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 Researcher
Hortense Triniac, PhD
Postdoctoral Researcher
Ziyu Zhang, MD
Postdoctoral Researcher
Marjorie Kipp, BS
Technician
Mark Castleberry, PhD
Research Scientist I
Mindy Kim, BA
MSTP Student
Maya Rodriguez
Student Research Assistant
Research in the Ze Zheng Laboratory
Recent Publications
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Regulation of hepatic inclusions and fibrinogen biogenesis by SEL1L-HRD1 ERAD.
(Song Z, Thepsuwan P, Hur WS, Torres M, Wu SA, Wei X, Tushi NJ, Wei J, Ferraresso F, Paton AW, Paton JC, Zheng Z, Zhang K, Fang D, Kastrup CJ, Jaiman S, Flick MJ, Sun S.) Nat Commun. 2024 Oct 26;15(1):9244 PMID: 39455574 PMCID: PMC11512042 SCOPUS ID: 2-s2.0-85207624408 10/26/2024
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Walking the VLDL tightrope in cardiometabolic diseases.
(Kim M, Zheng Z.) Trends Endocrinol Metab. 2024 Aug 26 PMID: 39191606 08/28/2024
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Oxidized LDL regulates efferocytosis through the CD36-PKM2-mtROS pathway.
(Zhang J, Chang J, Chen V, Beg MA, Huang W, Vick L, Wang Y, Zhang H, Yttre E, Gupta A, Castleberry M, Zhang Z, Dai W, Song S, Zhu J, Yang M, Brown AK, Xu Z, Ma YQ, Smith BC, Zielonka J, Traylor JG, Dhaou CB, Orr AW, Cui W, Zheng Z, Chen Y.) bioRxiv. 2024 Jul 15 PMID: 39071358 PMCID: PMC11275753 07/29/2024
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Connecting impaired fibrinolysis and dyslipidemia.
(Rodriguez M, Zheng Z.) Res Pract Thromb Haemost. 2024 Mar;8(3):102394 PMID: 38706781 PMCID: PMC11066549 05/06/2024
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Clot or Not? Reviewing the Reciprocal Regulation Between Lipids and Blood Clotting.
(Zhang Z, Rodriguez M, Zheng Z.) Arterioscler Thromb Vasc Biol. 2024 Mar;44(3):533-544 PMID: 38235555 PMCID: PMC10922732 SCOPUS ID: 2-s2.0-85185252234 01/18/2024
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Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity.
(Sim MMS, Mollica MY, Alfar HR, Hollifield M, Chung DW, Fu X, Gandhapudi S, Coenen DM, Prakhya KS, Mahmood DFD, Banerjee M, Peng C, Li X, Thornton AC, Porterfield JZ, Sturgill JL, Sievert GA, Barton-Baxter M, Zheng Z, Campbell KS, Woodward JG, López JA, Whiteheart SW, Garvy BA, Wood JP.) bioRxiv. 2024 Feb 09 PMID: 38370737 PMCID: PMC10871343 02/19/2024
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(Chen V, Zhang J, Chang J, Beg MA, Vick L, Wang D, Gupta A, Wang Y, Zhang Z, Dai W, Kim M, Song S, Pereira D, Zheng Z, Sodhi K, Shapiro JI, Silverstein RL, Malarkannan S, Chen Y.) Front Cardiovasc Med. 2024;11:1436865 PMID: 39156133 PMCID: PMC11327822 SCOPUS ID: 2-s2.0-85201434395 08/19/2024
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Tale of two systems: the intertwining duality of fibrinolysis and lipoprotein metabolism.
(Dai W, Castleberry M, Zheng Z.) J Thromb Haemost. 2023 Oct;21(10):2679-2696 PMID: 37579878 PMCID: PMC10599797 SCOPUS ID: 2-s2.0-85171457835 08/15/2023
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Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.
(Dai W, Zhang H, Lund H, Zhang Z, Castleberry M, Rodriguez M, Kuriakose G, Gupta S, Lewandowska M, Powers HR, Valmiki S, Zhu J, Shapiro AD, Hussain MM, López JA, Sorci-Thomas MG, Silverstein RL, Ginsberg HN, Sahoo D, Tabas I, Zheng Z.) Science. 2023 Sep;381(6661):eadh5207 PMID: 37651538 PMCID: PMC10697821 SCOPUS ID: 2-s2.0-85169348601 08/31/2023
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(Zhang Z, Dai W, Zhu W, Rodriguez M, Lund H, Xia Y, Chen Y, Rau M, Schneider EA, Graham MB, Jobe S, Wang D, Cui W, Wen R, Whiteheart SW, Wood JP, Silverstein R, Berger JS, Kreuziger LB, Barrett TJ, Zheng Z.) Res Pract Thromb Haemost. 2023 Aug;7(6):102164 PMID: 37680312 PMCID: PMC10480648 09/08/2023
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Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress.
(Kahn SR, Arnold DM, Casari C, Desch KC, Devreese KMJ, Favaloro EJ, Gaertner F, Gouw SC, Gresele P, Griffioen AW, Heger L, Kini RM, Kohli S, Leader A, Lisman T, Lordkipanidzé M, Mullins E, Okoye HC, Rosovsky RP, Salles-Crawley II, Selby R, Sholzberg M, Stegner D, Violi F, Weyand AC, Williams S, Zheng Z.) Res Pract Thromb Haemost. 2023 May;7(4):100193 PMID: 37538494 PMCID: PMC10394567 08/04/2023
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Editorial: Women in cardiovascular therapeutics.
(Yin L, Zhou T, Zheng Z, Long X, Qiu H, Lu HS.) Front Cardiovasc Med. 2023;10:1183427 PMID: 37234374 PMCID: PMC10207329 05/26/2023