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Ze Zheng, MD, PhD

Ze Ze profile

Ze Zheng, MD, PhD

Investigator

Thrombosis and Hemostasis

Associate Professor
Department of Medicine
Division of Endocrinology and Molecular Medicine
Department of Physiology (Secondary)
Medical College of Wisconsin

Associate Director of Basic Science Research
Medical College of Wisconsin Cardiovascular Research Center

Education and training

Postdoctoral Training
Columbia University, Molecular Medicine (Mentor: Ira Tabas, MD, PhD)

Doctoral Training
Jiamusi University, MD, Clinical Medicine 
Wayne State University, PhD, Molecular Biology & Genetics (Mentor: Kezhong Zhang, PhD)

Contact Information
  • ZZheng@Versiti.org

    • Research Interests

    Our laboratory studies the interactions between lipoprotein 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 (Blood, 2019). 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 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 (JCI, 2020). 

    A new study from our lab, discovered a direct interaction between tPA and apoB, the scaffold protein of LDL and VLDL particles, reducing VLDL production from hepatocytes and lowering atherogenic apoB-lipoprotein cholesterol in circulation (Science, 2023). 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 in atherothrombosis, 2) fibrinolysis and lipoproteins in hemophilia, 3) the role of lipoprotein in platelet biology, 4) the role of hepatocyte tPA and liver injuries, and 5) a timely study of dyslipidemia and thrombosis in COVID-19.

    Grant Support
    • AHA Collaborative Sciences Award, American Heart Association.
    • R01HL163516, NIH/NHLBI
    • R01HL174609, NIH/NHLBI

    Lab
     

    Hayley Lund, BS

    Lab Manager

    Hayley received her Bachelor of Science Degree in Biology in 2002 from the University of Stevens Point, Wisconsin. While working in David Mattson’s lab her research focused on salt induced hypertension and its effects on the renal system. Hayley joined Dr. Zheng’s lab in August of 2020 eager to help continue research on thrombosis and atherosclerosis.

     

    Wen Dai, MD, PhD

    Research Scientist

    Wen received his medical degree from Xiangya Medical School, Central South University, China in 2013. He finished his master’s degree and clinical residency training in internal medicine in The Second Xiangya Hospital in China in 2016 and continued his PhD and Clinical fellowship training in cardiology. After two years research training in Columbia University Medical Center, he joined the Zheng laboratory in September 2020 with an interest in the role of hepatic tPA in atherothrombosis.

     

    Ziyu Zhang, MD

    Postdoctoral Fellow

    Ziyu received her medical degree from Xiangya Medical School, Central South University, China in 2017. She finished her clinical residency training in internal medicine at the Second Xiangya Hospital in 2019 and continued her clinical fellowship training in cardiology. With her research experience in lipoprotein metabolism and cardiovascular diseases, and interest in the link between cardiometabolic disorders and hemostasis, she joined the Zheng laboratory in July 2021 to study the role of hepatocyte tPA and fibrinolysis in hemophilia and hemostasis.

     

    Hortense Triniac, PhD

    Postdoctoral Fellow

    Hortense obtained her master’s degree in Integrative Biology and Physiology at Sorbonne Université (France) in 2019, and a master’s degree in Neuroscience at Université de Caen Normandie (France) in 2020. She then obtained a PhD in molecular and cellular neuroscience in 2023 during which she studied the modulation of autophagy in cortical neurons in the context of ischemic stroke, as well as the neuronal cleavage of the tissue-type plasminogen activator (tPA) thrombolytic agent. Dr. Triniac joined the Zheng laboratory in January 2024 to study the role of hepatocyte-derived tPA and fibrinolysis in hemostasis.

     

    Alexis Smith, PhD

    Postdoctoral Fellow

    Alexis has joined the Versiti Blood Research Institute and Medical College of Wisconsin in October 2024 as a postdoctoral research fellow with research interests in platelet biology and lipoproteins. Prior to joining VBRI and MCW, Smith completed her PhD work earlier this year at the University of Kentucky in the lab of Dr. Sidney Whiteheart where she studied platelet biology and function focusing specifically on SNARE regulation in platelet exocytosis. In Smith’s spare time, she loves to read and do yoga. She also loves spending time with her family and traveling to new places.

