X. Long
M.D, Ph.D
Abramson Research Center 816G The Children's Hospital of Philadelphia The 34th Street & Civic Center Blvd,
(215) 590-3565

Director of Hematology and Coagulation Laboratories.

Areas of Interest:

Hemostasis and thrombosis,
Transfusion medicine,
Thrombotic thrombocytopenic purpura (TTP),
Hemolytic uremic syndrome (HUS),
Hemophilia and thrombophilia,
Platelet dysfunctions, and
Thrombotic/bleeding complications during pregnancy.

Hereditary Genetics-Current Research
Associate Editor,
Journal of Thrombosis and Haemostasis
Section Editor,
Archives of Pathology and Laboratory Medicine
Editorial board member,
Advances in Biochemistry
World J Stem Cell
Pathology and Laboratory Medicine International
Journal of Biotechnology & Biomaterials

1) Structure-function analysis of ADAMTS13 and ADAMTS7;
2) Cofactor-dependent regulation of ADAMTS13 and ADAMTS7 function;
3) Hydrogen-deuterium exchange and mass spectrometry determine epitopes of anti-ADAMTS13 autoantibodies;
4) Autophagy in regulation of von Willebrand factor (VWF) secretion and function; and
5) Inflammation, neutrophil activation, and proteolysis of VWF by ADAMTS13.


ADAMTS13, a plasma metalloprotease, cleaves von Willebrand factor (vWF) and regulates vWF multimer sizes. Deficiency of ADAMTS13 activity leads to thrombotic thrombocytopenic purpura (TTP) and many other arterial thrombotic disorders. My colleague and I are interested in understanding of the pathogenesis of TTP by investigating the structural components of ADAMTS13 protease required for substrate recognition in vitro and in vivo. We are also interested in determining the epitopes anti-ADAMTS13 IgG autoantibodies bind. Finally, we are interested in identifying novel protein or non-protein cofactors that accelerate ADAMTS13 enzymatic function and in developing viral vector and cell-based molecular therapies for treatment of TTP and related disorders.

ADAMTS7, a closely related metalloprotease to ADAMTS13, cleaves cartilage oligomeric matrix protein (COMP). It has recently been identified as a risk factor for atherosclerosis and cardiovascular diseases. Little is known about the biochemistry and physiological functions of ADAMTS7 in atherosclerosis and thrombosis. My colleague and I are interested in understanding of the structure-function relationship of ADAMTS7 in recognition of novel substrates. In addition, we are interested in developing novel fluorescein-labeled peptide assays for assessing plasma ADAMTS7 activity in patients with various cardiovascular diseases.

Recombinant DNA and protein engineering, protein expression and purification, cell culture, light/fluorescent microscopy, confocal and electron microscopy, various other biochemical and biophysical assays, and murine models will all be employed in the laboratory.

The advances in these areas will not only shed more light on the pathogenesis of TTP and atherosclerosis, but also provide tools for diagnosis and treatment of TTP and many other arterial thrombotic disorders including myocardial infarction and ischemic stroke.


S. Liang, M.D., Lab manager,
B. Pickens, PhD, Postdoctoral fellow,
J. Bao, PhD, Postdoctoral fellow,
Y. Mao, PhD, Postdoctoral fellow,
V. Pillai, PhD, Postdoctoral fellow,
H. Hanby, PhD Graduate student,
R. Lu, MD, PhD, Visiting scholar,
J. Mao, PhD, Visiting scholar.


1. Structural function study of ADAMTS13 and ADAMTS7
2. Cofactor-dependent regulation of ADAMTS13 and ADAMTS7 function
3. Development of novel diagnostic tools for thrombotic thrombocytopenic purpura and hemolytic uremic syndrome
4. Identification of antibody binding epitope using deuterium hydrogen exchange plus mass spectrometry
5. Using murine models of thrombotic thrombocytopenic purpura to test novel therapeutic efficacy
6. Understanding of the role of ADAMTS13 and ADAMTS7 proteases in the development of atherosclerosis and inflammation.

Assistant Professor of Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (2003 – 2011)
Associate Professor of Pathology and Laboratory Medicine at University of Pennsylvania School of Medicine (2011 – 2015)
Fellowship, Transfusion Medicine, Washington University School of Medicine, St. Louis, MO (2003)
Residency, Clinical Pathology, Washington University School of Medicine, St. Louis, MO (2002)
Ph.D., Molecular and Cell Biology, Medical University of Vienna, Vienna, Austria (1994)
M.D., Medicine, Nanchang University Medical College, Nanchang, China (1984)
Selected Publications
Bao J., Xiao J., Mao J., and Zheng X.L.. Carboxyl-terminus of ADAMTS13 directly inhibits platelet aggregation and ultra large VWF string formation under flow in a free thiol-dependent manner.. Arterosclerosis, Thrombosis, and Vascular Biology (ATVB). Vol In press. 2013 December.
Jin S.Y., Xiao J., Bao J., Zhou S.Z., Wright J.F., and Zheng X.L.. AAV-mediated expression of an ADAMTS13 variant prevents shigatoxin-induced thrombotic thrombocytopenic purpura. Blood. Vol 121(19) . 2013 May:3825-3829.
Zheng X.L.. Structure-function and cofactor-dependent regulation of ADAMTS13 protease. J. Thromb. Haemost.. Vol 11(Suppl. 1) . 2013 June:11-23.
Cao W.J., Sabatino D.E, Altynova E., Lange A.M., Casina V.C., Camire R.M. and Zheng X.L.. Light Chain of Factor VIII Is Sufficient for Accelerating Cleavage of von Willebrand Factor by ADAMTS13 Metalloprotease. J. Biol. Chem.. Vol 287(39) . 2012 August:32459?32466..
Jian C., Xiao J., Gong L., Skipwith C.G., Jin S-Y, Kwaan H-C, and Zheng X.L.. Gain-of-function ADAMTS13 variants that are resistant to inhibition by autoantibodies in patients with acquired idiopathic thrombotic thrombocytopenic purpura.. Blood. Vol 119(16) . 2012 April:3836-43..
Jin S-Y., Tohyama J., Bauer R.C., Cao N.N, Rader D.J., and Zheng X.L.. Genetic ablation of Adamts13 gene dramatically accelerates the early atherosclerosis in a murine model.. Arteriscler. Thromb. Vasc. Biol. (ATVB). Vol 32. 2012 August:1817-1823.
Zheng X.L.. ADAMTS13 Meets MR, then What?. Blood. Vol 119(16) . 2012 April:2652-54..
Xiao J., Jin S-Y., Xue J., Sorvillo N., Voorberg J., and Zheng X.L.. Essential Domains of ADAMTS13 Metalloprotease Required for Modulation of Arterial Thrombosis. Arterioscler. Thromb. Vasc. Biol. (ATVB).. Vol 31. 2011 October:2261-2269.
Skipwith C., Cao W., and Zheng X.L.. Factor VIII and platelets synergistically accelerate cleavage of von Willebrand factor by ADAMTS13 under fluid shear stress. J. Biol. Chem.. Vol 285(37) . 2010 September:28596-603..
Jin S.Y., Skipwith C.G., and Zheng X.L.. Amino acid residues Arg659, Arg660 and Tyr661 in the spacer domain of ADAMTS13 are critical for cleavage of von Willebrand factor. Blood. Vol 115(11) . 2010 March:2300-10..