FY2020

Cell Signal Unit
Tadashi Yamamoto

(OIST Graduation Ceremony 2021.05.21)

Abstract

The Cell Signal Unit studies molecular and cellular events that are relevant to and important for maintaining healthy life in a variety of environmental conditions. Through the studies, Unit explores the cause of various diseases that include cancer, neuronal disorder, immunological diseases, diabetes/obesity, and defects in development at the molecular level. The Unit characterizes regulation of gene expression, particularly post-transcriptional regulation that includes regulation by microRNA, and long non-coding RNA and RNA binding proteins. The Unit also characterizes protein kinase-mediated cell signaling especially in the control of the brain function such as emotions, learning and memory.

1. Staff

  • Dr. Patrick Stoney, Staff Scientist
  • Dr. Ken Matsuura, Staff Scientist
  • Dr. Akiko Yanagiya, Staff Scientist
  • Dr. Shou Soeda, Postdoctoral Scholar
  • Dr. William Ashworth, Postdoctoral Scholar
  • Dr. Hiroaki Sako, Postdoctoral Scholar
  • Dr. Olga Elisseeva, Visiting Researcher
  • Dr. Guillaume Vares, Visiting Researcher
  • Ms. Saori Nishijima, Technical Staff
  • Ms. Risa Ishida, Technical Staff
  • Ms. Nao Ohmine, Technical Staff
  • Ms. Atsuko Sato, Technical Staff
  • Ms. Sandrine Anne Laure Burriel, Graduate Student
  • Mr. Shohei Takaoka, Graduate Student (JRF)
  • Mr. Hemanta Sarmah, Graduate Student (JRF)
  • Ms. Dina Mostafa, Graduate Student (JRF)
  • Mr. Mohieldin Magdy Mahmoud Youssef, Graduate Student
  • Mr. Hong Huat Hoh, Graduate Student
  • Ms. Aisulu Maipas, Graduate Student
  • Mr. Yuki Tara, Graduate Student
  • Mr. Haytham Mohamed Aly Mohamed, Graduate Student and Visiting researcher
  • Ms. Yuki Nakagawa, Research Unit Administrator

2. Collaborations

2.1 Physiology and Molecular Cellular Biology of the CCR4-NOT complex

  • Description: Analyze the physiological and molecular biological roles of each component of the CCR4-NOT complex using gene-modified mice.
  • Type of collaboration: Joint research
  • Researchers:
    • Dr. Keiji Kuba, Department of Physiology, Graduate School of Medicine, Akita University
    • Dr. Toru Suzuki, Laboratory of Immunogenetics, Riken Center for Integrative Medical Sciences
    • Dr. Toshinobu Fujiwara, Laboratory of Biochemistry, Faculty of Pharmacy, Kinki University
    • Dr. Masahiro Morita, Department of Molecular Medicine, UT Health
    • Dr. Nahum Sonenberg, Department of Biochemistry, McGill University

2.2 Basic cancer research for prevention and treatment

  • Description: Search for substances that contribute to the prevention and treatment of cancer from biological resources, and elucidate its mechanism of action
  • Type of collaboration: Joint research I and II
  • Researchers:
    • I. Representative director Kuniaki Nerome, Bioresource Laboratory LLC
    • II. Professor Shinya Ikematsu, National Institute of Technology, Okinawa College

2.3  Mechanisms and physiological roles of CCR4-NOT complex-regulated gene expression in the brain

  • Description: Electrophysiological studies of gene modified mice with abnormal social behavior
  • Type of collaboration: Joint research
  • Researchers:
    • Team leader Masaru Tamura, RIKEN

2.4 Analysis of CNOT9 function during mouse development by micro-CT imaging

  • Type of collaboration: Joint research
  • Researchers:
    • Team leader Masaru Tamura, RIKEN

2.5 Study of Cell-to-cell Interaction within Tumor Microenvironment Using An In-Vitro Three Dimensional Pancreatic Cancer Model

  • Description:
    • 1. Establishing an in vitro 3D organoid culture for pancreatic ductal adenocarcinoma to study cell-cell interaction within tumor microenvironment
    • 2. Investigating the origin of cancer stem cells in pancreatic ductal adenocarcinoma by live cell imaging using tumor organoid
    • 3. Characterizing the effects of the interaction between stromal cells and cancer stem cells
    • 4. Identifying the targets for tumor-stroma crosstalk and cancer stem cells
  • Type of collaboration: Joint research
  • Researchers:
    • Representative director Kuniaki Nerome, Bioresource Laboratory LLC
    • Professor Masafumi Nakamura, Assistant Professor Kenoki Ohuchida, Dr. Kazuhiro Koikawa, Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University

2.6 Human immune responses and their modulation in cancer and autoimmunity

  • Description: Human immune responses and their modulation in cancer and autoimmunity
  • Type of collaboration: Joint research
  • Researchers:
    • Research Scientist Olga Elisseeva, Laboratory of Immunogenetics, Riken Center for Integrative Medical Sciences

2.7 The neuromuscular junction as a new target for treatment of Hereditary Motor and Sensory Neuropathy, Okinawa-type, and related disorders

  • Description: Analyzing the pathogenic mechanism of HMSN-P using a mouse model; and analyzing the action mechanism(treatment mechanism) of enhancing NMJK formation on HMSN-P(HMSN with proximal dominancy)-like pathology, at the physiological, and molecular levels.
  • Type of collaboration: Joint research
  • Researchers: Professor Yuji Namanashi, the University of Tokyo.

