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Faculty Detail    
Name X. LONG ZHENG
Robert B. Adams Endowed Professor of Pathology
Director of Laboratory Medicine
Attending Physician in Transfusion Medicine
Associate Editor, Journal of Thrombosis and Haemostasis
Section Editor, Archives of Pathology and Laboratory Medicine
 
Campus Address WP P230 Zip 7331
Phone  205-975-8160
E-mail  xzheng@uabmc.edu
Other websites 1. UAB TTP Research Group
2. TTP Foundation Award
3. A possible novel therapy for TTP
4. NIH grant supports TTP research
5. Dr. Zander Received ASH Congressional Fellowship
6. Dr. McDaniel won the HTRS mentored award
7. Dr. Zheng speaks at 9th BIC International Conference, Rome, Italy on TTP
8. Dr. Zheng shares the Research Innovation in Scientific Excellence (RISE) Award from AABB
9. A novel therapy for immune-mediated TTP
     

Education
Medical School  Nanchang University, Nanchang, China       M.D. 
Residency  Huazhong University of Science and Technology, Wuhan, China       Obstetrics and Gynecology 
Graduate  Medical University of Vienna, Vienna, Austria     1994  Ph.D. 
Residency  Washington University School of Medicine, St. Louis, Missouri     2002  Clinical Pathology 
Fellowship  Washington University School of Medicine, St. Louis, Missouri     2003  Transfusion Medicine/Hemostasis 

Certifications
Board Certificate, American Board of Pathology  2003-Current 
Board Certificate, American Board of Blood Banking/Transfusion Medicine  2003-Current 
Medical License, Commonwealth of Pennsylvania  2003-Current 
Medical License, State of New Jersey  2008-Current 
Medical License, State of Alabama  2014-Current 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Laboratory Medicine Professor
Secondary  Medicine  Med - Hematology & Oncology Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Immunology 
Integrative Genetics Graduate Program 
Medical Scientist Training Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Zheng received his M.D. from Nanchang University, Nanchang, China and Ph.D. from the Medical University of Vienna, Austria. He then completed his postdoctoral fellowship (1995-1999) with Dr. J. Evan Sadler at the Howard Hughes Medicine Institute, Washington University in St. Louis, residency in Laboratory Medicine (1999-2002) and clinical fellowship (2002-2003) in Transfusion Medicine/Blood Banking in Washington University in St. Louis, Missouri. Dr. Zheng is board-certified in Clinical Pathology and Transfusion Medicine/Blood Banking from American Board of Pathology. Dr. Zheng was appointed in 2003 as an Assistant Professor and rose to the rank of Associate Professor with tenure in 2011 in the Department of Pathology, the University of Pennsylvania, Philadelphia, PA. Additionally, he was the Director of Hematology and Coagulation Laboratories at the Children's Hospital of Philadelphia. Dr. Zheng joined the University of Alabama at Birmingham in February 2015 as Robert B. Adams Professor of Pathology and Division Director of Laboratory Medicine, Department of Pathology. Dr. Zheng has been a NIH R01-sponsored principal investigator since 2003 and has published more than 90 manuscripts in high impact and peer-reviewed journals. He has received many prestigious awards including the Karl Link New Investigator Award from ATVB, the Established Investigator Award from American Heart Association, the Gift of Life from Ree Wynn Foundation and Claude P. Brown Memorial Lecturer from American Association of Clinical Science. Dr. Zheng is a member of AASS, ASH, AHA, ASGCT, ISTH, AABB, and ACLPS, etc. Also, Dr. Zheng serves as the Associate Editors for the Journal of Thrombosis and Haemostasis and Archives Pathology & Laboratory Medicine.

