng G, Zhou D. Oxidation resistance 1 is a novel senolytic target. Aging Cell. 15:e12780, 2018.   
      9. Shao L, Chang J, Feng W, Wang X, Williamson EA, Li Y, Schajnovitz A, Scadden D, Mortensen LJ, Lin CP, Li L, Paulson A, Downing J, Zhou D*, Hromas RA*. Hem-1 is required for transition of fetal liver hematopoiesis to the bone marrow. Nature Communications, 9: 2377, 2018. * co-corresponding authors
      10. Li W, He Y, Zhang R, Zheng G, Zhou D. The curcumin analog EF24 is a novel senolytic agent. Aging (Albany NY). 2019 Jan 28;11(2):771-782.
      11. Cho JJ, Xu Z, Parthasarathy U, Drashansky TT, Helm EY, Zuniga AN, Lorentsen KJ, Mansouri S, Cho JY, Edelmann MJ, Duong DM, Gehring T, Seeholzer T, Krappmann D, Uddin MN, Califano D, Wang RL, Jin L, Li H, Lv D, Zhou D, Zhou L, Avram D. Elimination of senescent osteoclast progenitors has no effect on the age-associated loss of bone mass in mice. Nat Commun. 2019 Feb 11;10(1):701.
      12. Patil P, Dong Q, Wang D, Chang J, Wiley C, Demaria M, Lee J, Kang J, Niedernhofer LJ, Robbins PD, Sowa G, Campisi J, Zhou D, Vo N. Systemic clearance of p16INK4a -positive senescent cells mitigates age-associated intervertebral disc degeneration. Aging Cell. 2019 Jun;18(3):e12927.
      13. Kim HN, Chang J, Iyer S, Han L, Campisi J, Manolagas SC, Zhou D, Almeida M. Elimination of senescent osteoclast progenitors has no effect on the age-associated loss of bone mass in mice. Aging Cell. 2019 Jun;18(3):e12923.
      14. Zhang X, Thummuri D, He Y, Liu X, Zhang P, Zhou D, Zheng G. Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL. Chem Commun (Camb). 2019 Dec 5;55(98):14765-14768.
      15. Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, Campisi J, Collado M, Evangelou K, Ferbeyre G, Gil J, Hara E, Krizhanovsky V, Jurk D, Maier AB, Narita M, Niedernhofer L, Passos JF, Robbins PD, Schmitt CA, Sedivy J, Vougas K, von Zglinicki T, Zhou D, Serrano M, Demaria M. Cellular Senescence: Defining a Path Forward. Cell. 2019 Oct 31;179(4):813-827. doi: 10.1016/j.cell.2019.10.005. Review.
      16. Khan S, Zhang X, Lv D, Zhang Q, He Y, Zhang P, Liu X, Thummuri D, Yuan Y, Wiegand JS, Pei J, Zhang W, Sharma A, McCurdy CR, Kuruvilla VM, Baran N, Ferrando AA, Kim Y-M, Rogojina A, J Houghton P, Huang G, Hromas R, Konopleva M, Zheng G*, and Zhou D*. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nat Med. 2019 Dec;25(12):1938-1947. * co-corresponding authors
      17. Zhang X, He Y, Zhang P, Budamagunta V, Lv D, Thummuri D, Yang Y, Pei J, Yuan Y, Zhou D*, Zheng G*. Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines. Eur J Med Chem. 2020 May 4;199:112397.
      18. He Y, Zhang X, Chang J, Kim HN, Zhang P, Wang Y, Khan S, Liu X, Zhang X, Lv D, Song L, Li W, Thummuri D, Yuan Y, Wiegand JS, Ortiz YT, Budamagunta V, Elisseeff JH, Campisi J, Almeida M, Zheng G*, Zhou D*. Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity. Nat Commun. 2020 Apr 24;11(1):1996. * co-corresponding authors
      19. He Y, Li W, Lv D, Zhang X, Zhang X, Ortiz YT, Budamagunta V, Campisi J, Zheng G, Zhou D. Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity. Aging Cell. 2020 Mar;19(3):e13117. 
      20. Liu X, Zhang X, Lv D, Yuan Y, Zheng G, Zhou D. Assays and technologies for developing proteolysis targeting chimera degraders. Future Med Chem. 2020 Jun;12(12):1155-1179.
      21. He Y, Khan S, Huo Z, Lv D, Zhang X, Liu X, Yuan Y, Hromas R, Xu M, Zheng G, Zhou D. Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies. J Hematol Oncol. 2020 Jul 27;13(1):103.
      22. He Y, Koch R, Budamagunta V, Zhang P, Zhang X, Khan S, Thummuri D, Ortiz YT, Zhang X, Lv D, Wiegand JS, Li W, Palmer AC, Zheng G, Weinstock DM, Zhou D. DT2216-a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas. J Hematol Oncol. 2020 Jul 16;13(1):95.
      23. Khan S, He Y, Zhang X, Yuan Y, Pu S, Kong Q, Zheng G, Zhou D. PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics. Oncogene. 2020 Jun;39(26):4909-4924.
      24. Acklin S, Zhang M, Du W, Zhao X, Plotkin M, Chang J, Campisi J, Zhou D*, Xia F*. Depletion of senescent-like neuronal cells alleviates cisplatin-induced peripheral neuropathy in mice. Sci Rep. 2020 Aug 25;10(1):14170. * co-corresponding authors
      25. Faust HJ, Zhang H, Han J, Wolf MT, Jeon OH, Sadtler K, Peña AN, Chung L, Maestas DR Jr, Tam AJ, Pardoll DM, Campisi J, Housseau F, Zhou D, Bingham CO 3rd, Elisseeff JH. IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis. J Clin Invest. 2020 Oct 1;130(10):5493-5507.
