Biomedical Research Activities

University of Tsukuba

CONTENTS

Research Fields

PI

page

University of Tsukuba
Molecular Cell Biology

Irie K

1

Gene Regulation

Hisatake K

2

Cellular Reprogramming and Biotechnology

Nishimura K

3

Physiological Chemistry

Ohbayashi N

4

Molecular Neurobiology

Masu M

5

Anatomy and Embryology

Takahashi S

6

Laboratory Animal Science

Sugiyama F

7

Experimental Pathology

Kato M

8

Diagnostic Surgical Pathology

Noguchi M

9Kidney and Vascular Pathology

Nagata M

10

Immunology

Shibuya A

11Regenerative Medicine and Stem Cell Biology

Ohneda O

12

Biomedical Engineering

Miyoshi H

13

Infection Biology

Kawaguchi A

14

Microbiology

Morikawa K

15

Molecular Parasitology

Ho K

16

Neurophysiology

Koganezawa T

17

Cognitive and Behavioral Neuroscience

Matsumoto M

18

Radiation Biology

Tsuboi K

19

Vascular Matrix Biology

Yanagisawa H

20

Molecular and Genetic Epidemiology

Tsuchiya N

21

Public Health Medicine

Yamagishi K

22

Environmental Medicine

Kumagai Y

23

Longevity medicine Endowed Chair #2

Matsuzaki I

24

Molecular and Developmental Biology

Kobayashi M

25

Occupational Psychiatry / Space Medicine #1

CONTENTS

Research Fields

PI

page

University of Tsukuba
Medical Genetics

Noguchi E

26

Legal Medicine

Honda K

27

Genome Biology

Muratani M

28

Behavioral Neuroscience

Yanagisawa M

29

Functional neuroanatomy

Funato H

30

Medicinal Chemistry, Organic Chemistry

Nagase H
Kutsumura N

31

Biochemistry and Molecular Genetics

Liu Q

32

Manipulation of memory during sleep

Sakaguchi M

33

Systems Sleep Biology

Lazarus M

34

Molecular Sleep Biology

Urade Y

35

Sleep Neuroscience

Vogt Kaspar

36

Brain maturation / evolution

Hayashi Y

37

Molecular Behavioral Physiology

Sakurai T

38

Research Fields

PI

page

Cooperative Graduate Programs
Functional Genomics

Ishii S

39

Experimental Hematology

Nakamura Y

40

Biochemistry and Molecular Cell Biology

Tanaka K

41

International Medicine

Kano S

42

Virology

Kurane I

43

Irie. K

Molecular Cell Biology
Principal Investigator Kenji Irie
E-mail address kirie@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/public/basic-med/    molcellbiol/index.html
Other Faculty Members
Assistant Professor Tomoaki Mizuno: mizuno@md.tsukuba.ac.jp
Assistant Professor Yasuyuki Suda: ysuda@md.tsukuba.ac.jp

