Zheng Laboratory
Lab Director | Ze Zheng, MBBS, PhD
- Assistant Professor, Division of Endocrinology and Molecular Medicine, Department of Medicine (primary), Medical College of Wisconsin
- Assistant Associate Investigator, Versiti Blood Research Institute, Blood Center of Wisconsin
- Member, Cardiovascular Center, Medical College of Wisconsin
- Assistant Professor, Department of Physiology (secondary), Medical College of Wisconsin
Research Areas
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.
Current Members
Hayley Lund, BS
Lab Manager
Wen Dai, MD
Postdoctoral Fellow
Ziyu Zhang, MD
Postdoctoral Fellow
Marjorie Kipp, BS
Technician
Mark Castleberry, PhD
Research Scientist
Maya Rodriguez
Student Research Assistant
Research in the Ze Zheng Laboratory
Recent Publications
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Developing and improving the ethical framework for the ISTH.
(Zheng Z, Riva N, Scarlatescu E, de Moerloose P, Ariëns R, Amigo MC, ISTH Ethics Committee.) J Thromb Haemost. 2022 Aug;20(8):1753-1754 PMID: 35859283 07/22/2022
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Impact of COVID-19 on Hematology-Oncology Trainees: A Quantitative and Qualitative Assessment.
(Durani U, Major A, Velazquez AI, May J, Nelson M, Zheng Z, Hall AG, Alam ST, Reynolds R, Thompson JC, Kumbamu A, Das DG, Murphy MC, Henry E, Lee AI, Marshall AL, Wun T, Weeks LD.) JCO Oncol Pract. 2022 Apr;18(4):e586-e599 PMID: 34990292 PMCID: PMC9014488 SCOPUS ID: 2-s2.0-85128487414 01/07/2022
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Deficiency of macrophage PHACTR1 impairs efferocytosis and promotes atherosclerotic plaque necrosis.
(Kasikara C, Schilperoort M, Gerlach B, Xue C, Wang X, Zheng Z, Kuriakose G, Dorweiler B, Zhang H, Fredman G, Saleheen D, Reilly MP, Tabas I.) J Clin Invest. 2021 Apr 15;131(8) PMID: 33630758 PMCID: PMC8262505 SCOPUS ID: 2-s2.0-85104174793 02/26/2021
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(Dai W, Lund H, Chen Y, Zhang J, Osinski K, Jones SZ, Kreuziger LB, López JA, Benjamin IJ, Silverstein RL, Zheng Z.) J Clin Lipidol. 2021;15(5):724-731 PMID: 34470719 PMCID: PMC8353976 SCOPUS ID: 2-s2.0-85114047849 09/03/2021
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(Zheng Z, Nakamura K, Gershbaum S, Wang X, Thomas S, Bessler M, Schrope B, Krikhely A, Liu RM, Ozcan L, López JA, Tabas I.) J Clin Invest. 2020 Aug 03;130(8):4348-4359 PMID: 32657780 PMCID: PMC7410057 SCOPUS ID: 2-s2.0-85089125237 07/14/2020
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Cholesterol Stabilizes TAZ in Hepatocytes to Promote Experimental Non-alcoholic Steatohepatitis.
(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.) Cell Metab. 2020 May 05;31(5):969-986.e7 PMID: 32259482 PMCID: PMC7313619 SCOPUS ID: 2-s2.0-85083861208 04/08/2020
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(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.) Cell Metab. 2020 Mar 03;31(3):518-533.e10 PMID: 32004476 PMCID: PMC7173557 SCOPUS ID: 2-s2.0-85080068507 02/01/2020
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Macrophage MerTK Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis.
(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.) Cell Metab. 2020 Feb 04;31(2):406-421.e7 PMID: 31839486 PMCID: PMC7004886 SCOPUS ID: 2-s2.0-85078479595 12/17/2019
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An ATF6-tPA pathway in hepatocytes contributes to systemic fibrinolysis and is repressed by DACH1.
(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.) Blood. 2019 Feb 14;133(7):743-753 PMID: 30504459 PMCID: PMC6376283 SCOPUS ID: 2-s2.0-85061475922 12/07/2018
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Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance.
(Ghorpade DS, Ozcan L, Zheng Z, Nicoloro SM, Shen Y, Chen E, Blüher M, Czech MP, Tabas I.) Nature. 2018 Mar 29;555(7698):673-677 PMID: 29562231 PMCID: PMC6021131 SCOPUS ID: 2-s2.0-85044788933 03/22/2018
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(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.) Sci Rep. 2017 Nov 24;7(1):16286 PMID: 29176715 PMCID: PMC5701159 SCOPUS ID: 2-s2.0-85034992166 11/28/2017
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Interaction between stress responses and circadian metabolism in metabolic disease.
(Yang Z, Kim H, Ali A, Zheng Z, Zhang K.) Liver Res. 2017 Sep;1(3):156-162 PMID: 29430321 PMCID: PMC5805151 SCOPUS ID: 2-s2.0-85051645629 02/13/2018