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  UPCOMING EVENTS   Selected Seminar        
     
 
Date: 9 March 2017
Time: 11:00am | Level 3, IMCB Seminar Room 3-46, Proteos
Speaker: Prof. Junichi Sadoshima
Title: Molecular mechanisms of heart failure: a central role of the Hippo pathway

The Hippo pathway controls organ size through regulation of apoptosis and proliferation. Serine threonine kinases, including mammalian sterile 20-like 1 (Mst1) and large tumor suppressor 1/2 (Lats1/2), and transcription co-factors, including Yes-associated protein (YAP) and Taz, are the key components of the Hippo pathway. Mst1 and Lats2 are activated by stress, which in turn phosphorylates YAP and suppresses its function, and mediate the progression of heart failure. YAP promotes survival and cardiac hypertrophy/proliferation through regulation of TEAD and FoxO, and miRNAs, including miR-206. Stress-induced activation of the Hippo pathway inhibits YAP, thereby inducing apoptosis, suppressing compensatory hypertrophy, and facilitating cardiac dysfunction. Excessive downregulation of the Hippo pathway and/or persistent activation of YAP, however, induce dedifferentiation of cardiomyocytes (CMs) and contractile dysfunction through stimulation of TEAD. Thus, CMs under stress risk their own death by apoptosis by activating the Hippo pathway in order to maintain the differentiation status and contraction against hemodynamic overload. It would be important to keep the activity of the Hippo pathway within an appropriate range, in order to suppress cell death and, at the same time, to maintain the differentiation status of CMs. I will discuss physiological and pathological roles of the Hippo pathway during heart failure.

Biography:
Dr. Sadoshima received his MD/PhD from Kyushu University School of Medicine, in Fukuoka, Japan. He is currently Professor and Chair of the Department of Cell Biology and Molecular Medicine at Rutgers. His research has been supported by multiple NIH R01 grants since 2000. He has published over 260 papers focusing on the signaling mechanisms of heart failure. He discovered that oxidation of cysteine residues induces nuclear exit of class II histone deacetylases, thereby inducing cardiac hypertrophy (Cell 2008). He also demonstrated that Mst1 phosphorylates Beclin 1, thereby suppressing autophagy in the heart (Nat Med 2013). He received the AHA’s Katz Basic Science Research Prize (1995) and the Thomas Smith Memorial Lecture Award (2014). He serves on editorial teams in JCI, Circ Res and Autophagy. He will organize a Keystone symposium entitled, “Mitochondria, metabolism and heart”, in May 2017. He has been a member of the American Society of Clinical Investigation since 2002. He has been serving on NIH study sections and NMRC review committees. He has been the North American coordinator of the Fondation Leducq’s Transatlantic Network focusing on autophagy since 2016. His trainees have received numerous awards, including Katz awards and Marcus awards from the AHA.


Host: Dr. Marius Sudol


 
     

 
 
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