Major Scientific Interests of the Group
Post-transcriptional regulation of gene expression by RNA-binding proteins
Molecular mechanism of mRNA localization and local translation regulating cell polarity, asymmetriccell division, and cell-fate
Regulation of the endoplasmic reticulum stress response by protein kinases
Projects for Regular Students in Doctoral or Master’s Programs
1) Post-transcriptional regulation of gene expression by the Ccr4-Not complex in yeast.
2) Regulation of the endoplasmic reticulum stress response by protein kinases.
3) Roles of yeast Ataxin-2 ortholog, Pbp1, in the control of mRNA stability and translation.
4) Roles of  decapping activators in the control of mRNA stability and translation.
Study Programs for Short Stay Students (one week ~ one trimester)
1) Yeast genetic approaches including the isolation and characterization of mutants, tetrad analysis,complementation, and mitotic recombination.
2) Molecular genetic techniques including yeast transformation, gene knockout, and generation of
mutations in cloned genes.
3) Molecular biology and biochemistry techniques analyzing gene expression including Northernblotting, RT-PCR, and Western blotting.
4) Imaging yeast cells using indirect immunofluorescence and GFP-protein fusions.
Recent Publications
1) Duy DL, Suda Y, Irie K.   Cytoplasmic Deadenylase Ccr4 is Required for Translational Repression of
LRG1 mRNA in the Stationary Phase. PLoS One. 2017 Feb 23;12(2):e0172476.
2) Ito Y, Kitagawa T, Yamanishi M, Katahira S, Izawa S, Irie K, Furutani-Seiki M, Matsuyama T.
Enhancement of protein production via the strong DIT1 terminator and two RNA-binding proteins in
Saccharomyces cerevisiae. Sci Rep. 2016 Nov 15;6:36997.
3) Lien PT, Izumikawa K, Muroi K, Irie K, Suda Y, Irie K. Analysis of the Physiological Activities of Scd6
through Its Interaction with Hmt1.. PLoS One. 2016 Oct 24;11(10):e0164773.
4) Li X, Ohmori T, Irie K, Kimura Y, Suda Y, Mizuno T, Irie K. Different Regulations of ROM2 and LRG1
Expression by Ccr4, Pop2, and Dhh1 in the Saccharomyces cerevisiae Cell Wall Integrity Pathway.
mSphere. 2016 Sep 28;1(5).
5) Mizuno T, Masuda Y, Irie K. The Saccharomyces cerevisiae AMPK, Snf1, Negatively Regulates the
Hog1 MAPK Pathway in ER Stress Response. PLoS Genet. 2015 Sep 22;11(9):e1005491.
6) Kimura Y, Irie K, Irie K. Pbp1 is involved in Ccr4- and Khd1-mediated regulation of cell growth throughassociation with ribosomal proteins Rpl12a and Rpl12b. Eukaryot Cell. 2013 Jun;12(6):864-74.

1

Hisatake. K

Gene Regulation
Principal Investigator Koji Hisatake
E-mail address kojihisa@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/basic-med/biochem/gene/
Other Faculty Members
Associate Professor Aya Fukuda: fukudaa@md.tsukuba.ac.jp
Assistant Professor Ken Nishimura: ken-nishimura@md.tsukuba.ac.jp
Assistant Professor Yohei Hayashi: yohei.hayashi@md.tsukuba.ac.jp

Major Scientific Interests of the GroupOur group studies the regulation of eukaryotic gene expression, focusing on how transcription
regulates cell differentiation and reprogramming.   In particular, we focus on the studies about theroles of transcription factors and epigenetic changes in regulating iPS cell generation and adipocyte
differentiation.  We also develop modified vectors and transcription factors to enhance reprogrammingand differentiation.
Projects for Regular Students in Doctoral or Master’s Programs
1) Mechanistic analyses of the roles for Oct4, Sox2, Klf4 and c-myc during iPS cell generation.
2) Generation of transcription factors with an enhanced reprogramming ability.
3) Analyses of epigenetic mechanisms of iPS cell generation.
4) Efficient differentiation of iPS cells into neurons.
5) Identification and functional analyses of transcription factors involved in adipocyte commitment.
Study Programs for Short Stay Students (one week ~ one trimester)1) Analysis of transcriptional regulation during white and brown adipocyte differentiation.
2) Generation of iPS cells using a Sendai virus-based vector.
Recent Publications
1) Nishimura K, Aizawa S, Nugroho FL, Shiomitsu E, Yen THH, Linh BP, Borisova DE, Sakuragi
Y, Takada H, Kurisaki A, Hayashi Y, Fukuda A, Nakanishi M, Hisatake K. A Role for KLF4 in
Promoting the Metabolic Shift via TCL1 during Induced Pluripotent Stem Cell Generation. Stem Cell
Reports, 2017 (in press)
2) Hayashi Y, Hsiao EC, Sami S, Lancero M, Schlieve CR, Nguyen T, Yano K, Nagahashi A, Ikeya M,
Matsumoto Y, Nishimura K, Fukuda A, Hisatake K, Tomoda K, Asaka I, Toguchida J, Conklin BR,
Yamanaka Y. BMP-SMAD-ID Promotes Reprogramming to Pluripotency by Inhibiting p16/INK4ADependent Senescence. Proc Natl Acad Sci USA 113(46), 13057-13062, 2016
3) Nakadai T, Fukuda A, Shimada M, Nishimura K, Hisatake K. The RNA-binding Complexes, NF45NF90 and NF45-NF110, Associate Dynamically with the c-fos Gene and Function as Transcriptional
Coactivators. J Biol Chem 290(44), 26832-26845, 20154) Nishimura K, Kato T, Chen C, Oinam L, Shiomitsu E, Ayakawa D, Ohtaka M, Fukuda A, Nakanishi
M, Hisatake K. Manipulation of KLF4 Expression Generates iPSCs Paused at Successive Stages of
Reprogramming. Stem Cell Reports 3(5), 915-929, 2014
5) Fu k ud a A, Sh i ma d a M, Na k a d ai T, Nish i mu r a K , H isat ake K . Heterogeneou s Nuclea r
Ribonucleoprotein R Cooperates with Mediator to Facilitate Transcription Reinitiation on the c-Fos
Gene. PLoS ONE 8(8): e72496. doi:10.1371/journal.pone.0072496, 20132

