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HRI & CI Medical Research Seminar: Thrombotic Disease

02/07/2019 @ 12:00 pm - 1:00 pm

Medical Research Seminar: Protein Disulfide Isomerase Inhibition in Thrombotic Disease

Dr Robert Flaumenhaft
Professor of Medicine, Harvard Medical School; Chief, Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center

Abstract

Protein disulfide isomerase (PDI) is an essential component of in vivo clot formation. Using a high throughput screen, we identified rutin and isoquercetin as inhibitors of PDI. These compounds also inhibited in vivo thrombus formation. Following oral ingestion in humans, isoquercetin inhibited platelet-dependent thrombin generation in a PDI-dependent manner. Isoquercetin was subsequently evaluated in a phase II study of patients with advanced cancer to assess its effect on hypercoaguability. Isoquercetin ingestion resulted in PDI inhibitory activity in plasma, reduced D-dimer levels, reduced soluble P-selectin levels, and inhibited platelet-dependent thrombin generation ex vivo. While ~20% of patients experienced a thrombotic event in a similarly designed study, none of the patients receiving isoquercetin demonstrated DVT or PE during this study. Five incidental catheter-associated DVT or superficial clots that did not meet the prespecified VTE endpoint criteria were detected. There were no severe adverse events attributable to isoquercetin. No major hemorrhages were observed.

Bio

Robert Flaumenhaft, M.D., Ph.D. is Professor of Medicine at Harvard Medical School and Chief of the Division of Hemostasis and Thrombosis at Beth Israel Deaconess Medical Center, where he supervises a lab focused on platelet granule secretion and thrombosis. His work has been recognized by awards from HHMI, the Burroughs Wellcome fund, AHA, and ASH, as well as by election to the American Society of Clinical Investigators. He is currently supported by an Outstanding Investigator Award from NIH. Dr. Flaumenhaft is Director of the T32 Program in Blood Coagulation and Vascular Biology. He serves on the editorial boards of many journals within the field and is a standing member of the Hemostasis and Thrombosis study section. His scientific accomplishments include elucidating of the role of SNARE proteins in platelet granule secretion, demonstrating molecular underpinnings of the prothrombotic transformation of endothelium during inflammation, and showing that protein disulfide isomerase is a viable target for antithrombotic therapy.

Learn more about Dr Robert Flaumenhaft’s Research here.

Download the poster here.

Details

Date:
02/07/2019
Time:
12:00 pm - 1:00 pm
Event Category:

Venue

Centenary Institute Lecture Theatre, Building 93, Royal Prince Alfred Hospital Camperdown, New South Wales 2050 Australia