Positions

Overview

  • I am the Robert B. Adams Endowed Professor of Pathology and Division Director of Laboratory Medicine, Department of Pathology at the University of Alabama at Birmingham (UAB). I completed my Medical degree in Nanchang, China and Ph.D. in Mol. Cell. Biology at University of Vienna, Austria. Following my residency in Clinical Pathology and fellowship in Transfusion Medicine (Blood banking and Hemostasis) at Barnes-Jewish Hospital, Washington University in St. Louis, Missouri, I took my first faculty position as Assistant Professor and Director of Coagulation Laboratory at the Children’s Hospital of Philadelphia, affiliated with University of Pennsylvania, Philadelphia, PA. I rose to the rank of Tenured Associate Professor of Pathology in 2011. In Feb 2015, I was recruited to the University of Alabama at Birmingham.

    My passion has been in providing high-quality patient care, supporting education, and fostering innovative research. At CHOP/Penn, I helped build one of the most innovative and advanced coagulation laboratory to support patient care, education, and cutting edge research. At UAB, I am leading a team to implement various innovative processes to improve the quality of service and help build a high complexity laboratory with automation. I am the first scientist who first identified and cloned ADAMTS13, a plasma metalloprotease critical for hemostasis; deficiency of this enzymatic activity results in a potentially fatal syndrome thrombotic thrombocytopenic purpura (TTP). My laboratory has focused on the structure-function and regulation of ADAMTS13, as well as pathogenesis and novel therapeutics of immune TTP. My colleagues and I have published more than 100 manuscripts in high-profile and peer reviewed journals. Additionally, I serve the NIH study section, associate editors for two important journals in our field: Journal of Thrombosis and Haemostasis and Archives of Pathology and Laboratory Medicine.