Nishimura. K

Cellular Reprogramming andBiotechnology
Principal Investigator Ken Nishimura
E-mail address ken-nishimura@md.tsukuba.ac.jp
URL http://ttweb.sec.tsukuba.ac.jp/nishimura.html

Major Scientific Interests of the GroupOur group studies the molecular mechanism of the cell reprogramming to establish an efficientmethod of the production of well-reprogrammed iPS cells by using our unique gene transfer system(SeVdp vectors).  We are also trying to apply these vector to establish safe cell-differentiation systems.
Projects for Regular Students in Doctoral or Master’s Programs
1) Molecular mechanism of iPS cell production by analyzing series of partially reprogrammed cells
induced by SeVdp vectors.
2) Establishment of iPS cell production methods with novel factors which improve cell reprogramming.
3) Development of SeVdp vector-based methods to produce differentiated tissues without contaminating
undifferentiated cells.
Study Programs for Short Stay Students (one week ~ one trimester)1) Production of mouse and human iPS cells using SeVdp vectors.
2) Cell biology and molecular biology experiments for analysis of gene expression.
Recent Publications
1) Nishimura K, Aizawa S, Nugroho FL, Shiomitsu E, Tran YTH, Bui PL, Borisova E, Sakuragi

Y, Takada H, Kurisaki A, Hayashi Y, Fukuda A, Nakanishi M, Hisatake K: A role for KLF4 inpromoting the metabolic shift via TCL1 during induced pluripotent stem cell generation. Stem Cell
Reports, 2017 in press
2) Bueno C, Sardina JL, Di Stefano B, Romero-Moya D, Muñoz-López A, Ariza L, Chillón MC,
Balanzategui A, Castaño J, Herreros A, Fraga MF, Fernández A, Granada I, Quintana-Bustamante O,
Segovia JC, Nishimura K, Ohtaka M, Nakanishi M, Graf T, Menendez P: Reprogramming human
B cells into induced pluripotent stem cells and its enhancement by C/EBPα. Leukemia, 30: 674-682,
20163) Nishimura K, Kato T, Chen C, Oinam L, Shiomitsu E, Ayakawa D, Ohtaka M, Fukuda A, Nakanishi
M, Hisatake K: Manipulation of KLF4 expression generates iPSCs paused at successive stages ofreprogramming. Stem Cell Reports, 3: 915-929, 20144) Nishimura T, Kaneko S, Kawana-Tachikawa A, Tajima Y, Goto H, Zhu D, Nakayama-Hosoya K,
Iriguchi S, Uemura Y, Shimizu T, Takayama N, Yamada D, Nishimura K, Ohtaka M, Watanabe N,
Takahashi S, Iwamoto A, Koseki H, Nakanishi M, Eto K, Nakauchi H: Generation of rejuvenatedantigen-specific T cells by reprogramming to pluripotency and redifferentiation.  Cell Stem Cell, 12:
114-126, 20135) Nishimura K, Sano M, Ohtaka M, Furuta B, Umemura Y, Nakajima Y, Ikehara Y, Kobayashi T,
Segawa H, Takayasu S, Sato H, Motomura K, Uchida E, Kanayasu-Toyoda T, Asashima M, Nakauchi
H, Yamaguchi T, Nakanishi M: Development of Defective and Persistent Sendai Virus Vector: aUnique Gene Delivery/Expression System Ideal for Cell Reprogramming. J. Biol. Chem., 286: 47604771, 20113

