Location out of bounds
Radial
Radial

Directory

All Investigators
Ze Zheng, MBBS, PhD

Ze Zheng, MBBS, PhD

Assistant Investigator,
Assistant Professor

Thrombosis, Hemostasis & Vascular Biology

Assistant Professor of Medicine
Division of Endocrinology and Molecular Medicine
Medical College of Wisconsin

Education and training

Postdoctoral Training
Columbia University, Postdoc training, Molecular Medicine

Doctoral Training
Jiamusi University, MBBS, Clinical Medicine
Wayne State University, PhD, Molecular Biology & Genetics

Contact Us

Ze Zheng, MBBS, PhD

Assistant Investigator,
Assistant Professor
Email

  • Research Interests

    Our laboratory studies the interactions between metabolism and blood clot lysis. Fibrinolysis, the primary mechanism that dissolves a blood clot, is initiated by a serine protease tissue-type plasminogen activator (tPA). Our previous study discussed a novel source and regulation of endogenous basal plasma tPA derived from hepatocytes, which is important for fibrinolysis when a vessel injury occurs. The tPA activity is inhibited primarily by the serpin plasminogen activator inhibitor 1 (PAI-1). A balance between tPA and PAI-1 in plasma is essential for preventing excessive clotting. Our recent study revealed the mechanism of how hepatocytes sense metabolic stresses and imbalance the production of tPA and PAI-1, influencing the degree of impaired fibrinolysis in obesity.

    The goal of our laboratory is to understand the role of hepatocyte-derived tPA and basal fibrinolysis in hemostasis, and to develop diagnostic/ preventive/ therapeutic strategies that can be used to combat atherosclerosis, thrombosis, and bleeding disorders. Specific areas of research interests include: 1) a new link between reduced fibrinolysis and dyslipidemia, 2) circadian regulation of basal fibrinolysis and the morning onset of thrombotic events, 3) the role of hepatocyte tPA and liver injuries, 4) increased fibrinolysis in hemophilia, and 5) a timely study of fibrinolysis in COVID-19.

  • Grant Support
    • 2019-2022, ASH Scholar Award, American Society of Hematology
    • 2019-2022, AHA Career Development Award, American Heart Association
    • 2020-2021, COVID-19 Rapid Response Grant, Cardiovascular Center, Medical College of Wisconsin
  • Lab