     

    Marjorie Kipp, BS

    Technician

    Marge received her Certification as Biotechnology Technician in 1996 followed by her BS in Business Management in 2006. She has been with the BRI since 2003. She currently supports five labs and manages animal colonies. When she’s not in the lab she enjoys spending time with her family and their dog Sadie. They enjoy camping, fishing and traveling.

     

    Mindy Kim, BA

    MSTP (MD PhD) Graduate Student

    Mindy double majored and received her bachelor’s degree in Sociology and Natural Sciences at Johns Hopkins University in 2019. She then moved to Philadelphia during her gap years to work at the Perelman School of Medicine in the lab of Dr. Mitchell Lazar, where she helped investigate genomic and transcriptomic regulation of nuclear receptors, such as the glucocorticoid receptor and peroxisome proliferator-activated receptor gamma (PPARγ). She is now in the MSTP program at MCW and is currently a graduate student. With interests in further elucidating the relationship between hepatocyte-derived tPA and various metabolic and immunologic processes, she has joined the lab of Dr. Ze Zheng in July 2023.

     

    Maya Vergara (Rodriguez), BS

    Post-bac Research Trainee, Research Technologist

    Maya graduated with a Bachelor of Science from Marquette University in 2023, majoring in Cognitive Science and minoring in Biological Sciences. During her summer 2021 internship in Zheng lab through the Diversity Summer Health-Related Research Education Program (DSHREP) at the Medical College of Wisconsin, she studied the impact of race and ethnicity on mortality in COVID-19 inpatients in Milwaukee. After the completion of this program, she continued to work in the Zheng lab as a Research Technologist starting in the fall of 2021. When she is not completing schoolwork or doing research, she loves to dance with the student organization she created, Ballet Folklorico of Marquette University.