Ohbayashi.N

Physiological ChemistryPrincipal Investigator Norihiko Ohbayashi
E-mail address nohbayashi@md.tsukuba.ac.jp
URL http:  //www.md.tsukuba.ac.jp/basic-med/biochem/kanaholab/index.html  
Other Faculty Members
Professor Yasunori Kanaho: ykanaho@md.tsukuba.ac.jp
Assistant Professor Yuji Funakoshi: funa@md.tsukuba.ac.jp
Assistant Professor Naohiro Katagiri: nkatagiri@md.tsukuba.ac.jp
Assistant Professor Tsunaki Hongu: thongu@md.tsukuba.ac.jp

Major Scientific Interests of the Group
Studies on regulatory mechanisms and physiological functions of membrane trafficking systems
through small GTP-binding proteins such as Rab and Arf.
Projects for Regular Students in Doctoral or Master’s Programs
1) Physiological functions of the small GTP-binding proteins (Rabs and Arf6) and their regulators intumorigenesis/metastasis, morphogenesis, and neural plasticity.
2) Regulatory mechanisms of ubiquitylation of cargo proteins in the recycling system.
3) Molecular mechanisms of biogenesis of melanin-containing organelles though Rab small GTP-binding
proteins.
4) Development of specific agonists/antagonists for certain small GTP-binding proteins.
Study Programs for Short Stay Students (one week ~ one trimester)1) Enzyme assay and imaging of molecules regulating membrane trafficking systems.
2) Assays for cell functions such as cell proliferation, cell motility, focal adhesion, secretion,
endocytosis, exocytosis, recycling, etc.
Recent Publications
1) Marubashi S, Shimada H, Fukuda M, Ohbayashi N. RUTBC1 Functions as a GTPase-activating
Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes. J Biol Chem.
291, 1427-40, (2016).
2) Miura Y, Hongu T, Yamauchi Y, Funakoshi Y, Katagiri N, Ohbayashi N, Kanaho Y. ACAP3
regulates neurite outgrowth through its GAP activity specific to Arf6 in mouse hippocampal neurons.
Biochem J. 473, 2591-602, (2016).
3) Marubashi S, Ohbayashi N, Fukuda M. A Varp-Binding Protein, RACK1, Regulates Dendrite
Outgrowth through Stabilization of Varp Protein in Mouse Melanocytes. J Invest Dermatol. 136,
1672-80, (2016).
4) Okada R, Yamauchi Y, Hongu T, Funakoshi Y, Ohbayashi N, Hasegawa H, Kanaho Y. Activationof the Small G Protein Arf6 by Dynamin2 through Guanine Nucleotide Exchange Factors in
Endocytosis. Sci Rep. 27, 14919, (2015).
5) Yatsu A, Shimada H, Ohbayashi N, Fukuda M. Rab40C is a novel Varp-binding protein that promotes
proteasomal degradation of Varp in melanocytes. Biol Open. 4, 267-75, (2015).
6) Hongu T, Funakoshi Y, Fukuhara S, Suzuki T, Sakimoto S, Takakura N, Ema M, Takahashi S, Itoh
S, Kato M, Hasegawa H, Mochizuki N, Kanaho Y. Arf6 regulates tumour angiogenesis and growththrough HGF-induced endothelial β1 integrin recycling. Nat Commun. 6, 7925, (2015).
7) Ishida M, Ohbayashi N, Fukuda M. Rab1A regulates anterograde melanosome transport by recruitingkinesin-1 to melanosomes through interaction with SKIP. Sci Rep. 5, 8238, (2015).
8) Funakoshi Y, Chou MM, Kanaho Y, Donaldson JG. TRE17/USP6 regulates ubiquitylation andtrafficking of cargo proteins that enter cells by clathrin-independent endocytosis. J Cell Sci. 127,
4750-61, (2014).