    I enjoy music, outdoor hiking, and fishing, as well as seeing the world.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 Histone-induced thrombotic thrombocytopenic purpura in adamts13-/- zebrafish depends on von Willebrand factor.Haematologica2019
    2019 Synergistic effects of ADAMTS13 deficiency and complement activation in pathogenesis of thrombotic microangiopathyBlood.  134:1095-1105. 2019
    2019 Apolipoprotein B100/Low-Density Lipoprotein Regulates Proteolysis and Functions of von Willebrand Factor under Arterial Shear.Thromb Haemost2019
    2019 Human neutrophil peptide-1 inhibits thrombus formation under arterial flow via its terminal free cysteine thiolsJournal of Thrombosis and Haemostasis.  17:596-606. 2019
    2019 Validation and cost-effectiveness of an in-house dithiothreitol (DTT)treatment protocol for daratumumab patients in a large tertiary care hospital provides gateway for implementation in smaller community hospitalsTransfusion and Apheresis Science.  58:152-155. 2019
    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 InjuryJournal of Neurotrauma.  36:222-229. 2019
    2019 Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpuraHaematologica.  104:166-175. 2019
    2019 Identification of cysteine thiol-based linkages in ADAMTS13 in support of a non-proteolytic regulation of von Willebrand factorJournal of Thrombosis and Haemostasis2019
    2018 Understanding thrombotic microangiopathies in childrenIntensive Care Medicine.  44:1536-1538. 2018
    2018 Low Plasma ADAMTS13 Activity Is Associated with Coagulopathy, Endothelial Cell Damage and Mortality after Severe Paediatric TraumaThrombosis and Haemostasis.  118:676-687. 2018
    2018 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 purpuraArteriosclerosis, Thrombosis, and Vascular Biology.  38:2731-2743. 2018
    2017 ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysisTransfusion.  57:2609-2618. 2017
    2017 Plasma levels of complement activation fragments C3b and sC5b-9 significantly increased in patients with thrombotic microangiopathy after allogeneic stem cell transplantationAnnals of Hematology.  96:1849-1855. 2017
    2017 Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeuticsJournal of Thrombosis and Haemostasis.  15:1889-1900. 2017
    2017 Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta DevelopmentArteriosclerosis, Thrombosis, and Vascular Biology.  37:1748-1756. 2017
    2017 Mutations in Coagulation Factor VIII Are Associated with More Favorable Outcome in Patients with Cutaneous Melanoma.TH Open.  1:e113-e121. 2017
    2017 Murine systemic thrombophilia and hemolytic uremic syndrome from a factor H point mutationBlood.  129:1184-1196. 2017
    2017 Conformational quiescence of ADAMTS-13 prevents proteolytic promiscuity: commentJournal of Thrombosis and Haemostasis.  15:586-589. 2017
    2017 Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia AJournal of Thrombosis and Haemostasis.  15:110-121. 2017
    2017 Plasma ADAMTS13 activity and von Willebrand factor antigen and activity in patients with subarachnoid haemorrhageThrombosis and Haemostasis.  117:691-699. 2017
    2016 Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpura.Blood Advances.  1:75-83. 2016
    2016 Acquired autoimmune thrombotic thrombocytopenic purpura in a case of severe haemophilia AHaemophilia.  22:e565-e567. 2016
    2016 Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpuraHaematologica.  101:1319-1326. 2016
    2016 Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: A potential link of inflammation to TTPBlood.  128:110-119. 2016
    2016 ADAMTS13 autoantibodies cloned from patients with acquired thrombotic thrombocytopenic purpura: 1. Structural and functional characterization in vitroTransfusion.  56:1763-1774. 2016
    2016 ADAMTS13 autoantibodies cloned from patients with acquired thrombotic thrombocytopenic purpura: 2. Pathogenicity in an animal modelTransfusion.  56:1775-1785. 2016
    2016 Platelet transactivation by monocytes promotes thrombosis in heparin-induced thrombocytopeniaBlood.  127:464-472. 2016
    2016 Human neutrophil peptides inhibit cleavage of von Willebrand factor by ADAMTS13: a potential link of inflammation to TTPBlood.  blood-2015. 2016
    2016 Therapeutic efficacy of the platelet glycoprotein Ib antagonist anfibatide in murine models of thrombotic thrombocytopenic purpuraBlood Advances 2016 1:75-83; doi:10.1182/bloodadvances.20160007112016
    2015 High-resolution epitope mapping by HX MS reveals the pathogenic mechanism and a possible therapy for autoimmune TTP syndromeProceedings of the National Academy of Sciences.  112:9620-9625. 2015
    2015 ADAMTS13 and von Willebrand factor interactionsCurrent Opinion in Hematology.  22:452-459. 2015
    2015 ADAMTS13, lucky to have a hydrophobic pocketBlood.  125:1852-1853. 2015
    2015 ADAMTS13 and its variants promote angiogenesis via upregulation of VEGF and VEGFR2Cellular and Molecular Life Sciences.  72:349-356. 2015
    2015 ADAMTS13 and von willebrand factor in thrombotic thrombocytopenic purpuraAnnual Review of Medicine.  66:211-225. 2015
    2015 Knockout of Adamts7, a novel coronary artery disease locus in humans, reduces atherosclerosis in miceCirculation.  131:1202-1213. 2015
    2015 Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents thrombotic thrombocytopenic purpura in murine modelsBlood.  125:3326-3334. 2015
    2015 Unconjugated bilirubin inhibits proteolytic cleavage of von Willebrand factor by ADAMTS13 proteaseJournal of Thrombosis and Haemostasis.  13:1064-1072. 2015
    2014 Exploiting the kinetic interplay between GPIbα-VWF binding interfaces to regulate hemostasis and thrombosisBlood.  124:3799-3807. 2014
    2014 Research advances on ADAM28 expression and ADAM28-mediated tumor metastasisZhongguo Shi Yan Xue Ye Xue Za Zhi // Zhongguo Bing Li Sheng Li Xue Hui == Journal of Experimental Hematology // Chinese Association of Pathophysiology.  22:1142-1147. 2014
