MM family laboratories


This page introduces the achievement of our alumni, who operate their laboratories or companies, in descending order by year.
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Masahiro Kitano, Ph.D.
Ikasu Brewing
As a graduate student, Masahiro Kitano developed the FRET biosensor for Rab5 and discovered the phenomenon of Rab5 activity flashing on phagosomes during phagocytosis. He moved to the U.S. and, after a post-doctoral fellowship, started a barley wine brewing company.
  • Former graduate student
  • Kitano M et al. Imaging of Rab5 activity identifies essential regulators for phagosome maturation. Nature. 453(7192):241-5. 2008
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Yumi Konagaya, Ph.D.
Laboratory for Quantitative Biology of Cell Fate Decision, BDR, RIKEN
As a graduate student, Yumi Konagaya developed a FRET biosensor for AMPK, created transgenic mice expressing it, and revealed differences in AMPK activation kinetics in mouse slow and fast muscle. After studying in the U.S., she returned to Japan as a team leader at RIKEN.
  • Former graduate student
  • Konagaya Y et al. A Highly Sensitive FRET Biosensor for AMPK Exhibits Heterogeneous AMPK Responses among Cells and Organs. Cell Rep 21: 2628-2638, 2017
  • Konagaya Y et al. Intravital imaging reveals cell cycle-dependent myogenic cell migration during muscle regeneration. Cell cycle 19: 3167-3181, 2020
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Kenta Terai, M.D., Ph.D.
Anatomy and Cell Biology, Tokushima University Faculty of Medicine
Dr. Kenta Terai developed FRET biosensors of Raf as a graduate student, then studied in the United States as a postdoc, and served as an assistant professor at the University of Tokyo before moving to our laboratory as an associate professor. He supervised many graduate and medical students in biosensor development and live imaging research.
  • Former Associate Professor at Kyoto University
  • Matsuda K et al. Knockout of all ErbB-family genes delineates their roles in proliferation, survival and migration. J Cell Sci. 136(16):jcs261199. 2023
  • Kinjo T et al. FRET-assisted photoactivation of flavoproteins for in vivo two-photon optogenetics. Nat Methods. 16(10):1029-1036. 2019
  • Terai K, Matsuda M. The amino-terminal B-Raf-specific region mediates calcium-dependent homo- and hetero-dimerization of Raf.EMBO J. 9;25(15):3556-64. 2006
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Tsuyoshi Hirashima, Ph.D.
Mechanobiology Institute, NUS
Dr. Takeshi Hirashima was the group leader of the Mechanobiology team and supervised many students. His research focused on cell motility and tissue/organ morphogenesis in terms of both force and intracellular signaling, using mathematical modeling and imaging. He was one of the founding members of the Life Dynamics and Systems Science Project.
  • Former Research Lecturer at Kyoto University
  • Yoshida et al. Incoherent Feedforward Regulation via Sox9 and ERK Underpins Mouse Tracheal Cartilage Development. Frontiers in cell and developmental biology 8, 585640, 2020
  • Boocock et al. Theory of mechanochemical patterning and optimal migration in cell monolayers. Nat Phys 10.1038/s41567-020-01037-7, 2020
  • Hino et al. ERK-mediated mechanochemical waves direct collective cell polarization. Dev Cell 53, 646-660, 2020
  • Ihermann-Hella et al., Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation. Stem Cell Reports 11, 912-928, 2018
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Hiroshi Nishihara, M.D., Ph.D.
Genomics unit, Keio Cancer Center, Keio University School of Medicine
Dr. Takeshi Hirashima was the group leader of the Mechanobiology team and supervised many students. His research focused on cell motility and tissue/organ morphogenesis in terms of both force and intracellular signaling, using mathematical modeling and imaging. He was one of the founding members of the Life Dynamics and Systems Science Project.
  • Former Graduate student
  • Nishihara et al. Non-adherent cell-specific expression of DOCK2, a member of the human CDM-family proteins. Biochim. Biophys. Acta. 1452:179-187, 1999.
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Masamichi Imajo, Ph.D.
Institute for Chemical Reaction Design and Discovery
As the leader of the intestinal group, Dr. Masamichi Imashiro menotored many graduate students. In particular, he studied how the activity of ERK map kinase is involved in the development of intestinal tumors.
  • Former assistant professor at Kyoto University
  • Okuchi et al. Identification of aging-associated gene expression signatures that precede intestinal tumorigenesis. PLoS One 11, e0162300, 2016. doi:10.1371/journal.pone.0162300
  • Muta et al. Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine. Nat Commun 9, 2174, 2018. doi:10.1038/s41467-018-04527-8
  • Muta et al. Dynamic ERK signaling regulation in intestinal tumorigenesis. Molecular and cellular oncology 5, e1506684, 2018. doi:10.1080/23723556.2018.1506684
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Aryé Elfenbein, M.D., Ph.D.
Wild Type
Dr. Aryé Elfenbein is an MD PhD student at Dartmouth Medical School, Kyoto University, where he conducted research in collaboration with Marc Simons' lab on the mechanism of FGFR receptor activation by Syndecan 4 and Rho family G protein imaging. After completing his internship and postdoctoral fellowship, he started his own company, Wild Type.
  • Fomer MD PhD student
  • Elfenbein et al. Syndecan 4 regulates FGFR1 signaling in endothelial cells by directing macropinocytosis. Sci Signal 5, ra36 (2012).
  • Elfenbein et al. Suppression of RhoG activity is mediated by a syndecan 4.synectin.RhoGDI1 complex and is reversed by PKCalpha in a Rac1 activation pathway. J Cell Biol 186, 75-83, 2009.
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Eishu Hirata, M.D., Ph.D.