    Research Technologist
    Hayley Lund

    Postdoctoral Fellow
    Wen Dai, MD

  • Publications
    1. Laing S, Wang G, Briazova T, Zhang C, Wang A, Zheng Z, Gow A, Chen AF, Rajagopalan S, Chen LC, Sun Q, Zhang K. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues. Am J Physiol Cell Physiol. 2010 Oct;299(4):C736-49. PMCID: PMC2957267
    2. Zhang C, Wang G, Zheng Z, Maddipati KR, Zhang X, Dyson G, Williams P, Duncan SA, Kaufman RJ, Zhang K. Endoplasmic reticulum-tethered transcription factor cAMP responsive element-binding protein, hepatocyte specific, regulates hepatic lipogenesis, fatty acid oxidation, and lipolysis upon metabolic stress in mice. Hepatology. 2012 Apr;55(4):1070-82. PMCID: PMC3319338
    3. Lee JS*, Zheng Z*, Mendez R, Ha SW, Xie Y, Zhang K. Pharmacologic ER stress induces non-alcoholic steatohepatitis in an animal model. Toxicol Lett. 2012 May 20;211(1):29-38. PMCID: PMC3334434. *Equal contributors
    4. Wang G, Liu G, Wang X, Sethi S, Ali-Fehmi R, Abrams J, Zheng Z, Zhang K, Ethier S, Yang ZQ. ERLIN2 promotes breast cancer cell survival by modulating endoplasmic reticulum stress pathways. BMC Cancer. 2012 Jun 08;12:225. PMCID: PMC3732090
    5. Zheng Z, Xu X, Zhang X, Wang A, Zhang C, Hüttemann M, Grossman LI, Chen LC, Rajagopalan S, Sun Q, Zhang K. Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model. J Hepatol. 2013 Jan;58(1):148-54. PMCID: PMC3527686
    6. Mendez R, Zheng Z, Fan Z, Rajagopalan S, Sun Q, Zhang K. Exposure to fine airborne particulate matter induces macrophage infiltration, unfolded protein response, and lipid deposition in white adipose tissue. Am J Transl Res. 2013;5(2):224-34. PMCID: PMC3612517
    7. Qiu Q, Zheng Z, Chang L, Zhao YS, Tan C, Dandekar A, Zhang Z, Lin Z, Gui M, Li X, Zhang T, Kong Q, Li H, Chen S, Chen A, Kaufman RJ, Yang WL, Lin HK, Zhang D, Perlman H, Thorp E, Zhang K, Fang D. Toll-like receptor-mediated IRE1α activation as a therapeutic target for inflammatory arthritis. EMBO J. 2013 Sep 11;32(18):2477-90. PMCID: PMC3770952
    8. Zheng Z*, Zhang C*, Yan J, Ruan Y*, Zhao X, San X, Mao Y, Sun Q, Zhang K, Fan Z. Diabetes mellitus is associated with hepatocellular carcinoma: a retrospective case-control study in hepatitis endemic area. PLoS One. 2013;8(12):e84776. PMCID: PMC3873428. *Equal contributors
    9. Kim H, Mendez R, Zheng Z, Chang L, Cai J, Zhang R, Zhang K. Liver-enriched transcription factor CREBH interacts with peroxisome proliferator-activated receptor α to regulate metabolic hormone FGF21. Endocrinology. 2014 Mar;155(3):769-82. PMCID: PMC3929740
    10. Zheng Z, Zhang X, Wang J, Dandekar A, Kim H, Qiu Y, Xu X, Cui Y, Wang A, Chen LC, Rajagopalan S, Sun Q, Zhang K. Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models. J Hepatol. 2015 Dec;63(6):1397-404. PMCID: PMC5003300
    11. Zhang X, Cai J, Zheng Z, Polin L, Lin Z, Dandekar A, Li L, Sun F, Finley RL, Fang D, Yang ZQ, Zhang K. A novel ER-microtubule-binding protein, ERLIN2, stabilizes Cyclin B1 and regulates cell cycle progression Cell Discovery. 8 September 2015;1.
    12. Zheng Z, Wang G, Li L, Tseng J, Sun F, Chen X, Chang L, Heng H, Zhang K. Transcriptional signatures of unfolded protein response implicate the limitation of animal models in pathophysiological studies. Environ Dis. 2016;1(1):24-30. PMCID: PMC5336312
    13. Ozcan L, Ghorpade DS, Zheng Z, de Souza JC, Chen K, Bessler M, Bagloo M, Schrope B, Pestell R, Tabas I. Hepatocyte DACH1 Is Increased in Obesity via Nuclear Exclusion of HDAC4 and Promotes Hepatic Insulin Resistance. Cell Rep. 2016 06 07;15(10):2214-2225. PMCID: PMC5068925
