Yasuchika Takeishi, MD, PhD, FAHA, FESC, FISHR

Keywords: Cardiology, Heart failure, Signal transduction, Innate immunity

Yasuchika Takeishi is Professor and Chairman, Department of Cardiovascular Medicine at
Fukushima Medical University and is responsible for advancing patient care, research, andeducation at Fukushima Medical University. A 1987 graduate of Yamagata University School ofMedicine, he later earned positions at the University of Cincinnati and Case Western Reserve
University (1997-2000), and was trained through the NIH-sponsored Specialized Centers ofResearch in Heart Failure program, which pioneered the use of genetically engineered mice toelucidate mechanisms of cardiac hypertrophy and heart failure. Since 2008, Dr. Takeishi has been
Professor and Chair of the Department of Cardiovascular Medicine at Fukushima MedicalUniversity.
The global burden of heart failure has motivated Takeishi to focus on how aberrant signaltransduction pathways can alter cardiac size and function. Seeing the important role of protein
kinase C in the development of cardiac hypertrophy and its progression to heart failure, he foundin vitro evidence that controlling cellular levels of diacylglycerol (DAG) and its downstream
signalling cascade by DAG kinase was responsible for cardiomyocyte hypertrophy. Using
genetically engineered mice, DAG kinase blocked cardiac remodelling after pressure overload
and myocardial infarction in vivo. DAG kinase also prevented progressive heart failure and lethal
arrhythmias in mice overexpressing constitutively active Gq.
Pioneers in cellular and humoral innate immunity inspired Takeishi to investigate the rolesof Toll-like receptor (TLR) and pentraxin 3 in heart failure. He found that TLR-2 modulated
ventricular remodelling after myocardial infarction and doxorubicin-induced cardio-toxicity
through production of inflammatory cytokines. Pentraxin 3 produced from bone marrow-derived
cells, rather than cardiac resident cells, played a crucial role in cardiac protection against
myocardial ischemia/reperfusion injury by attenuating infiltration of neutrophils, generation ofreactive oxygen species and inflammatory cytokines.

The changing landscape of healthcare delivery has motivated Takeishi to investigate
clinical biomarkers to stratify the risk of heart failure patients; some novel candidate markershave emerged from this research. Additionally, he has performed molecular imaging withpositron emission tomography to characterize metabolic and inflammatory status of the failingheart. Recently, he has investigated the role of clonal hematopoiesis, a novel link between aging
and cardiovascular diseases. He found that clonal hematopoiesis with JAK2V617F causally leadto development of pulmonary hypertension and aortic aneurysm.
Productive collaboration with mentors, colleagues, and trainees has yielded more than 500
papers in Nature Communications, Journal of Clinical Investigation, Circulation, Circulation
Research, Journal of the American College of Cardiology, Cardiovascular Research, Journal of
Molecular and Cellular Cardiology, and others. Takeishi has served as the editor-in-chief ofJournal of Cardiology and associate editor of Circulation Journal (Japanese Circulation Society)and worked as an editorial board member of various others.