      26. Limzerwala JF, Jeganathan KB, Kloeber JA, Davies BA, Zhang C, Sturmlechner I, Zhong J, Velasco RF, Fields AP, Yuan Y, Baker DJ, Zhou D, Li H, Katzmann DJ & van Deursen JM. FoxM1 insufficiency hyperactivates Ect2–RhoA–mDia1 signaling to drive cancer. Nature Cancer  2020 Oct 12;1:1010–1024.
      27. Kang JW, Zhan Z, Ji G, Sang Y, Zhou D, Li Y, Feng H, Cheng T. PUMA facilitates EMI1-promoted cytoplasmic Rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells. Signal Transduct Target Ther, 2021 Mar 31;6(1):129.
      28. Kolb R, De U, Khan S, Luo Y, Kim MC, Yu H, Wu C, Mo J, Zhang X, Zhang P, Zhang X, Borcherding N, Koppel D, Fu YX, Zheng SG, Avram D, Zheng G, Zhou D*, Zhang W*. Proteolysis-targeting chimera against BCL-X L destroys tumor-infiltrating regulatory T cells. Nat Commun. 2021 Feb 24;12(1):1281. * co-corresponding author
      29. Prasanna PG, Citrin DE, Hildesheim J, Ahmed MM, Venkatachalam S, Riscuta G, Xi D, Zheng G, van Deursen J, Goronzy J, Kron SJ, Anscher MS, Sharpless NE, Campisi J, Brown SL, Niedernhofer LJ, O'Loghlen A, Georgakilas AG, Paris F, Gius D, Gewirtz DA, Schmitt CA, Abazeed ME, Kirkland JL, Richmond A, Romesser PB, Lowe SW, Gil J, Mendonca MS, Burma S, Zhou D, Coleman CN. Therapy-Induced Senescence: Opportunities to Improve Anti-Cancer Therapy. J Natl Cancer Inst. 113: 1285-1298, 2021
      30. Budamagunta V, Manohar-Sindhu S, Yang Y, He Y, Traktuev D, Foster TC, Zhou D. Senescence-associated hyper-activation to inflammatory stimuli in vitro. Aging, 2021 Aug 10;13(15):19088-19107 (A priority research and cover story publication)
      31. Pal P, Thummuri D, Lv D, Liu X, Zhang P, Hu W, Poddar S, Hua N, Khan S, Yuan Y, Zhang X, Zhou D*, Zheng G*. Discovery of a Novel BCL-XL PROTAC Degrader with Enhanced BCL-2 Inhibition. J Med Chem. 64: 14230-14246, 2021 * co-corresponding authors
      32. Kim MC, Borcherding N, Ahmed K, Voigt A, Vishwakarma A, Kolb R, Kluz P, Pandey G, De U, Drashansky T, Helm E, Zhang X, Gibson-Corley K, Klesney-Tait J, Zhu Y, Lu J, Lu Y, Huang X, Xiang H, Cheng J, Wang D, Wang Z, Tang J, Hu J, Wang Z, Liu H, Li M, Zhuang H, Avram D, Zhou D, Bacher R, Zheng SG, Wu X, Zakharia Y, Zhang W. CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells. Nature Commun. 12: 5764, 2021
      33. Thummuri D, Khan S, Underwood PW, Zhang P, Wiegand J, Zhang X, Budamagunta V, Sobh A, Tagmount A, Loguinov A, Riner AN, Akki AS, Williamson E, Hromas R, Vulpe C, Zheng G, Trevino JG, Zhou D. Overcoming Gemcitabine Resistance in Pancreatic Cancer Using the BCL-XL Specific Degrader DT2216. Mol Cancer Ther. 21: 184-192, 2011
      34. Lv D, Pal P, Liu X, Zhang P, Jia Y, Thummuri D, Zhang P, Hu W, Pei J, Zhang Q, Zhou S, Khan S, Zhang X, Hua N, Yang Q. Arango S, Zhang W, Nayak D, Olsen SK, Weintraub ST, Hromas R, Konopleva M, Yuan Y*, Zheng G*, Zhou D*. Generation of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity. Nat Commun. 12: 6896, 2021. * co-corresponding authors
      35. Principe DR, Xiong R, Li Y, Pham TND, Kamath SD, Dubrovskyi O, Ratia K, Huang F, Zhao J, Shen Z, Thummuri D, Zhou D, Underwood PW, Trevino J, Munshi HG, Thatcher GRJ, Rana A. XP-524 is a dual-BET/EP300 inhibitor that represses oncogenic KRAS and potentiates immune checkpoint inhibition in pancreatic cancer.  Proc Natl Acad Sci U S A. 119:e2116764119, 2022.
      36. Khan S*, Wiegand J, Zhang P, Hu W, Thummuri D, Budamagunta V, Hua N, Jin L, Allegra CJ, Kopetz SE, Zajac-Kaye M, Kaye FJ, Zheng G, Zhou D*. BCL-XL PROTAC degrader DT2216 synergizes with sotorasib in pre-clinical models of KRASG12C-mutated cancers. J Hematol Oncol. 15: 23, 2022. * co-corresponding authors