Cancer Research Institute, Kanazawa University
Division of Tumor Cell Biology and Bioimaging
Dr. Eishu Hirata performed intravital imaging of brain tumors and showed that the activity of low molecular weight G protein was high in the periphery of the tumor. He then studied at the UK Cancer Institute and used the FRET biosensor of ERK to show that anticancer drug resistance mechanisms are induced by interactions with surrounding tissues.
  • Former assistant professor
  • Hirata et al. In vivo fluorescence resonance energy transfer imaging reveals differential activation of Rho-family GTPases in glioblastoma cell invasion J. Cell Sci. 125, 858-868, 2012.
  • Hirata et al. Intravital imaging reveals how BRAF inhibition generates drug-tolerant microenvironments with high integrin beta1/FAK signaling. Cancer cell 27, 574-588, 2015.
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Kazuhiro Aoki, Ph.D.
National Institute for Basic Iology
Division of Quantitative Biology
Kazuhiro Aoki advanced FRET imaging in neurons when he was a graduate student, and systems biology of oncogene signaling systems when hewas a faculty member. He was the core member of the imaging-based quantitative biology and systems biology.
  • Former associate professor
  • Aoki et al. Stochastic ERK activation induced by noise and cell-to-cell propagation regulates cell density-dependent proliferation. Molecular Cell 52: 529-540, 2013.
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Yusuke Ohba, M.D., Ph.D.
Hokkaido University Graduate School of Medicine
Department of Cell Physiology
Dr. Yusuke Ohba created knockout mice of C3G and showed that the loss of this molecule induces embryonic lethality and that this molecule is required for cell adhesion. He also created a simulation model to analyze how Ras and Rap1 are spatiotemporally analyzed by using the Raichu biosensor.
  • Former assistant professor
  • Ohba et al. Mechanism of the spatio-temporal regulation of Ras and Rap1. EMBO J. 22:859-869.2003.
  • Ohba et al. Requirement of C3G-dependent Rap1 activation for cell adhesion and embryogenesis. EMBO J. 20:3333-3341, 2001
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Etsuko Kiyokawa, M.D., Ph.D.
Kanazawa Medical University
Department of Pathology I
Dr. Etsuko Kiyokawa analyzed the relationship between the low molecular weight GTPase Rac1 and DOCK180 to clarify how DOCK180 induces lamellipoidal protrusion. During this process, she found that DOCK180 specifically binds to a dominant negative mutant of Rac1. Since dominant negative mutants of low molecular weight GTPases were known to bind to their activators, she proposed that DOCK180 is a novel activator of Rac1.
  • Former research lecturer
  • Kiyokawa et al. Activation of Rac1 by a Crk SH3-binding protein, DOCK180. Genes Dev 12:3331-3336, 1998
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Takeshi Nakamura, Ph.D.
Tokyo University of Science
Research Institute for Biomedical Sciencess
Dr. Takeshi Nakamura led his graduate students to establish imaging techniques in neurons. He created a biosensor for Rab5 and clarified the mechanism of Rab5 activation during phagocytosis of apoptotic cells.
  • Former research lecturer
  • Kitano et al. Imaging of Rab5 activity identifies essential regulators for phagosome maturation. Nature 453(7192):241-5, 2008
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Hideki Hasegawa, M.D., Ph.D.
National Institute of Infectious Diseases
Influenza Research Center
Dr. Hideki Hasegawa identifed the 180 kDa Crk binding protein. At that time, isolating a cDNA longer than 5 kb was challenging, causing him to spend much time to determine the cDNA sequence at the 5' end. Using a cDNA library prepared by Prof. Nojima at Osaka University, he finally succeeded to determine the full length cDNA sequence and named the protein DOCK180. Expression of DOCK180 on the plasma membrane induces lamellipodia formation and cooperates with the low molecular weight G protein Rac1. However, DOCK180 shared little homology with known proteins, and the analysis of its biochemical function awaited the next study.
  • Former graduate student
  • Hasegawa et al. DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane. Mol Cell Biol 16:1770-1776, 1996
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Shinya Tanaka, M.D., Ph.D.
Hokkaido University Graduate School of Medicine
Department of Cancer Pathology
In 1990's, protein-protein interactions were extensively studied to identify new signaling molecules. Dr. Shinya Tanaka developed the Far Western method and found that proteins of 130 kDa and 180 kDa bind to the Crk oncogene product. He further applied this method to the screening of phage expression libraries to isolate the cDNA of the 130 kDa molecule, and discovered that the protein encoded by the cDNA is a novel Ras family G-protein activator, which he named C3G. Later, Dr. Seisuke Hattori and his colleagues clarified that this molecule is an activator of Rap1, one of the Ras family molecules.
  • Former graduate student
  • Tanaka S et al. C3G, a guanine nucleotide releasing protein, binds to the SH3 domains of CRK and ASH/GRB2. Proc Natl Acad Soc USA 91:3443-3447, 1994
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Naoki Mochizuki, M.D., Ph.D.
National Cerebral and Cardiovascular Center
Research Institute
During the process of studying the regulatory mechanism of trimeric G proteins, Dr. Naoki Mochizuki discovered that Gi family proteins bind to the splicing variant of Rap1GAP, an inactivator of Rap1, and named this molecule Rap1GAPII. He also developed a FRET-based biosensor, Raichu, to observe the activity of these Ras family low molecular weight G proteins in live cells.
  • Former team leader
  • Mochizuki et al. Activation of ERK/MAPK pathway by an isoform of rap1GAP associated with Gai. Nature 400:891-894, 1999
  • Mochizuki et al. Spacio-temporal images of growth factor-induced activation of Ras and Rap1. Nature 411:1065-1068, 2001

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