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Researcher Information

last modified:2017/09/21

Professor HANAYAMA Rikinari

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Faculty, Affiliation

Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences Professor, Department of Immunology
Director, Division of Immunology and Microbiome, Center of Advanced Preventive Medical Sciences

College and School Educational Field

Division of Medical Sciences, Graduate School of Medical Science
Division of Environmental Science, Graduate School of Medical Scienc
School of Medicine, College of Medical, Pharmaceutical and Health Sciences

Laboratory

Department of Immunology, Kanazawa University Graduate School of Medicine TEL:076-265-2727 FAX:076-265-2734

Academic Background

【Academic background(Doctoral/Master's Degree)】
Osaka University Doctor Graduate School of Medicine 200403 Completed
【Academic background(Bachelor's Degree)】
Osaka University Medical School 199903
【Degree】
MD, Ph.D (Advisor: Prof. Shigekazu Nagata)

Career

Osaka University Hospital Intern(1999/04-2000/03)
JSPS Research Fellow(2002/04-2004/03)
Osaka University Graduate School of Medicine, Department of Genetics Instructor(2004/04-2005/09)
Harvard Medical School Michael E. Greenberg Lab HFSP fellow(2005/09-2008/03)
Kyoto University Graduate School of Medicine, Department of Medical Chemistry Assistant Professor(2008/04-2011/10)
Osaka University Immunology Frontier Research Center(WPI-IFReC) Specially-appointed Associate Professor(2011/11-2015/05)
JST PRESTO Researcher(2012/11-2016/03)
MEXT Program Officer (KAKENHI)(2015/08-2017/07)
Kanazawa University Graduate School of Medicine, Department of Immunology Professor(2015/06-)
Kanazawa University Center of Advanced Preventive Medical Sciences, Division of Immunology and Microbiome Director(2017/04-)

Year & Month of Birth

1974/07

Academic Society

The Molecular Biology Society of Japan
The Japanese Biochemical Society
Japan Society for Immunology

Award

○Yamamura Award(1999/03)
○Yamamura Award(2004/03)
○GE & Science Prize for Young Life Scientists(2006/02)
○MEXT Young Scientist Prize(2009/04)
○HFSP Career Development Award(2011/04)
○Astellas Biomedical Award(2012/11)
○Osaka University Presidential Award(2014/07)
○Takeda Medical Research Grant(2016/11)

Specialities

Immunology、Pathological medical chemistry、Cell biology

Speciality Keywords

Exosome, Intercellular signal transduction, Neurodegenerative diseases, Phagocytes, Autoinflammation, Hemophagocytosis

Research Themes

Intercellular signal transduction by exosomes and its disorders

Intercellular signal transduction by exosomes and its disorders [Explanation of Figure]
Exosomes are generated inside intracellular compartments, called multivesicular endosomes (MVE), and are subsequently secreted by the fusion of MVE with cell plasma membrane. Exosomes carry various proteins, lipids, mRNAs and microRNAs derived from secretory cells and may participate in many aspects of immunity, aging, cancer and viral infection. However, the physiological functions of exosomes remain largely elusive. We therefore try to clarify the physiological and pathophysiological functions and in vivo dynamics of exosomes.

[Summary of Projects]
Our lab is aimed at clarifying the physiological functions of exosomes and their secretory mechanisms. Exosomes are secreted small membrane vesicles, composed of a lipid bilayer with inserted transmembrane proteins, enclosing cytosolic components derived from the exosome-producing cells. Recently, exosomes have received much attention as messengers of intercellular communication networks, allowing the exchange of proteins and lipids between the exosome-producing cells and target cells to trigger various cellular responses. Exosomes were also shown to carry mRNAs and microRNAs inside them, raising the possibility that exosomes transfer genetic information between cells. However, it is not clear whether these processes occur under physiological conditions. The only way to conclusively demonstrate the physiological roles for exosomes would be to specifically inhibit or increase their secretion in vivo, and demonstrate that this affects the physiological outcomes. Therefore, our research is currently aimed at addressing three basic questions:

1. What are the molecular mechanisms of exosome secretion?
2. What are the physiological functions of exosomes?
3. How do exosomes travel from secretory cells to the target cells in vivo?

It has recently been shown that several proteins which cause neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are transported via exosomes. We hope our research on exosomes will reveal avenues towards new therapeutic approaches against these diseases.

Autoinflammation caused by phagocytes

1) Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease caused by uncontrolled activation of lymphocytes and phagocytes. However, how hyper-inflammation induce hemophagocytosis by phagocytes remain completely unknown. We are trying to identify the molecular mechanisms regulating hemophagocytosis, hoping to clarify the pathophysiology of HLH that currently has no effective treatment.

2) During bacterial infection, phagocytes engulf bacteria into phagosomes and digest them by phagosome fusion with lysosomes. Indigestible debris inside phagolysosomes are expelled from the phagocytes when phagolysosomes fuse with the plasma membrane. During this process, digestive enzymes are also released from phagolysosomes, thereby degrading surrounding tissues. However, the molecular mechanisms regulating these events are poorly understood. We are trying to clarify the molecular mechanisms of lysosomal exocytosis by phagocytes, hoping to provide new insights into chronic inflammatory mechanisms.