    14. Zheng Z*, Kim H*, Qiu Y, Chen X, Mendez R, Dandekar A, Zhang X, Zhang C, Liu AC, Yin L, Lin JD, Walker PD, Kapatos G, Zhang K. CREBH Couples Circadian Clock With Hepatic Lipid Metabolism. Diabetes. 2016 Nov;65(11):3369-3383. PMCID: PMC5079639. *Equal contributors
    15. Dandekar A, Qiu Y, Kim H, Wang J, Hou X, Zhang X, Zheng Z, Mendez R, Yu FS, Kumar A, Fang D, Sun F, Zhang K. Toll-like Receptor (TLR) Signaling Interacts with CREBH to Modulate High-density Lipoprotein (HDL) in Response to Bacterial Endotoxin. J Biol Chem. 2016 10 28;291(44):23149-23158. PMCID: PMC5087733
    16. Wang X, Zheng Z, Caviglia JM, Corey KE, Herfel TM, Cai B, Masia R, Chung RT, Lefkowitch JH, Schwabe RF, Tabas I. Hepatocyte TAZ/WWTR1 Promotes Inflammation and Fibrosis in Nonalcoholic Steatohepatitis. Cell Metab. 2016 12 13;24(6):848-862. PMCID: PMC5226184
    17. Kim H*, Zheng Z*, Walker PD, Kapatos G, Zhang K. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis. Mol Cell Biol. 2017 07 15;37(14). PMCID: PMC5492176. *Equal contributors
    18. Doran AC, Ozcan L, Cai B, Zheng Z, Fredman G, Rymond CC, Dorweiler B, Sluimer JC, Hsieh J, Kuriakose G, Tall AR, Tabas I. CAMKIIγ suppresses an efferocytosis pathway in macrophages and promotes atherosclerotic plaque necrosis. J Clin Invest. 2017 Nov 01;127(11):4075-4089. PMCID: PMC5663361
    19. Qiu Y, Zheng Z, Kim H, Yang Z, Zhang G, Shi X, Sun F, Peng C, Ding Y, Wang A, Chen LC, Rajagopalan S, Sun Q, Zhang K. Inhalation Exposure to PM2.5 Counteracts Hepatic Steatosis in Mice Fed High-fat Diet by Stimulating Hepatic Autophagy. Sci Rep. 2017 11 24;7(1):16286. PMCID: PMC5701159
    20. Ghorpade DS, Ozcan L, Zheng Z, Nicoloro SM, Shen Y, Chen E, Blüher M, Czech MP, Tabas I. Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance. Nature. 2018 03 29;555(7698):673-677. PMCID: PMC6021131
    21. Zheng Z#, Nayak L, Wang W, Yurdagul A Jr, Wang X, Cai B, Lapping S, Ozcan L, Ramakrishnan R, Pestell RG, Jain MK, Tabas I#. An ATF6-tPA pathway in hepatocytes contributes to systemic fibrinolysis and is repressed by DACH1. Blood. 2019 02 14;133(7):743-753. PMCID: PMC6376283. #Corresponding authors
    22. Cai B, Dongiovanni P, Corey KE, Wang X, Shmarakov IO, Zheng Z, Kasikara C, Davra V, Meroni M, Chung RT, Rothlin CV, Schwabe RF, Blaner WS, Birge RB, Valenti L, Tabas I. Macrophage MerTK Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis. Cell Metab. 2020 02 04;31(2):406-421.e7. PMCID: PMC7004886
    23. Yurdagul A Jr, Subramanian M, Wang X, Crown SB, Ilkayeva OR, Darville L, Kolluru GK, Rymond CC, Gerlach BD, Zheng Z, Kuriakose G, Kevil CG, Koomen JM, Cleveland JL, Muoio DM, Tabas I. Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury. Cell Metab. 2020 Mar 03;31(3):518-533.e10. PMCID: PMC7173557
    24. Wang X, Cai B, Yang X, Sonubi OO, Zheng Z, Ramakrishnan R, Shi H, Valenti L, Pajvani UB, Sandhu J, Infante RE, Radhakrishnan A, Covey DF, Guan KL, Buck J, Levin LR, Tontonoz P, Schwabe RF, Tabas I. Cholesterol Stabilizes TAZ in Hepatocytes to Promote Experimental Non-alcoholic Steatohepatitis. Cell Metab. 2020 May 05;31(5):969-986.e7. PMCID: PMC7313619
    25. Zheng Z#, Nakamura K, Gershbaum S, Wang X, Thomas S, Bessler M, Schrope B, Krikhely A, Liu RM, Ozcan L, López JA, Tabas I#. Interacting hepatic PAI-1/tPA gene regulatory pathways influence impaired fibrinolysis severity in obesity. J Clin Invest. 2020 Jul 13. #Corresponding authors
x

This website uses cookies to ensure you get the best experience on our website. Learn more