Society Memberships
Organization Name Position Held Org Link
     
Academy of Clinical Laboratory Physician Scientists (ACLPS)  Member (since 1999)  http://www.aclps.org/index.html 
American Heart Association (AHA)  Member (since 2008)  http://www.aha.org 
American Society for Hematology (ASH)  Member (since 1995)  http://www.hematology.org 
American Society of Gene and Cell Therapy (ASGCT)  Member (since 2008)  http://www.asgct.org 
American Society of Hematology (ASH)  Vice Chair (2014) and Chair (2015) for SC-Hemostasis  http://www.hematology.org 
Archives Pathology & Laboratory Medicine   Section Editor  http://www.archivesofpathology.org 
Arteriosclerosis, Thrombosis and Vascular Biology (ATVB)  Council Member (since 2008)  http://atvb.ahajournals.org 
International Society of Thrombosis and Hemostasis (ISTH)   Member (since 2003)  https://www.isth.org 
Journal of Thrombosis and Haemostasis  Associate Editor  http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1538-7836 



Research/Clinical Interest
Title
Molecular Mechanisms of Normal and Abnormal Blood Clotting; Inflammation and Microvascular Thrombosis; CRISPR/Cas9 Gene Editing as a Novel Therapeutic Strategy for Thrombotic Diseases
Description
Dr. Zheng's laboratory is interested in understanding the mechanisms of normal and abnormal blood coagulation, inflammation, and vascular biology. In particular, he and his colleagues focus on elucidating the pathogenesis of thrombotic thrombocytopenic purpura (TTP), a potentially fatal syndrome. Deficiency of plasma ADAMTS13 metalloprotease is the primary cause. ADAMTS13 is an enzyme that cleaves von Willebrand factor (VWF), an adhesion protein that helps agglutinate platelets for hemostasis. Deficiency of this enzyme leads to exaggerated platelet agglutination and the formation of microvascular thrombosis throughout the body, resulting in death. Current treatment is whole body plasma exchange. Dr. Zheng was among the first group of investigators who first discovered and cloned ADAMTS13 protease. In the past decade, Dr. Zheng's lab has made major contribution in determining the structure-function relationship and cofactor-dependent regulation of ADAMTS13. His lab is committed to develop novel tools for diagnosis and treatment of TTP. Potential rotation projects for graduate students include: a) Structure-function relationship of ADAMTS13; b) cofactor-dependent regulation of ADAMTS13 function; c) novel assay development for diagnosis of TTP; d) the role of systemic inflammation in pathogenesis of TTP; e) AAV-mediated gene therapy for hereditary and acquired TTP. Techniques in molecular biology, biochemistry/biophysics, and cell biology, as well as animal models are all commonly used in the laboratory. Current personnel: Wendy Cao, MD, PhD, Instructor; Vikram Pillai, PhD, Postdoctoral fellow; Liang Zheng, PhD, Postdoctoral fellow; Elizabeth M Staley, MD, PhD, Instructor; Mohammad Abdelgawwd, M.D., MS, graduate student, and Nicole Kocher, BS, research technician.

Selected Publications 
Publication PUBMEDID
Abdelgawwad M, Cao W, Zheng L, Kocher NK, Williams LA, and Zheng XL. Transfusion of Platelets Loaded With Recombinant ADAMTS13 (A Disintegrin and Metalloprotease With Thrombospondin Type 1 Repeats-13) Is Efficacious for Inhibiting Arterial Thrombosis Associated with Thrombotic Thrombocytopenic Puprura. 2018 Nov;38(11):2731-2743. doi: 10.1161/ATVBAHA.118.311407.  30354235 
