2020 IARS Mentored Research Award

Yusuke Sugasawa, MD, PhD
Juntendo University School of Medicine
Clinical Associate Professor
Tokyo, Japan

Dr. Sugasawa’s Research

Structural basis of lipid and anesthetic action on TMEM16 scramblases

The TMEM16 family of membrane proteins are Ca2+-dependent phospholipid scramblases. A critical function of TMEM16 scramblases is the externalization of phosphatidylserine (PS), which predominately resides in the inner leaflet of the plasma membrane. Exposure of PS is essential for platelet-mediated activation of blood coagulation as well as regulation of apoptosis and inflammatory responses. We show that the TMEM16 scramblase, nhTMEM16, is inhibited by cholesterol in a liposome scramblase assay. Also, recent studies have shown that TMEM16 scramblases are modulated by various lipids such as long-chain phospholipids and ceramides. Thus, lipid modulators offer a potential avenue to modulate TMEM16 scramblase activity and physiologic processes such as coagulation and neuroapoptosis, which are particularly relevant in the perioperative period. The molecular mechanisms by which TMEM16 scramblases are modulated by lipids are not understood, and whether other hydrophobic molecules such as anesthetics modulate TMEM16 scramblases is unknown. The overarching goal of this project is to characterize the pharmacology of lipid and anesthetic modulation of nhTMEM16, and determine the stoichiometry and sites of binding that mediate the modulatory effects. Since anesthetics also affect blood coagulation, apoptosis and inflammatory responses resulting in adverse clinical outcomes, we will test the hypothesis that TMEM16 scramblases are modulated by anesthetics. The outcome of this project will provide novel information on the sites of small molecule modulation of TMEM16 scramblases, which may facilitate structure-based design of TMEM16 modulators.

Encourage, stimulate, and fund ongoing anesthesia-related research projects that will enhance and advance the specialty, and to disseminate current, state-of-the-art, basic and clinical research data in all areas of clinical anesthesia, including perioperative medicine, critical care, and pain management. The IARS is focused solely on the advancement and support of education and scientific research related to anesthesiology.

A&A Case Reports

IMRA Awards

This award is intended to support investigations that will further the understanding of clinical practice in anesthesiology and related sciences. Up to four research projects are selected annually, with a maximum award of $175,000 each, payable over two years.

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