Reheman (Raymond) Adili, M.D.

Area of Study in detail:

• Platelet physiology and thrombosis

Thrombotic diseases such as heart attack, stroke, and venous thromboembolism are the leading causes of mortality and morbidity worldwide. Platelets, the smallest blood cells, play central roles in these diseases. We have a long-term interest in elucidating how platelets interact with various proteins in plasma and vessel walls to form thrombosis under disease conditions. Using multiple advanced techniques, including multi-channel high-speed intravital confocal microscopy, platelet aggregometer, and microfluidic devices, we have deepened our understanding of this pathophysiological process at cellular and molecular levels.

• Pathophysiology of microvascular thrombosis

Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening disease characterized by systemic microvascular thrombosis. It is associated with ADAMTS13 deficiency, a von Willebrand factor (VWF) cleaving protease in plasma. However, the pathophysiology of microvascular thrombosis in TTP is not well understood. Taking advantage of real-time intravital microscopic imaging in mice, we can monitor VWF-mediated-platelet thrombi formation in microvessels and examine the effect of potential therapeutic agents on preventing or breaking down the thrombi. In collaboration with Dr. Lopez’s lab, we have shown that N-acetylcysteine (NAC) effectively prevents microvascular thrombosis in vivo in TTP (J Clin Invest.2011, 121:593). Recently our lab has shown that VWF self-association, a process of dynamic assembly of VWF strands and fibers, initiates platelet adhesion and thrombus formation in microcirculation in mice. Surprisingly, these processes do not require platelet activation and fibrin formation. Treatment of recombinant ADAMTS13 prevents VWF self-association and dissolves brain microvascular thrombosis in mice (ATVB 2019, 39:1817).  We will continue studying the underlying pathogenesis and pathophysiology of TTP and testing new agents that break down microvascular thrombosis.

• Restoring hemostasis in bleeding disorders

Bleeding disorders and abnormal hemostasis are caused by dysfunctions of platelet, coagulation factor, or endothelium, and can be inherited, such as hemophilia, or acquired due to antithrombotic therapy. Currently, there are limited therapeutic agents available to restore hemostasis and prevent bleeding caused by antithrombotic treatments. Our lab is studying the effect of snake venom-derived hemocoagulase on hemostatic clot formation and bleeding in hypocoagulant conditions in vivo using intravital microscopy and bleeding assays, and ex vivo using thromboelastography and platelet function tests. The preliminary data show that a snake venom-derived hemocoagulase may be a novel hemostatic agent to limit bleeding in hemophilia and reverse the effect of antithrombotic treatments.

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