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Research Summary

Our laboratory focuses on the molecular mechanism of thrombosis and hemostasis. In particular, my colleague and I are trying to understand the pathogenesis of immune thrombotic thrombocytopenic purpura (iTTP), a rare but potentially fatal blood disorder.

Pathogenesis of TTP

ITTP is primarily caused by severe deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF), resulting from acquired autoantibodies against ADAMTS13. The antibodies bind and inhibit plasma ADAMTS13 activity, which hinders the cleavage of VWF, resulting in heightened platelet adhesion and aggregation (Fig. 1).

Despite progresses being made in past decades, major gaps remain. Our lab is actively investigating on: 1) How neutrophils, neutrophil activation, and NETosis may play a role in the onset, progression, and outcomes of iTTP; 2) How distinct molecular signatures in the complementarity determining region (CDR) 2/3 in the variable region of autoantibodies against ADAMTS13 may determine their functions (e.g., inhibitory and activating); and 3) How abnormalities in complement regulatory factors such as complement factor H (CFH) and ANKRD26/36 gene family may play a role in pathogenesis of iTTP.

The results of our study may provide novel insight into the pathogenesis of iTTP, which helps development of novel therapeutic strategy for iTTP. Our findings may change how we manage patients with acute iTTP today.

The laboratory employs cutting-edge research tools, including molecular cloning, PCR, CRISPR/cas9, protein engineering and purification, Isothermal titration calorimetry (ITC), fluorescent spectroscopy, single molecular laser tweezer, microfluidic shear-based and intra vital thrombus formation assays, as well as various animal models including mice and zebrafish for the projects.  

KU School of Medicine

University of Kansas Medical Center
Department of Pathology & Laboratory Medicine
Mail Stop 3045
3901 Rainbow Boulevard
Kansas City, KS 66160
Phone: 913-588-7070
Fax: 913-588-7073