Long Zheng, M.D., Ph.D.

Professional Background

Dr. Zheng is Russell J. Eilers MD Endowed Professor and Department Chair of Pathology and Laboratory Medicine at The University of Kansas Medical Center. He completed his Medical Degree at Nanchang University, China and Ph.D. at University of Vienna, Austria. Following his residency in Pathology and fellowship in Transfusion Medicine and Hemostasis at Washington University in St. Louis, Missouri, Dr. Zheng took his first faculty position at the University of Pennsylvania, Philadelphia, PA where he quickly rose to the rank of Associate Professor with tenure. Dr. Zheng was then recruited to the University of Alabama at Birmingham where he served the Division Director of Laboratory Medicine and attended clinical service in Blood Banking/Transfusion Medicine and Coagulation. In early 2020, Dr. Zheng was named the Department Chair and Service Chief of Pathology and Laboratory Medicine at the University of Kansas Medical Center, Kansas City, Kansas.

Dr. Zheng's research has been focused on Biology of ADAMTS13 and Pathogenesis of Thrombotic Thrombocytopenic Purpura (TTP), a potentially fatal blood disorder. Dr. Zheng first cloned and reported complete cDNA and protein sequences of ADAMTS13. He and his research team have published more than 150 manuscripts in various high-profile journals and 6 highly-sought book chapters including Williams Hematology, Clinical Hematology and Principal of Critical Care, etc. Dr. Zheng has served for 6 years in the NIH grant review panel for Hemostasis, Thrombosis, and Blood Transfusion (HTBT). He also served an associate editor for Journal of Thrombosis and Haemostasis and continues to serve the associate (or section) editors in Archives of Pathology and Laboratory Medicine, Annals of Blood, Blood VTH, Journal of Clinical Medicine, and Journal of Clinical and Translational Pathology, etc. Dr. Zheng is a passionate teacher and he has mentored more than 40 trainees, including graduate students, postdoctoral fellows, physician scientists, and junior research faculty, etc. Most of them have gone on to establish their own successful academic career.

• MD, Medicine, Nanchang University, Nanchang, Jiangxi
• PhD, Mol. Cell Biology, University of Vienna, Vienna, Austria
• Residency, Pathology, Washington University , St. Louis , Missouri
• Clinical Fellowship, Transfusion Medicine and Hemostasis, Washington University, St. Louis, Missouri

• Medical Liscence , Kansas State Board of Healing Arts

Research

Overview

Dr. Zheng's laboratory has been focused on understanding the mechanism of normal and abnormal blood coagulation. Specifically, his team are investigating the pathogenesis of TTP and developing novel therapeutics for TTP. TTP is caused by severe deficiency of plasma ADAMTS13 activity, resulting from autoantibodies or mutations in ADAMTS13. ADAMTS13 is an important plasma metalloprotease that cleaves endothelium-derived ultra large von Willebrand factor (VWF). An inability to cleave these ultra large VWF multimers or strings leads to uncontrolled platelet agglutination and thrombus formation, resulting in thrombocytopenia, microangiopathic hemolytic anemia, and organ damage, a characteristic feature of TTP.

Dr. Zheng first identified and cloned ADAMTS13, which provides a novel avenue to study the mechanism of hemostasis and the disease TTP. Recombinant ADAMTS13 has been now approved by U.S. FDA for the treatment of hereditary TTP. Following are Dr. Zheng's current research projects, primarily supported by National Heart, Lung, and Blood Institute (NHLBI).
Project 1. To determine the structure and function relationship of ADAMTS13 enzyme
Project 2. To determine the cofactor-dependent regulation of ADAMTS13 function
Project 3. To determine the mechanism of autoantibody inhibition leading to immune TTP. Project 4. To determine the mechanism of allosteric regulation of ADAMTS13 activity
Project 5. To establish and characterize various animal models of TTP, including zebrafish, mice, and rats to better understand the potential environmental triggers or genetic abnormalities contributing to the onset and development of TTP.
Project 6. To determine the role of ADAMTS13 and VWF in placental development and pathogenesis of preeclampsia.

Dr. Zheng's laboratory employs various cutting-edge technologies, including molecular cloning, PCR, protein engineering, protein expression, and protein purification, as well as microfluidic shear-based assay or intra vital microscopic imaging to analyze real-time thrombus formation and leukocyte rolling, etc. Additionally, CRISP/Cas9, single B cell Ig or RNA seq, bioinformatics, hydrogen-deuterium exchange plus mass spectrometry, and CryoEM, etc. are all employed to further understand the pathogenic mechanism of TTP and other inflammatory and thrombotic disorders.

• Pathogenesis of thrombotic microangiopathies, NHLBI, PI

• Zheng, X., L, Vesely, S., K, Cataland, S., R, Coppo, P, Geldziler, B, Iorio, A, Matsumoto, M, Mustafa, R., A, Pai, M, Rock, G, Russell, L, Tarawneh, R, Valdes, J, Peyvandi, F. 2020. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura.. Journal of thrombosis and haemostasis : JTH, 18 (10), 2496-2502
• Zheng, Xinglong. 2021. The standard of care for immune thrombotic thrombocytopenic purpura today. J Thromb Haemost
• Zheng, Xinglong. 2022. ADAMTS13 protease or lack of von Willebrand factor protects irradiation and melanoma-induced thrombotic microangiopathy in zebrafish. J Thromb Haemost
• Zheng, Xinglong. 2022. Coagulation factor VII enhances the cleavage of VWF by ADAMTS13 invivo. Blood (144)
• Zheng, Xinglong., L. 2023. A novel mechanism underlying allosteric regulation of ADAMTS-13 revealed by hydrogen−deuterium exchange plus mass spectrometry. Research and Practice in Thrombosis and Haemostasis, 7 (1)
• Zheng, X. Long. 2024. Mechanism underlying severe deficiency of plasma ADAMTS13 activity in immune thrombotic thrombocytopenic purpura. J Thromb Haemost
• Zheng, X. Long. 2024. Targeting Neutrophil Extracellular Trap Accumulation under Flow in Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura. Blood Adv.
• Zheng, Xinglong, Halkidis, K, Meng, C, Liu, S, Mayne, L, Siegel, D., L, Zheng, X., L. 2024. Mechanistic Insight into Multiple Antibody Binding to ADAMTS13 in Immune Thrombotic Thrombocytopenic Purpura. Res Pract Thromb Haemost