Our lab investigates the mechanisms by which platelets, clotting  factors, and vascular cells interact to drive thrombosis, inflammation, and vascular remodeling. We combine genetic tools, in vivo disease models, molecular and cellular approaches to identify mechanisms that can be targeted therapeutically. Current research focus areas include:

1. Platelet Disorders and Thromboinflammation
   We investigate the molecular mechanisms that regulate platelet production, function, and pathological activation in inherited platelet disorders and thromboinflammatory diseases. Using ANKRD26-associated thrombocytopenia as a model of inherited platelet dysfunction, we examine how genetic alterations disrupt megakaryocyte development, platelet production and function, and may contribute to increased susceptibility to hematologic malignancies. We also investigate how platelets transition from hemostatic cells to drivers of thromboinflammation, with a focus on NINJ1-mediated platelet membrane disruption and proinflammatory signaling that promote microvascular thrombosis and tissue injury.
2. Thrombosis and Vascular Remodeling
   We investigate how dysregulation of the ADAMTS13–VWF axis and platelet activation drives thrombus formation, vascular inflammation, and pathological vascular remodeling. Using experimental models of acute pulmonary embolism (APE) and chronic thromboembolic pulmonary hypertension (CTEPH), we examine how abnormal VWF–platelet interactions and platelet-derived mediators contribute to thrombus persistence, endothelial dysfunction, and progressive pulmonary vascular remodeling. These studies aim to define the molecular mechanisms linking thrombosis to vascular remodeling and identify novel therapeutic targets for thromboembolic and pulmonary vascular diseases.

Hiromasa Kawashima, M.D.,Ph.D., Visiting researcher 

Nihal Modugu, B.A./M.D. student, KEE learner 

• Wu Z, Dong H, Zhang Q, Chai Z, Li A, Dominguez EM, Zhao X, Spikes L, Soares MJ, Long Zheng X, Zheng L. Targeting pathogenic VWF/ADAMTS13 dysregulation attenuates CTEPH progression. bioRxiv. 2026 Jun 22;. doi: 10.64898/2026.06.17.732997. PubMed PMID: 42395503; PubMed Central PMCID: PMC13320736.
• Zhang Q, Zheng L*, Chai Z, Wu Z, Dominguez EM, Soares MJ, Zheng XL. Rat models of thrombotic thrombocytopenic purpura reveal crucial role of placental ADAMTS13 in perinatal survival. Blood Adv. 2026 May 26;10(10):3615-3628. doi: 10.1182/bloodadvances.2026019661. PubMed PMID: 41915891; PubMed Central PMCID: PMC13207463.
• Zheng L, Wu Z, Yada N, Liu S, Lin C, Bignotti A, Zhao X, Zheng XL. Modeling ANKRD26 5'-UTR mutation-related thrombocytopenia. Dis Model Mech. 2025 Apr 1;18(4). doi: 10.1242/dmm.052222. Epub 2025 Apr 28. PubMed PMID: 40170493; PubMed Central PMCID: PMC12067082.
• Zheng L, Adili R, Wu Z, Zhang Q, Zhu G, Lei X, Liu Z, Neves MAD, Ma W, Slavkovic S, Xu XR, Ni H, Zheng XL. Preventative and therapeutic effects of a novel humanized anti-glycoprotein Ibα fragment of antigen-binding region in a murine model of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2025 May;23(5):1596-1607. doi: 10.1016/j.jtha.2025.02.009. Epub 2025 Feb 15. PubMed PMID: 39956431; PubMed Central PMCID: PMC13155645.
• Liu J, Zheng L. Microplastic migration and transformation pathways and exposure health risks. Environ Pollut. 2025 Mar 1;368:125700. doi: 10.1016/j.envpol.2025.125700. Epub 2025 Jan 15. Review. PubMed PMID: 39824338.
• Wu Z, Chen SY, Zheng L. Sulforaphane Attenuates Ethanol-Induced Teratogenesis and Dysangiogenesis in Zebrafish Embryos. Int J Mol Sci. 2024 Oct 27;25(21). doi: 10.3390/ijms252111529. PubMed PMID: 39519082; PubMed Central PMCID: PMC11546994.
• Yada N, Zhang Q, Bignotti A, Gralnek SH, Sosnovske D, Hogan K, Ye Z, Zheng L, Zheng XL. Targeting neutrophil extracellular trap accumulation under flow in patients with immune-mediated thrombotic thrombocytopenic purpura. Blood Adv. 2024 May 28;8(10):2536-2551. PubMed PMID: 38513079; PubMed Central PMCID: PMC11131081.
• Zheng L, Zheng XL. Animal models for thrombotic thrombocytopenic purpura: a narrative review. Ann Blood. 2023 Sep 30;8. doi: 10.21037/aob-22-18. Epub 2022 Nov 16. PubMed PMID: 39148951; PubMed Central PMCID: PMC11326488.
• Zheng L, Hill J, Zheng L, Rumi MAK, Zheng XL. A Simple, Robust, and Cost-effective Method for Genotyping Small-scale Mutations. J Clin Transl Pathol. 2022;2(3):108-115. doi: 10.14218/JCTP.2022.00014. Epub 2022 Sep 14. PubMed PMID: 36276172; PubMed Central PMCID: PMC9585490.
• Zheng L, Cao L, Zheng XL. ADAMTS13 protease or lack of von Willebrand factor protects irradiation and melanoma-induced thrombotic microangiopathy in zebrafish. J Thromb Haemost. 2022 Oct;20(10):2270-2283. doi: 10.1111/jth.15820. Epub 2022 Aug 7. PubMed PMID: 35894519; PubMed Central PMCID: PMC9641623.
• Zheng L, Abdelgawwad MS, Zhang D, Xu L, Wei S, Cao W, Zheng XL. Histone-induced thrombotic thrombocytopenic purpura in adamts13 (-/-) zebrafish depends on von Willebrand factor. Haematologica. 2020 Apr;105(4):1107-1119. doi: 10.3324/haematol.2019.237396. Epub 2019 Nov 21. PubMed PMID: 31753928; PubMed Central PMCID: PMC7109750.
• Zheng L, Zhang D, Cao W, Song WC, Zheng XL. Synergistic effects of ADAMTS13 deficiency and complement activation in pathogenesis of thrombotic microangiopathy. Blood. 2019 Sep 26;134(13):1095-1105. doi: 10.1182/blood.2019001040. Epub 2019 Aug 13. PubMed PMID: 31409673; PubMed Central PMCID: PMC6764266.
• Zheng L, Mao Y, Abdelgawwad MS, Kocher NK, Li M, Dai X, Li B, Zheng XL. Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpura. Blood Adv. 2016 Nov 29;1(1):75-83. doi: 10.1182/bloodadvances.2016000711. PubMed PMID: 28480350; PubMed Central PMCID: PMC5419690.