    Publications

    Click Here for a full list of publications from Dr. Ze Zhang

    Selected Publications
    1. Rodriguez M, Zheng Z. Connecting impaired fibrinolysis and dyslipidemia. Res Pract Thromb Haemost. 2024 Apr 5;8(3):102394. doi: 10.1016/j.rpth.2024.102394. eCollection 2024 Mar. PMID: 38706781
    2. Kim M, Zheng Z. Walking the VLDL tightrope in cardiometabolic diseases. Trends Endocrinol Metab. 2024 Aug 26:S1043-2760(24)00201-7. doi: 10.1016/j.tem.2024.07.020. Online ahead of print. Review. PMID: 39191606
    3. Zhang Z, Rodriguez M, Zheng Z. Clot or Not? Reviewing the Reciprocal Regulation Between Lipids and Blood Clotting. Arterioscler Thromb Vasc Biol. 2024 Mar;44(3):533-544. doi: 10.1161/ATVBAHA.123.318286. Epub 2024 Jan 18. Review. PubMed PMID: 38235555; PubMed Central PMCID: PMC10922732
    4. Dai W, Castleberry M, Zheng Z. Tale of two systems: the intertwining duality of fibrinolysis and lipoprotein metabolism. J Thromb Haemost. 2023 Oct;21(10):2679-2696. doi: 10.1016/j.jtha.2023.08.004. Epub 2023 Aug 12. Review. PubMed PMID: 37579878; PubMed Central PMCID: PMC10599797.
    5. 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. Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes. Science. 2023 Sep;381(6661):eadh5207. doi: 10.1126/science.adh5207. Epub 2023 Sep 1. PubMed PMID: 37651538; PubMed Central PMCID: PMC10697821.
    6. 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. Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19. Res Pract Thromb Haemost. 2023 Aug;7(6):102164. doi: 10.1016/j.rpth.2023.102164. eCollection 2023 Aug. PubMed PMID: 37680312; PubMed Central PMCID: PMC10480648.
    7. 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. Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress. Res Pract Thromb Haemost. 2023 May;7(4):100193. doi: 10.1016/j.rpth.2023.100193. eCollection 2023 May. PubMed PMID: 37538494; PubMed Central PMCID: PMC10394567.
    8. Yin L, Zhou T, Zheng Z, Long X, Qiu H, Lu HS. Editorial: Women in cardiovascular therapeutics. Front Cardiovasc Med. 2023;10:1183427. doi: 10.3389/fcvm.2023.1183427. eCollection 2023. PubMed PMID: 37234374; PubMed Central PMCID: PMC10207329.
    9. Zheng Z, Mukhametova L, Boffa MB, Moore EE, Wolberg AS, Urano T, Kim PY. Assays to quantify fibrinolysis: strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis. J Thromb Haemost. 2023 Apr;21(4):1043-1054. doi: 10.1016/j.jtha.2023.01.008. Epub 2023 Jan 14. Review. PubMed PMID: 36759279; PubMed Central PMCID: PMC10109242.
    10. Puzyrenko A, Jacobs ER, Padilla N, Devine A, Aljadah M, Gantner BN, Pan AY, Lai S, Dai Q, Rubenstein JC, North PE, Simpson PM, Willoughby RE, O'Meara CC, Flinn MA, Lough JW, Ibrahim EH, Zheng Z, Sun Y, Felix J, Hunt BC, Ross G, Rui H, Benjamin IJ. Collagen-Specific HSP47(+) Myofibroblasts and CD163(+) Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS-CoV-2 Infections. J Am Heart Assoc. 2023 Feb 21;12(4):e027990. doi: 10.1161/JAHA.122.027990. Epub 2023 Feb 15. PubMed PMID: 36789856; PubMed Central PMCID: PMC10111490.
    11. Furon J, Yetim M, Pouettre E, Martinez de Lizarrondo S, Maubert E, Hommet Y, Lebouvier L, Zheng Z, Ali C, Vivien D. Blood tissue Plasminogen Activator (tPA) of liver origin contributes to neurovascular coupling involving brain endothelial N-Methyl-D-Aspartate (NMDA) receptors. Fluids Barriers CNS. 2023 Feb 3;20(1):11. doi: 10.1186/s12987-023-00411-w. PubMed PMID: 36737775; PubMed Central PMCID: PMC9896721.
    12. Shi H, Wang X, Li F, Gerlach BD, Yurdagul A Jr, Moore MP, Zeldin S, Zhang H, Cai B, Zheng Z, Valenti L, Tabas I. CD47-SIRPα axis blockade in NASH promotes necroptotic hepatocyte clearance by liver macrophages and decreases hepatic fibrosis. Sci Transl Med. 2022 Nov 23;14(672):eabp8309. doi: 10.1126/scitranslmed.abp8309. Epub 2022 Nov 23. PubMed PMID: 36417485; PubMed Central PMCID: PMC10199725.
    13. Zheng Z, Riva N, Scarlatescu E, de Moerloose P, Ariëns R, Amigo MC; ISTH Ethics Committee. Developing and improving the ethical framework for the ISTH. J Thromb Haemost. 2022 Aug;20(8):1753-1754. doi: 10.1111/jth.15780. PMID: 35859283
    14. Rodriguez M, Dai W, Lund H, Osinski K, Zhang Z, Silverstein R, Zheng Z. The correlations among racial/ethnic groups, hypertriglyceridemia, thrombosis, and mortality in hospitalized patients with COVID-19. Best Pract Res Clin Haematol. 2022 Sep;35(3):101386. doi: 10.1016/j.beha.2022.101386. Epub 2022 Oct 3. PMID: 36494155
    15. Nayak L, Zheng Z. COVID-19: A hematological perspective. Best Pract Res Clin Haematol. 2022 Sep;35(3):101412. doi: 10.1016/j.beha.2022.101412. Epub 2022 Nov 4. PubMed PMID: 36494151; PubMed Central PMCID: PMC9633637.
    16. Dai W, Lund H, Chen Y, Zhang J, Osinski K, Jones SZ, Kreuziger LB, López JA, Benjamin IJ, Silverstein RL, Zheng Z. Hypertriglyceridemia during hospitalization independently associates with mortality in patients with COVID-19. J Clin Lipidol. 2021 Sep-Oct;15(5):724-731. doi: 10.1016/j.jacl.2021.08.002. Epub 2021 Aug 10. PMID: 34470719
    17. 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 Aug 3;130(8):4348-4359. doi: 10.1172/JCI135919. PMID: 32657780
    18. 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 Feb 14;133(7):743-753. doi: 10.1182/blood-2018-07-864843. Epub 2018 Dec 1. PMID: 30504459

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