Dana Abendschein, PhD

Associate Professor of Medicine

Safe, Effective Treatment of Thrombosis and Vascular Injury Read More

Email: dabendsc@wustl.edu
Lab Phone: (314) 362-8930
Website: Abendschein Lab
Lab Location: 9922 Clinical Sciences Research Building
Keywords: vascular biology, blood coagulation, diabetes, inflammation

Safe, Effective Treatment of Thrombosis and Vascular Injury

Research in this translational physiology laboratory focuses primarily on development of safe and effective antithrombotic approaches for use during acute myocardial infarction and stroke. Currently, we are working with recombinant versions or fragments of physiologic anticoagulants and antiplatelet compounds to increase targetability and minimize side effects. One such compound was derived from human nucleoside triphosphate diphosphohydrolase-3 (CD39L) or apyrase found on endothelium that degrades ATP to ADP, and ADP to AMP.  This is important because ATP is pro-inflammatory and ADP is prothrombotic; activating platelets that comprise the thrombus.  An optimized recombinant form of the protein, APT102, was shown to prevent thrombotic reocclusion and decrease reperfusion injury/infarction after coronary occlusion and reperfusion in dogs and mice without increasing bleeding or hemorrhage.   This may be a huge benefit that we plan to study next during treatment of ischemic stroke because bleeding risk prevents any antithrombotic agents from being given during fibrinolysis with rt-PA.  Other recent studies have focused on development of fusion proteins comprised of antiplatelet or anticoagulants proteins fused to annexin V that targets the fusion protein to phosphotidylserine exposed on activated or injured cells.  The targeting effect would serve to concentrate the inhibitor to the area of active thrombosis or vessel injury.  We are also interested in applying nanoparticulate delivery systems that could be used together with or independent of a supporting vascular stent to provide targeted and safe antithrombotic therapy after vascular injury. In order for many of the cardiovascular therapeutics to have application in ischemic stroke and cerebral vascular diseases, large animal models that mimic the pathophysiology of human ischemic stroke are needed. Collaboration with Hope Center investigators will provide exciting opportunities to bring new treatments to bear on ischemic stroke, subarachnoid hemorrhage, and other types of cerebral vascular injuries. Trainees in the lab would be responsible for conducting hands-on experiments in intact animal models of disease and vascular injury; developing strategies using MRI, PET, or optical imaging to image vessels, thrombosis, and associated inhibitors; using assays for coagulation protease activities, histopathologic analysis of therapeutic efficacy; computing the statistical significance of data; and composing results of studies for presentation and publication.

Updated Augutst 2014