Principal Investigator, MBI
Associate Professor, Department of Biological Sciences and Department of Biomedical Engineering, National University of Singapore
Mechanotransduction, Mechanosensing; Cancer Biology (Mechano-oncology); Neurobiology (Mechano-neurology); Signal transduction through mechanical modulation of signaling proteins. Implications of mechanical factors in cell functions and biological phenomena including development, tissue regeneration, cardiovascular disorder, angiogenesis, neurogenesis, carcinogenesis and biological events.
Mechanical factors are critical in defining both shape and function of the cells and organs of all living things from prokaryotes to eukaryotes. Diverse biological phenomena such as development, tissue regeneration, cardiac hypertrophy, atherosclerosis, neurogenesis, neuronal differentiation, as well as carcinogenesis are related to or modified by mechanical environments.
To explore signal transduction induced by external stimuli, identification of specific receptors is crucial. However, specific force receptors, i.e. mechano sensors that are directly modulated by mechanical stimuli and initiate intracellular signaling cascades, were not identified at a molecular level, with the exception of mechano-sensitive ion channels. We postulated that direct mechano-sensors should be deformed by physical force and might not be totally diffusive in the cytoplasm. Thus, our recent work has sought to identify an ion channel-independent mechanosensor in the cytoskeleton.
Dr Sawada received his MD from the University of Tokyo, Japan. After six years’ clinical training as an orthopaedic surgeon, he joined the graduate programme and received his Ph.D. from the University of Tokyo. While he then returned to the clinical practice at the University of Tokyo Hospital, he resumed basic research in 2000 as a Post-doctoral fellow at Prof Michael Sheetz lab, Columbia University in the city of New York. Since then, he has been consistently working on the mechanism of how cells sense ‘force’ and convert physical information into biological events. He joined NUS in November 2007 as an Assoc Prof at the Department of Biological Sciences and Department of Biomedical Engineering.
His group is currently trying to expand the “Mechano-World” to diverse and broad research areas, including oncology, neurology, immunology and musculo-skeletal biology.
Yamauchi S, Kawauchi K, Sawada Y. Myosin II-dependent exclusion of CD45 from the site of Fcg receptor activation during phagocytosis. FEBS Letters. (2012) in press
Matsui H. Harada I, and Sawada Y., Src, p130Cas and mechanotransduction in cancer cells, Genes and Cancer. (2012) in press
Kawauchi K, Tan WW, Araki K, Abu Bakar FB, Kim M, Fujita H, Hirata H, and Sawada Y., p130Cas-dependent actin remodeling regulates myogenic differentiation, Biochem J. (2012) in press (DOI: 10.1042/BJ20112169)
Shimizu T, Ueda J, Ho JC, Iwasaki K, Poellinger L, Harada I, and Sawada Y. Dual Inhibition of Src and GSK3 Maintains Mouse Embryonic Stem Cells, Whose Differentiation Is Mechanically Regulated by Src Signaling, Stem Cells, (2012) in press (DOI: 10.1002/stem.1119 [Epub ahead of print])
Sawada, Y., M. Tamada, B.J. Dubin-Thaler, O. Cherniavskaya, R. Sakai, S. Tanaka, and M.P. Sheetz. 2006. Force Sensing by Mechanical Extension of the Src Family Kinase Substrate p130Cas. Cell. 127:1015-26.
Tamada, M., M.P. Sheetz, and Y. Sawada. 2004. Activation of a signaling cascade by cytoskeleton stretch. Dev Cell. 7:709-18.
Sawada, Y., and M.P. Sheetz. 2002. Force transduction by Triton cytoskeletons. J Cell Biol. 156:609-15.
Sawada, Y., K. Nakamura, K. Doi, K. Takeda, K. Tobiume, M. Saitoh, K. Morita, I. Komuro, K. De Vos, M. Sheetz, and H. Ichijo. 2001. Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase. J Cell Sci. 114:1221-7.