Staley EM, Cao W, Pham HP, Kim CH, Kocher NK, Zheng L, Gangaraju R, Lorenz RG, Williams LA, Marques MB, Zheng XL. Clinical factors and biomarkers predicting outcome in patients with immune-mediated thrombotic thrombocytopenic purpura. Haematologica. 2018 Aug 31. pii: haematol.2018.198275. doi: 10.3324/haematol.2018.198275.   30171022  
Kumar MA, Cao W, Pham HP, Raju D, Nawalinski K, Maloney-Wilensky E, Schuster J, and Zheng XL. Relative Deficiency of Plasma ADAMTS13 Activity and Elevation of Human Neutrophil Peptides in Patients with Traumatic Brain Injury. J Neurotruma. 2018 Aug 14. doi: 10.1089/neu.2018.5696.  29848170 
Russell RT, McDaniel JK, Cao WJ, Shroyer M, Wagener BM, Zheng XL (corr. au.) and Pittet JF. Low Plasma ADAMTS13 Activity is Associated with Coagulopathy, Endothelial Cell Damage and Mortality after Severe Pediatric Trauma. Thromb Haemost. 2018 Apr;118(4):676-687. doi: 10.1055/s-0038-1636528.   29618154 
Joly BS, Zheng XL and Veyradier A. Understanding thrombotic microangiopathies in children. Inten. Care Med., 2018 Sep;44(9):1536-1538. doi: 10.1007/s00134-018-5059-2.   29368057 
Staley EM, Simmons SC, Feldman AZ, Lorenz RG, Marques MB, Williams LA 3rd, Zheng XL, Pham HP. Management of chronic myeloid leukemia in the setting of pregnancy: when is leukocytapheresis appropriate? A case report and review of the literature. Transfusion. 2018 Feb;58(2):456-460. doi: 10.1111/trf.14448.  29230832 
Ping Z., A. Soni, L.A. Williams III, H.P. Pham, M.K. Base, and X.L. Zheng. Mutations in Coagulation Factor VIII Are Associated with More Favorable Outcome in Patients with Cutaneous Melanoma. TH Open 2017 Jul;1(2):e113-e121.  29152610 
Xiao J, Feng Y, Li X, Li W, Fan L, Liu J, Zeng X, Chen K, Chen X, Zhou X, Zheng XL (corr. au.), and Chen S. Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development. Arterioscler Thromb Vasc Biol. 2017 Sep;37(9):1748-1756.  28751574 
Saha M, McDanniel J, and Zheng XL. Pathogenesis, Diagnosis, And Potential Novel Therapeutics for Thrombotic Thrombocytopenic Purpurpa. J. Thromb. Haemost. 2017 Oct;15(10):1889-1900.  28662310 
Kim CH, Simmons SC, Williams Iii LA, Staley EM, Zheng XL, Pham HP. ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis. Transfusion. 2017 Nov;57(11):2609-2618.  28646526 
Kumar M, Cao WJ, McDaniel JK, Pham HP, Raju D, Nawalinski K, Frangos S, Kung S, Zager E, Kasner SE, Levine JM, Zheng XL. Plasma ADAMTS13 activity and von Willebrand factor antigen and activity in patients with subarachnoid hemorrhage. Thromb. Haemost. 2017; 117(4):691-699.  28102428 
Ueda Y, Mohammed I, Song D, Gullipalli D, Zhou L, Sato S, Wang Y, Gupta S, Cheng Z, Wang H, Bao J, Mao Y, Brass L, Zheng XL, Miwa T, Palmer M, Dunaief J, Song WC. Murine systemic thrombophilia and hemolytic uremic syndrome from a factor H point mutation. Blood. 2017; 129(9):1184-1196.  28057640 
Nguyen GN, George LA, Siner JI, Davidson RJ, Zander CB, Zheng XL, Arruda VR, Camire RM, Sabatino DE. Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia A. J Thromb Haemost. 2017;15(1):110-121.  27749002 
Cao WJ, and Zheng XL. Conformational quiescence of ADAMTS13 prevents proteolytic promiscuity: comment. J Thromb Haemost. 2017;15(3):586-589.   28055145 
Williams III LA, Drwiega JC, Cao W, Pham HP, Bertoli LF, and Zheng XL. Acquired autoimmune thrombotic thrombocytopenic purpura in a case of severe hemophilia A. Haemophilia. 2016; 22(6):e565-e567.   27704646 