3. Activities and Findings

 

4. Publications

4.1 Journals

  1. Akiyama T, Suzuki T, Yamamoto T.  RNA decay machinery safeguards immune cell development and immunological responses. Trends in Immunology, 2021 in press.
  2. Toru Suzuki, Shungo Adachi, Chisato Kikuguchi, Shinsuke Shibata, Saori Nishijima, Yurie Kawamoto, Yusuke Iizuka, Haruhiko Koseki, Hideyuki Okano, Tohru Natsume, Tadashi Yamamoto. Regulation of fetal genes by transitions among RNA-binding proteins during liver development. Int. J. Mol. Sci. 21(23), 9319, 2020.
  3. Ito-Kureha T, Miyao T, Nishijima S, Suzuki T, Kozumi S-I, Villar-Brioness A, Takahashi A, Akinama N, Morita M, Nagura I, Ishikawa H, Ichijo H, Akinama T*, Yamamoto T*. The CCR4-NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression. Nature Commun., 11(1):6169, 2020.
  4. Mostafa D, Yanagiya A, Georgiadou E, Wu Y, Stylianides T, Rutter GA, Suzuki T*, Yamamoto T*. Loss of β-cell identity and diabetic phenotype in mice caused by disruption of CNOT3-dependent mRNA deadenylation. Communications Biology, 3(1):476, 2020.
  5. Guillaume Vares, Vidhula Ahire, Shigeaki Sunada, Eun Ho Kim, Sei Sai, François Chevalier, Paul-Henri Romeo, Tadashi Yamamoto, Tetsuo Nakajima, Yannick Saintigny. A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells. Radiotherapy and Oncology, 150:253-261, 2020.
  6. Otsuka H, Fukao A, Tomohiro T, Adachi S, Suzuki T, Takahashi A, Funakami Y, Natsume T, Yamamoto T, Duncan K, Fujiwara T. ARE-binding Protein ZFP36L1 Interacts With CNOT1 to Directly Repress Translation via a Deadenylation-Independent Mechanism. Biochimie, 174:49-56, 2020.
  7. Sugawara S, Kanamaru Y, Sekine S, Maekawa L, Takahashi A, Yamamoto T, Watanabe K, Fujisawa T, Hattori K, Ichijo H. The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1. J Biol Chem, 295(17) 5588-5601, 2020.
  8. Takahashi A, Suzuki T, Soeda S, Takaoka S, Kobori S, Yamaguchi T, Mohamed H, Yanagiya A, Abe T, Shigeta M, Furuta Y, Kuba K, and Yamamoto T. The CCR4-NOT complex maintains liver homeostasis through mRNA deadenylation. Life Science Alliance, 3(5):e201900494, 2020.

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. K. Matsuura, H. M. A. Mohamed, A. Yanagiya, W. Ashworth and T. Yamamoto, The role of CCR4-NOT dependent post-transcriptional regulation in mammalian nervous system, the 43rd Annual Meeting of the Molecular Biology Society of Japan (MBSJ2020), Online (Kobe) 2020.12.02 2020
  2. P. Stoney, A. Yanagiya and T. Yamamoto, The CCR4-NOT subunits Cnot7 and Cnot8 regulate distinct mRNA targets, the 43rd Annual Meeting of the Molecular Biology Society of Japan (MBSJ2020) , Online (Kobe) 2020.12.02 FY2020
  3. A. Yanagiya, Translational control by poly(A)-binding protein in glucose-stimulated insulin biosynthesis in diabetes, the 43rd Annual Meeting of the Molecular Biology Society of Japan, Online (Kobe) 2020.12.02 2020

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

6.1 Seminar Title in Full

  1. "Cancer Cell Regulation by NF-kB" by Dr. Junichiro Inoue, RIKEN, 1 April 2020(online).
  2. "Dissecting the role of CNOT6L deadenylase in pressure overload-induced cardiac fibrosis" by Dr. Keiji Kuba, Akita University Graduate School of Medicine, October 5, 2020.
  3.  "4D chromatin dynamics in viral infection", by Dr. Yumiko Imai, National Institute Biomedical Innovation, Health and Nutrition (NIBIO), October 5, 2020.
  4. "YAP as a New Oncogene and a Mechanoresponder" by Dr. Marius Sudol, Icahn School of Medicine at Mount Sinai, 27 January 2021(online).
  5.  "Cell based high throughput screening systems toidentify bio-active compounds that target specific cellular targets" by Dr. Nobumoto Watanabe, RIKEN, 3 February 2021.
  6.  "RAF6 maintains mammary stem cells and promotespregnancy-induced epithelial cell expansion in mammary gland development" by Dr. Junichiro Inoue, RIKEN, 10 February 2021.
  7.  "Inhibition of T cell activation through PD-1/LAG-3micro-clusters and their modulation by checkpoint inhibitors" by Dr. Takashi Saito, RIKEN, on 24 Feb.
  8.  "Large-sale genetic analysis of various cancers forpersonalized medicine" by Dr. Yukihide Momozawa, RIKEN, 3 March 2021.
  9.  "Regulation of stress-induced apoptotic cell death bystress granule formation" by Dr. Mitsuhiro Takekawa, IMSUT, 10 March 2021(online).
  10.  "Metastasis of breast cancer" by Dr. Kentaro Semba, Waseda University, 17 March(online).
  11.  "How karyotypic evolution is controlled in cancerstem cells" by Dr. Toru Hirota, Japanese Foundation for Cancer Research, 24 March 2021.
  12.  "A new therapeutic strategy for resistant cancercells by enhancing ferroptosis" by Dr. Hideyuki Saya, Keio University, 31 March 2021.

7. Other

Nothing to report.