    2014 Carboxyl terminus of ADAMTS13 directly inhibits platelet aggregation and ultra large von willebrand factor string formation under flow in a free-thiol-dependent mannerArteriosclerosis, Thrombosis, and Vascular Biology.  34:397-407. 2014
    2014 DNase, ADAMTS13, and iPAD4: Good for the heartBlood.  123:10-11. 2014
    2014 Anti-ADAMTS13 IgG autoantibodies present in healthy individuals share linear epitopes with those in patients with thrombotic thrombocytopenic purpuraHaematologica.  99. 2014
    2014 Current status in diagnosis and treatment of hereditary thrombotic thrombocytopenic purpura.Hereditary Genetics.  3. 2014
    2013 Arsenic trioxide induces apoptosis in B-cell chronic lymphocytic leukemic cells through down-regulation of survivin via the p53-dependent signaling pathwayLeukemia Research.  37:1719-1725. 2013
    2013 Compromised shear-dependent cleavage of type 2N von willebrand factor variants by ADAMTS13 in the presence of factor VIIIThrombosis and Haemostasis.  110:202-204. 2013
    2013 Structure-function and regulation of ADAMTS-13 proteaseJournal of Thrombosis and Haemostasis.  11:11-23. 2013
    2013 Ticlopidine-associated ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in 22 persons in Japan: A report from the Southern Network on Adverse Reactions (SONAR)British Journal of Haematology.  161:896-898. 2013
    2013 AAV-mediated expression of an ADAMTS13 variant prevents shigatoxin-induced thrombotic thrombocytopenic purpuraBlood.  121:3825-3829. 2013
    2013 ADAMTS13, TTP and Beyond.Hereditary Genetics.  2:e104. 2013
    2013 Biochemistry and physiological functions of ADAMTS7 metalloprotease.Advances in biochemistry.  1. 2013
    2012 Antigen and substrate withdrawal in the management of autoimmune thrombotic disordersBlood.  120:4134-4142. 2012
    2012 Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: A 20-year review from the southern network on adverse reactions (SONAR)Seminars in Thrombosis and Hemostasis.  38:845-853. 2012
    2012 Light chain of factor VIII is sufficient for accelerating cleavage of von Willebrand factor by ADAMTS13 metalloproteaseJournal of Biological Chemistry.  287:32459-32466. 2012
    2012 Genetic ablation of adamts13 gene dramatically accelerates the formation of early atherosclerosis in a murine modelArteriosclerosis, Thrombosis, and Vascular Biology.  32:1817-1823. 2012
    2012 Modification of an exposed loop in the C1 domain reduces immune responses to factor VIII in hemophilia A miceBlood.  119:5294-5300. 2012
    2012 ADAMTS13 meets MR, then what?Blood.  119:3652-3654. 2012
    2012 Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpuraBlood.  119:3836-3843. 2012
    2011 Novel recombinant glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 and variants for assessment of anti-ADAMTS13 autoantibodies in patients with thrombotic thrombocytopenic purpuraThrombosis and Haemostasis.  106:947-958. 2011
    2011 Essential domains of a disintegrin and metalloprotease with thrombospondin type 1 repeats-13 metalloprotease required for modulation of arterial thrombosisArteriosclerosis, Thrombosis, and Vascular Biology.  31:2261-2269. 2011
    2011 A shear-based assay for assessing plasma ADAMTS13 activity and inhibitors in patients with thrombotic thrombocytopenic purpuraTransfusion.  51:1580-1591. 2011
    2011 Analysis of morphology of platelet aggregates formed on collagen under laminar blood flowAnnals of Biomedical Engineering.  39:922-929. 2011
    2011 Toward a definition of "fresh" whole blood: An in vitro characterization of coagulation properties in refrigerated whole blood for transfusionTransfusion.  51:43-51. 2011
    2010 Factor VIII and platelets synergistically accelerate cleavage of von Willebrand factor by ADAMTS13 under fluid shear stressJournal of Biological Chemistry.  285:28596-28603. 2010
    2010 Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpuraHaematologica.  95:1555-1562. 2010
    2010 Amino acid residues Arg659, Arg660, and Tyr 661 in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factorBlood.  115:2300-2310. 2010
    2010 ADAMTS13 testing: Why bother?Blood.  115:1475-1476. 2010
    2010 A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infectionTransfusion.  50:208-212. 2010
    2009 Leukocyte proteases cleave von Willebrand factor at or near the ADAMTS13 cleavage siteBlood.  114:1666-1674. 2009
    2009 A team player: The disintegrin domain of ADAMTS13Blood.  113:5373-5374. 2009
    2009 Von Willebrand factor cleaved from endothelial cells by ADAMTS13 remains ultralarge in sizeJournal of Thrombosis and Haemostasis.  7:1749-1752. 2009
    2009 Thromboelastography of patients after fontan compared with healthy childrenPediatric Cardiology.  30:771-776. 2009
    2009 Correction of murine ADAMTS13 deficiency by hematopoietic progenitor cell-mediated gene therapyBlood.  113:2172-2180. 2009
    2009 Enteropeptidase, a type II transmembrane serine proteaseFrontiers in bioscience (Elite edition).  1 E:242-249. 2009
    2009 Correction of ADAMTS13 deficiency by in utero gene transfer of lentiviral vector encoding ADAMTS13 genesMolecular Therapy.  17:34-41. 2009
    2009 Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin timeJournal of Thrombosis and Haemostasis.  7:80-86. 2009
    2009 Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): Review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989-2008)Kidney International.  75. 2009
    2008 Inflammatory cytokines inhibit ADAMTS13 synthesis in hepatic stellate cells and endothelial cellsJournal of Thrombosis and Haemostasis.  6:1233-1235. 2008
    2008 Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13Proceedings of the National Academy of Sciences.  105:7416-7421. 2008
    2007 Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura. A Report From the SERF-TTP Research Group and the RADAR ProjectJournal of the American College of Cardiology.  50:1138-1143. 2007
    2007 The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flowBlood.  110:1887-1894. 2007