Zheng L, Mao Y, Abdelgawwad MS, Kocher NK, Li M, Dai X, Li B, and Zheng XL. Therapeutic Efficacy of Platelet Glycoprotein Ib Antagonist Anfibatide in Murine Models of Thrombotic Thrombocytopenia Purpura. Blood Adv. 2016 1:75-83.  28480350 
Cao W, Pham HP, Williams LA, McDaniel J, Siniard RC, Lorenz RG, Marques MB, Zheng XL. Human Neutrophil Peptides And Complement Factor Bb In Pathogenesis Of Acquired Thrombotic Thrombocytopenic Purpura. Haematologica. 2016; 101(11):1319-1326.  27662014  
Pillar V.G., Bao J., Zander C.B., McDaniel J.K., Chetty P.S., Seeholzer S.H., Bdeir K., Cines D.B., Zheng X.L. Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTP. Blood. 2016;28(1):110-9.  27207796 
Ostertag EM, Kacir S, Thiboutot M, Gulendran G, Zheng XL, Cines DB, Siegel DL. ADAMTS13 autoantibodies cloned from patients with acquired thrombotic thrombocytopenic purpura: 1. Structural and functional characterization in vitro. Transfusion. 2016;56(7):1763-74.  27040144 
Ostertag EM, Bdeir K, Kacir S, Thiboutot M, Gulendran G, Yunk L, Hayes VM, Motto DG, Poncz M, Zheng XL, Cines DB, Siegel DL. ADAMTS13 autoantibodies cloned from patients with acquired thrombotic thrombocytopenic purpura: 2. Pathogenicity in an animal model. Transfusion. 2016;56(7):1775-85.  27040023 
Tutwiler V, Madeeva D, Ahn HS, Andrianova I, Hayes V, Zheng XL, Cines DB, McKenzie SE, Poncz M, Rauova L. Platelet transactivation by monocytes promotes the prothrombotic state in heparin-induced thrombocytopenia. Blood. 2016;127(4):464-72  26518435 
Casina VC, Hu W, Mao JH, Lu RN, Hanby HA, Picken B, Kan ZY, Lim WK, Mayne L, Ostertag EM, Kacir S, Siegel DL, Englander SW, and Zheng XL. High resolution epitope mapping by HX MS reveals the pathogenic mechanism and a possible therapy for autoimmune TTP syndrome. Proc Natl Acad Sci USA. 2015;112:9620-5.  26203127  
Zander CB, Cao W, Zheng XL. ADAMTS13 and von Willebrand factor interaction. Curr Opin Hematol. 2015;22:452-9.  26186678 
Zheng XL. ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura. Annu Rev Med. 2015; 66: 211-25.   25587650 
Pickens B, Mao Y, Li D, Siegel DL, Poncz M, Cines DB, and Zheng XL. Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents murine models of thrombotic thrombocytopenic purpura. Blood. 2015;125 (21):3326-34.  25800050 
Zheng XL. ADAMTS13, lucky to have a hydrophobic pocket. Blood. 2015;125 (12):1852-3.  25792731 
Lu RN, Yang S, Wu HM, Zheng XL. Unconjugated Bilirubin Inhibits Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Protease. J Thromb Haemost. 2015;13(6):1064-72.  25782102 
Bauer RC, Tohyama J, Cui J, Cheng L, Yang J, Zhang X, Ou K, Paschos GK, Zheng XL, Parmacek MS, Rader DJ, Reilly MP. Knockout of Adamts7, A Novel CAD Locus in Humans, Reduces Atherosclerosis in Mice. Circulation. 2015;131(13):1202-13.  25712206 
Zheng XL. DNase, ADAMTS13, and iPAD4: good for the heart. Blood. 2014;123:10-1.   24385497 
Grillberger R, Casina VC, Turecek PL, Zheng XL, Rottensteiner H, Scheiflinger F. Anti-ADAMTS13 IgG autoantibodies present in healthy individuals share linear epitopes with those in patients with thrombotic thrombocytopenic purpura. Haematologica. 2014;99:e58-60.   24532042 
Chen J, Zhou H, Diacovo A, Zheng XL, Emsley J, Diacovo TG. Exploiting the kinetic interplay between GPIb-VWF binding interfaces to regulate hemostasis and thrombosis. Blood. 2014;124:3799-807.  25293780 
