Bioactive Lipids in Cancer, Inflammation and Related Diseases

Takao Shimizu, M.D., Ph.D.

Takao Shimizu, M.D., Ph.D.

Takao Shimizu, M.D., Ph.D., is a professor at the University of Tokyo and serves as a Project Leader of National Center for Global Health and Medicine. He was recently appointed as the director of the Institute of Microbial Chemistry, Tokyo, Japan.  He is globally recognized for his scientific achievement in the field of lipid metabolism in health and diseases. He was the first to isolate arachidonate 5-lipoxygenase and found that the enzyme also catalyzes dehydration to yield leukotriene A4 by its 8-lipoxygenase activity.


Takao Shimizu graduated from medical school of the University of Tokyo in 1973. After a 2-year clinical training at the University Hospital, he joined Professor Osamu Hayaishi’s group at Kyoto University, where he worked on the isolation of indoleamine 2,3-dioxygenase, prostaglandin D synthase and 15-PG dehydrogenase and received his Ph.D. in 1980. He conducted his postdoctoral training at the Karolinska Institute in Stockholm, Sweden, under the guidance of Professor Bengt Samuelsson, who received the Nobel Prize in Physiology or Medicine in 1982 for his discoveries concerning prostaglandins, together with Drs. Sune Bergström and John Vane. While working with Dr. Samuelsson at the Karolinska, Dr. Shimizu devoted his work on the isolation and purification of 5-lipoxygenase and elucidated the mechanism of leukotriene A4 biosynthesis by the enzyme 5-LOX, the central intermediate of leukotriene production.


Upon returning to the University of Tokyo, Dr. Shimizu focused on the isolation of the leukotriene A4 hydrolase enzyme, which is important to the biosynthesis of leukotriene B4, and then on the identification of the G protein-coupled receptors key in evoking leukotriene B4’s actions.  With collaborators, he worked on the enzymology of 5-lipoxygease, leukotriene A4 hydrolase, organic synthesis and identification of lipid mediators by GC-MS.  He identified via expression cloning the PAF receptors, leukotriene B4 receptors (BLT1 and BLT2) and later LPA receptors (LPA4 and LPA6), while establishing and analyzing mice which lack enzymes and receptor of bioactive mediators.  Among them, he analyzed very extensively the phenotypes of cytosolic phospholipase A2a (cPLA2a) in both physiology (reproduction and brain) and pathology (inflammation, immune disorders, ischemia-reperfusion injury etc.).


Professor Shimizu and his laboratory members worked on enzymes and receptors of bioactive lipid mediators (cytosolic phospholipase A2, receptors for platelet-activating factor, leukotriene B4 etc.) He analyzed the roles of these molecules by phenotype analyses of either knockout mouse and human samples. In the last decade, he moved his interests to how arachidonic acid is positioned at sn-2 of glycerophospholipids and identified more than 10 lysophospholipid acyltransferase genes. By combining both knockout mouse analyses and quantitative lipidomics with LC-MS, he is currently studying the roles of membrane fatty acid diversity in health and diseases.


His current research focus is on lysophospholipid acyltransferases, which is a molecular basis of membrane diversity and fatty acid asymmetry.  By enzyme knockout, he found that arachidonic acid is not only important for eicosanoid biosynthesis, but important for triglyceride transport and lipoprotein production.  He also uncovered that docosahexaenoic acid (DHA) plays pivotal roles in retinal development and sperm maturation.


Dr. Shimizu is an exceptional mentor and innovator who has trained many leading scientists in the field today.  At the University of Tokyo, he trained around 100 graduate students, more than 20 of whom now serve as professors at universities or oversee laboratories in Europe and North America. Dr. Shimizu has served as Dean of the School of Medicine and Vice President of the University of Tokyo.


Professor Shimizu is an invited honorary member of the Association of American Physicians.  He is the recipient of the Ernst Schering Prize in 2000, Germany, the 50th Memorial Lecture Award of Journal of Lipid Research in 2009, USA, and in 2013, he received both the Lifetime Achievement Award at the Phospholipase A2 Meeting, and the Outstanding Achievement Award from Eicosanoid Research Foundation, USA. In Japan, he received a number of prestigious awards including, but not limited to, the Medical Award from the Japanese Medical Association (2000), Medical Award of Takeda Science Foundation (2003), Japan Academy Prize (2009) and the Order of the Sacred Treasure (Gold Rays with Neck Ribbon) from the Emperor (2020). He served as Editorial Board of the Journal of Biological Chemistry, for 18 years, and the Journal of Lipid Research for 8 years.


Dr. Shimizu has been an innovative leader in the field of eicosanoids, lipid mediators and phospholipid metabolism for over 40 years.  With over 450 publications, with h-index of 106, and numerous seminal discoveries he continues to collaborate with clinical researchers and pharmaceutical companies for the analyses of human diseases and development of new lipid related drugs.