    2006 Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine kidney cells depends on the CUB domains and their association with lipid raftsBlood.  108:2207-2215. 2006
    2006 Inhibitory autoantibodies against ADAMTS-13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS-13 protease and may accelerate its clearance in vivoJournal of Thrombosis and Haemostasis.  4:1707-1717. 2006
    2006 An evaluation of cyclosporine alone for the treatment of early recurrences of thombotic thrombocytopenic purpuraJournal of Thrombosis and Haemostasis.  4:1162-1164. 2006
    2006 Increased ADAMTS-13 proteolytic activity in rat hepatic stellate cells upon activation in vitro and in vivo.Journal of Thrombosis and Haemostasis.  4:1063-1070. 2006
    2005 Molecular biology of ADAMTS13 and diagnostic utility of ADAMTS13 proteolytic activity and inhibitor assaysSeminars in Thrombosis and Hemostasis.  31:659-672. 2005
    2005 The proximal carboxyl-terminal domains of ADAMTS13 determine substrate specificity and are all required for cleavage of von Willebrand factorJournal of Biological Chemistry.  280:29428-29434. 2005
    2004 Binding of platelet glycoprotein Ibα to von Willebrand factor domain A1 stimulates the cleavage of the adjacent domain A2 by ADAMTS13Proceedings of the National Academy of Sciences.  101:10578-10583. 2004
    2004 Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpuraBlood.  103:4043-4049. 2004
    2003 Cleavage of the ADAMTS13 Propeptide Is Not Required for Protease ActivityJournal of Biological Chemistry.  278:46643-46648. 2003
    2003 Structure and Function of ADATMS13, a metalloprotease that regulates thrombosisJapanese Journal of Thrombosis and Hemostasis.  14. 2003
    2003 Cleavage of von Willebrand factor requires the spacer domain of the metalloprotease ADAMTS13Journal of Biological Chemistry.  278:30136-30141. 2003
    2003 Remission of chronic thrombotic thrombocytopenic purpura after treatment with cyclophosphamide and rituximabAnnals of Internal Medicine.  138:105-108. 2003
    2002 Mucin-like domain of enteropeptidase directs apical targeting in Madin-Darby canine kidney cellsJournal of Biological Chemistry.  277:6858-6863. 2002
    2002 ADAMTS13 and TTPCurrent Opinion in Hematology.  9:389-394. 2002
    2001 Structure of von Willebrand Factor-cleaving Protease (ADAMTS13), a Metalloprotease Involved in Thrombotic Thrombocytopenic PurpuraJournal of Biological Chemistry.  276:41059-41063. 2001
    1999 Crystal structure of enteropeptidase light chain complexed with an analog of the trypsinogen activation peptideJournal of Molecular Biology.  292:361-373. 1999
    1999 Differential activity of diethylstilbestrol versus estradiol as neonatal endocrine disruptors in the female hamster (Mesocricetus auratus) reproductive tractBiology of Reproduction.  61:91-100. 1999
    1999 Apical sorting of bovine enteropeptidase does not involve detergent- resistant association with sphingolipid-cholesterol raftsJournal of Biological Chemistry.  274:1596-1605. 1999
    1998 Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in miceProceedings of the National Academy of Sciences.  95:7603-7607. 1998
    1998 Activation of thrombin-activable fibrinolysis inhibitor requires epidermal growth factor-like domain 3 of thrombomodulin and is inhibited competitively by protein CJournal of Biological Chemistry.  273:12135-12139. 1998
    1998 Structure of murine enterokinase (enteropeptidase) and expression in small intestine during developmentAJP - Gastrointestinal and Liver Physiology.  274. 1998
    1998 Structure of murine enterokinase (enteropeptidase) and expression in small intestine during development.American Journal of Physiology.  274:G342-G349. 1998
    1997 Bovine proenteropeptidase is activated by trypsin, and the specificity of enteropeptidase depends on the heavy chainJournal of Biological Chemistry.  272:31293-31300. 1997
    1997 Endometrial hyperplasia and apoptosis following neonatal diethylstilbestrol exposure and subsequent estrogen stimulation in both host and transplanted hamster uteriCancer Research.  57:1903-1908. 1997
    1997 Neonatal diethylstilbestrol treatment alters the estrogen-regulated expression of both cell proliferation and apoptosis-related proto-oncogenes (c-jun, c-fos, c-myc, bax, bcl-2, and bcl-x) in the hamster uterusCell Growth and Differentiation.  8:425-434. 1997
    1996 Effect of protein C inhibitor (PCI) on in vitro fertilizationImmunopharmacology -New York-.  33:140-142. 1996
    1996 Protein C inhibitor (PCI)Immunopharmacology -New York-.  32:53-56. 1996
    1994 Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa.American Journal of Physiology.  267:C466-C472. 1994
    1994 Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoaAmerican Journal of Physiology - Cell Physiology.  267. 1994
    1994 Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoaAmerican Journal of Physiology - Cell Physiology.  267. 1994
    1994 Serine protease inhibitors (serpins) in human seminal plasma: Concentrations and inhibition of acrosinFibrinolysis.  8:364-371. 1994
    ADAMTS13 and its variants promote angiogenesis via upregulation of VEGF and VEGFR2.Cellular and molecular life sciences : CMLS
    ADAMTS13 and von Willebrand factor interactions.Current Opinion in Hematology
    ADAMTS13 autoantibodies cloned from patients with acquired thrombotic thrombocytopenic purpura: 1. Structural and functional characterization in vitro.Transfusion
    ADAMTS13 autoantibodies cloned from patients with acquired thrombotic thrombocytopenic purpura: 2. Pathogenicity in an animal model.Transfusion
    Acquired autoimmune thrombotic thrombocytopenic purpura in a case of severe haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia
    High-resolution epitope mapping by HX MS reveals the pathogenic mechanism and a possible therapy for autoimmune TTP syndrome.Proceedings of the National Academy of Sciences of the United States of America
    Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura.Haematologica