Education policy

We will provide students with basic to advanced techniques and knowledge on life science research. Students will learn various techniques on molecular biology as well as cell biology by addressing above projects. We will also teach how to evaluate scientific papers properly. We welcome anybody with high motivation.

Books

Papers

  •  High purity isolation and sensitive quantification of extracellular vesicles using affinity to TIM4. Yoshida T, Ishidome T, Hanayama R. Curr Protoc Cell Biol. in press 2017
  •  Induction of live cell phagocytosis by a specific combination of inflammatory stimuli. Ishidome T, Yoshida T, Hanayama R. EBioMedicine 22 89-99 2017
  •  MiR-21-5p in urinary extracellular vesicles is a novel biomarker of urothelial carcinoma. Matsuzaki K, Fujita K, Jingushi K, Kawashima A, Ujike T, Nagahara A, Ueda Y, Tanigawa G, Yoshioka I, Ueda K,Hanayama R, Uemura M, Miyagawa Y, Tsujikawa K, Nonomura N. Oncotarget 8 15 24668-78 2017
  •  A novel affinity-based method for the isolation of highly purified extracellular vesicles. Nakai Y, Yoshida T, Diez D, Miyatake Y, Nishibu T, Imawaka N, Naruse K, Sadamura Y, Hanayama R Sci Rep 6 33935 2016
  •  Mechanisms of lysosomal exocytosis by immune cells. Song J, Hanayama R Chronic Inflammation Miyasaka M. and Takatsu K. eds. 369-375 2016

show all

  •  Neuronal exosomes facilitate synaptic pruning by up-regulating complement factors in microglia. Bahrini I, Song J, Diez D, Hanayama R Sci Rep 5 7989 2015
  •  Autoimmune Diseases and the Role of MFG-E8. Hanayama R MFG-E8 and Inflammation Wang P. ed. 97-117 2014
  •  Two-step engulfment of apoptotic cells. Toda S, Hanayama R, Nagata S Mol Cell Biol 32 1 118-25 2012
  •  The Angelman syndrome protein Ube3A regulates synapse development by ubiquitinating Arc. Greer PL, Hanayama R (co-first authors), Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Kim TK, Griffith EC, Waldon Z, Maehr R, Ploegh HL, Chowdfury S, Worley PF, Steen J, Greenberg ME Cell 140 5 704-16 2010
  •  Autoimmunity and the clearance of dead cells. Nagata S, Hanayama R, Kawane K Cell 140 5 619-30 2010
  •  Engulfment of apoptotic cells and its physiological roles. Hanayama R, Miyanishi M, Yamaguchi H, Suzuki J, Nagata S Cell Death Melino G. and Vaux D. eds. 165-75 2009
  •  Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8. Hanayama R, Nagata S Proc Natl Acad Sci USA 102 16886-91 2005
  •  Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Hanayama R, Tanaka M, Miyasaka K, Aozasa K, Koike M, Uchiyama Y, Nagata S Science 304 1147-50 2004
  •  Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells. Hanayama R, Tanaka M, Miwa K, Nagata S J Immunol 172 6 3876-82 2004
  •  Identification of a factor that links apoptotic cells to phagocytes. Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S Nature 417 182-7 2002

Conference Presentations

Arts and Fieldwork

Patent

Theme to the desired joint research

○Development of methods to purify, detect, quantify exosomes
○Elucidation of physiological and pathophysiological functions of exosomes
○Development of in vivo imaging techniques of exosomes
○Create new drugs using or targeting exosomes
○Development of new drugs for hemophagocytosis
○Development of new drugs that prevent tissue damages by heterolysis

Grant-in-Aid for Scientific Research

○MEXT Grants-in-Aid「Challenging Exploratory Research」(2016-2017) 
○AMED Grants-in-Aid「Intractable Disease」(2016-2018) 
○MEXT Grants-in-Aid「Young Scientist(A)」(2013-2016) 
○JST PRESTO「Chronic inflammation」(2012-2015) 
○AMED Grants-in-Aid「Innovative Cancer」(2014-2016) 
○MEXT Grants-in-Aid「Brain Environment」(2012-2013) 
○MEXT Grants-in-Aid「Young Scientist(B)」(2010-2012) 
○MHLW Grants-in-Aid「Hepatitis」(2012-2014) 
○MEXT Grants-in-Aid「Brain Environment」(2014-2015) 

Classes (Bachelors)

○Immunology(2017)
○Fundamental Immunology(2017)
○Presentation and Debate (Freshman Seminar II)(2017)

Classes (Graduate Schools)

○Immunology(2017)
○Basic Preventive Medicine(2017)
○Introduction to Basic Medical Science(2017)
○Introduction to Basic Medical Science(2017)

International Project

International Students

Lecture themes

Others (Social Activities)

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