Bao J, Xiao J, Mao Y, Zheng XL. Carboxyl terminus of ADAMTS13 directly inhibits platelet aggregation and ultra large von Willebrand factor string formation under flow in a free-thiol-dependent manner. Arterioscler Thromb Vasc Biol. 2014;34:397-407.  24357063 
Skipwith CG, Haberichter SL, Gehrand A, Zheng XL. Compromised shear-dependent cleavage of type 2N von Willebrand factor variants by ADAMTS13 in the presence of factor VIII. Thromb Haemost. 2013;110:202-4.   23636243 
Jin SY, Xiao J, Bao J, Zhou S, Wright JF, Zheng XL. AAV-mediated expression of an ADAMTS13 variant prevents shigatoxin-induced thrombotic thrombocytopenic purpura. Blood. 2013;121:3825-9,  23515928 
Cao W, Sabatino DE, Altynova E, Lange AM, Casina VC, Camire RM, Zheng XL. Light chain of factor VIII is sufficient for accelerating cleavage of von Willebrand factor by ADAMTS13 metalloprotease. J Biol Chem. 2012;287:32459-66  22854959 
Jin SY, Tohyama J, Bauer RC, Cao NN, Rader DJ, Zheng XL. Genetic ablation of Adamts13 gene dramatically accelerates the formation of early atherosclerosis in a murine model. Arterioscler Thromb Vasc Biol. 2012;32:1817-23.  22652598 
Zheng XL. ADAMTS13 meets MR, then what? Blood. 2012;119:3652-4.  22517873 
Wroblewska A, van Haren SD, Herczenik E, Kaijen P, Ruminska A, Jin SY, Zheng XL, van den Biggelaar M, ten Brinke A, Meijer AB, Voorberg J. Modification of an exposed loop in the C1 domain reduces immune responses to factor VIII in hemophilia A mice. Blood. 2012;119:5294-300.  22498747 
Jian C, Xiao J, Gong L, Skipwith CG, Jin SY, Kwaan HC, Zheng XL. Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura. Blood. 2012;119:3836-43.  22289888  
Xiao J, Jin SY, Xue J, Sorvillo N, Voorberg J, Zheng XL. Essential domains of a disintegrin and metalloprotease with thrombospondin type 1 repeats-13 metalloprotease required for modulation of arterial thrombosis. Arterioscler Thromb Vasc Biol. 2011;31:2261-9.  21799176 
Jobes D, Wolfe Y, O'Neill D, Calder J, Jones L, Sesok-Pizzini D, Zheng XL. Toward a definition of "fresh" whole blood: an in vitro characterization of coagulation properties in refrigerated whole blood for transfusion. Transfusion. 2011;51:43-51.  20663116 
Skipwith CG, Cao W, Zheng XL. Factor VIII and platelets synergistically accelerate cleavage of von Willebrand factor by ADAMTS13 under fluid shear stress. J Biol Chem. 2010;285:28596-603.   20605782 
Zheng XL, Wu HM, Shang D, Falls E, Skipwith CG, Cataland SR, Bennett CL, Kwaan HC. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura. Haematologica. 2010;95:1555-62.  20378566 
Jin SY, Skipwith CG, Zheng XL. Amino acid residues Arg(659), Arg(660), and Tyr(661) in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factor. Blood. 2010;115:2300-10.  20075158 
Raife TJ, Cao W, Atkinson BS, Bedell B, Montgomery RR, Lentz SR, Johnson GF, Zheng XL. Leukocyte proteases cleave von Willebrand factor at or near the ADAMTS13 cleavage site. Blood. 2009;114:1666-74.  19541819 
Laje P, Shang D, Cao W, Niiya M, Endo M, Radu A, DeRogatis N, Scheiflinger F, Zoltick PW, Flake AW, Zheng XL. Correction of murine ADAMTS13 deficiency by hematopoietic progenitor cell-mediated gene therapy. Blood. 2009;113:2172-80.  19141866 

Keywords
ADAMTS13, von Willebrand factor, TTP, Arterial thrombosis, Vascular biology, Autoimmunity, and Inflammation, CRISPR/Cas9 Gene Editing