    Book

    Year Title Altmetric
    2008 Pathogenesis of thrombotic microangiopathies.  Ed. 3.  2008

    Chapter

    Year Title Altmetric
    2017 Data interpretation in laboratory medicine.  489-510. 2017
    2015 Adamts13: Structure and function.  39-57. 2015

    Research Overview

  • My lab has been interested in studying the mechanism of normal and abnormal blood coagulation, specifically the pathogenesis of immune thrombotic thrombocytopenic purpura (TTP). TTP is a potential fatal blood disorder, resulting from the deficiency of a plasma ADAMTS13 protease, which is essential for the cleavage of von Willebrand factor (VWF), thereby regulating normal hemostasis. Deficiency of this protease results in uncontrolled platelet adhesion and aggregation and thrombus formation throughout the body. Patients with such a condition is universally fatal unless being diagnosed and treated immediately with plasma exchange.

    My lab has been working on 1) biology of ADAMTS13 protease; 2) regulation of ADAMTS13 function, and 3) the molecular mechanisms of TTP. We employed various cutting-edge tools including biochemistry, molecular biology, biophysics, and animal models to help understand the pathogenesis of TTP and establish novel therapeutics for TTP.
  • Teaching Overview

  • I am passionate about medical and science eduction. In the past decade, I have trained more than two dozens of postdoctoral fellows, clinical fellows, residents, graduate students, and undergraduate students. Most of them have gone on to establish their own academic career (teaching, patient care, and research) around the globe. I am very proud of their accomplishments.
  • Education And Training

  • Tongji Hospital, Huazhong University of Science and Technology Obstetrics and Gynecology, Residency
  • Doctor of Philosophy in Molecular Biology, Medical University of Vienna 1994
  • Doctor of Medicine, Nanchang University 1984
  • Washington University in St. Louis Department of Pathology and Lab Medicine, Residency 2002
  • Washington University St. Louis Department of Medicine and Howard Hughes Medicine Institute, Residency 1999
  • Washington University St. Louis Department of Pathology and Lab Medicine, Postdoctoral Fellowship 2003
  • Full Name

  • X. Long Zheng