Research

Overview

Dr. Zheng's laboratory has been interested in studying the mechanism of normal and abnormal blood coagulation, specifically the pathogenesis and novel therapeutics of immune thrombotic thrombocytopenic purpura (iTTP). Severe deficiency of plasma metalloprotease ADAMTS13 is the important cause of iTTP. ADAMTS13 cleaves endothelial von Willebrand factor (VWF), critical for normal hemostasis. An inability to cleave VWF results in uncontrolled platelet agglutination and thrombus formation throughout the body.

Following are Dr. Zheng's current research projects, which is primarily supported by National Heart, Lung, and Blood Institute.

1) Structure and function relationship of ADAMTS13 enzyme
2) Cofactor-dependent regulation of ADAMTS13 function
3) Single B cell Ig sequencing to identify human monoclonal antibodies from iTTP patients.
4) Mechanism underlying allosteric regulation and inhibition of ADAMTS13 activity
5) Animal models including zebrafish, mice, and rats for understanding the potential environmental triggers or genetic abnormalities in pathogenesis of iTTP.

The laboratory employs various cutting-edge technologies, including molecular cloning, PCR, protein engineering, expression, and purification, as well as microfluidic shear-based assay or intravital microscopic imaging to analyze thrombus formation, leukocyte rolling. Additionally, CRISP/Cas, single B cell Ig or RNA seq, bioinformatics, and CryoEM, etc. are employed to further understand the pathogenic mechanism of iTTP and other thrombotic disorders.

• Novel Therapeutics for Acquired Thrombotic Thrombocytopenic Purpura, NHLBI, PI

• Zheng, L, Abdelgawwad, M., S, Zhang, D, Xu, L, Wei, S, Cao, W, Zheng, X., L. 2020. Histone-induced thrombotic thrombocytopenic purpura in adamts13 ^-/- zebrafish depends on von Willebrand factor.. Haematologica, 105 (4), 1107-1119
• Sui, J, Lu, R, Halkidis, K, Kocher, N., K, Cao, W, Marques, M., B, Zheng, X., L. 2020. Plasma levels of S100A8/A9, histone/DNA complexes, and cell-free DNA predict adverse outcomes of immune thrombotic thrombocytopenic purpura.. Journal of thrombosis and haemostasis : JTH
• Lu, R, Sui, J, Zheng, X., L. 2020. Elevated plasma levels of syndecan-1 and soluble thrombomodulin predict adverse outcomes in thrombotic thrombocytopenic purpura.. Blood advances, 4 (21), 5378-5388
• Cao, W, Cao, W, Zhang, W, Zheng, X., L, Zhang, X., F. 2020. Factor VIII binding affects the mechanical unraveling of the A2 domain of von Willebrand factor.. Journal of thrombosis and haemostasis : JTH, 18 (9), 2169-2176
• Basu, M., K, Massicano, F, Yu, L, Halkidis, K, Pillai, V, Cao, W, Zheng, L, Zheng, X., L. 2020. Exome Sequencing Identifies Abnormalities in Glycosylation and ANKRD36C in Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura.. Thrombosis and haemostasis
• Zheng, L, Zhang, D, Cao, W, Song, W., C, Zheng, X., L. 2019. Synergistic effects of ADAMTS13 deficiency and complement activation in pathogenesis of thrombotic microangiopathy.. Blood, 134 (13), 1095-1105
• Sui, J, Cao, W, Halkidis, K, Abdelgawwad, M., S, Kocher, N., K, Guillory, B, Williams, L., A, Gangaraju, R, Marques, M., B, Zheng, X., L. 2019. Longitudinal assessments of plasma ADAMTS13 biomarkers predict recurrence of immune thrombotic thrombocytopenic purpura.. Blood advances, 3 (24), 4177-4186
• McDaniel, J., K, Abdelgawwad, M., S, Hargett, A, Renfrow, M., B, Bdeir, K, Cao, W., J, Cines, D., B, Long, XL. 2019. Human Netrophil Peptide-1 Inhibits Thrombus Formation Under Arterial Flow via Its Terminal Free Cysteine Thiols. Journal of Thrombosis and Haemostasis, 17, 596-606
• Kumar, M., A, Cao, W, Pham, H., P, Raju, D, Nawalinski, K, Maloney-Wilensky, E, Schuster, J, Zheng, X., L. 2019. Relative Deficiency of Plasma A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeats 13 Activity and Elevation of Human Neutrophil Peptides in Patients with Traumatic Brain Injury.. Journal of neurotrauma, 36 (2), 222-229