4

Masu. M

Molecular Neurobiology
Principal Investigator Prof. Masayuki Masu
E-mail address mmasu@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/duo/molneurobiol/
Other Faculty Members
Lecturer: Kensuke Shiomi: kshiomi@md.tsukuba.ac.jp
Lecturer: Kazuko Keino-Masu: kazumasu@md.tsukuba.ac.jp
Assistant Professor: Takuya Okada: okada.takuya.gw@u.tsukuba.ac.jp

Major Scientific Interests of the GroupOur main research focus is to study the molecular mechanisms that regulate the neural circuit
formation and higher brain functions. Using integrative approaches including molecular biology,
biochemistry, pharmacology, developmental biology, and neuroanatomy, we have been investigating
how complex networks are formed in the developing brain and how the mature brain functions are
acquired and regulated. We are particularly interested in the molecules that play a role in neuraldifferentiation, cell migration, axon guidance, and synaptogenesis.
Projects for Regular Students in Doctoral or Master’s Programs
1) Molecular study on neural differentiation
2) Molecular study on axon guidance3) Molecular study on neural cell migration
Training Programs for Short Stay Students (one week ~ one trimester)1) Immunohistochemistry2) In situ hybridization
3) 3D brain imaging
Recent Publications
1) Masu M. Proteoglycans and axon guidance: a new relationship between old partners. J Neurochem
139: 58-75, 2016.
2) Takashima Y, Keino-Masu K, Yashiro H, Hara S, Suzuki T, van Kuppevelt TH, Masu M, andNagata M. Heparan Sulfate 6-O-EndoSulfatases, Sulf1 and Sulf2, Regulate Glomerular Integrity by
Modulating Growth Factor Signaling. Am J Physiol Renal Physiol 310: F395-408, 2016.
3) Freeman SD, Keino-Masu K, Masu M, and Ladher R K. Expression of the heparan sulfate
6-O-endosulfatases, Sulf1 and Sul2, in the avian and mammalian inner ear suggests a role forsulfation in inner ear development. Dev Dyn 244: 168-180, 2015.
4) Nagamine S et al. Organ-Specific Sulfation Patterns of Heparan Sulfate Generated by ExtracellularSulfatases Sulf1 and Sulf2 in Mice. J Biol Chem 287: 9579-9590, 2012.
5) Okada T, Keino-Masu K, and Masu, M. Migration and nucleogenesis of mouse precerebellar neurons
visualized by in utero electroporation of a green fluorescent protein gene. Neurosci Res 57: 40-49,
2007.
6) Keino-Masu K, Masu M, et al. Deleted in Colorectal Cancer (DCC) Encodes a Netrin Receptor. Cell
87: 175-185, 1996

5

Takahashi.S

Anatomy and Embryology
Laboratory Animal Resource Center
Principal Investigator
E-mail address
URL

Satoru Takahashi

satoruta@md.tsukuba.ac.jp

http://www.md.tsukuba.ac.jp/basic-med/
anatomy/embryology/index.html

Major Scientific Interests of the GroupWe are working on the functional analysis of transcription factors in the body by employing
developmental engineering techniques such as the generation of transgenic mice.
Projects for Regular Students in Doctoral or Master’s Programs
1) Molecular mechanism of the development of pancreatic endocrine cells and macrophages.   Weare researching the molecular mechanisms of the development of pancreatic endocrine cells andmacrophages.   By analyzing the function of the large Maf family of transcription factors.   In bothhuman and mouse, four large Maf transcription factors, MafA, Maf B, c-Maf and Nrl, have been
identified.
2) Analysis about in vivo functions of sugar chains on molecules.  In addition to these themes, we arealso analyzing functions of sugar chains on molecules in vivo by using genetically manipulated mice.
Study Programs for Short Stay Students (one week ~ one trimester)1) Histological analysis of genetically manipulated mice.
2) Handling skill for mouse embryos.
Recent Publications
1) Shichita T, Ito M, Morita R, Komai K, Noguchi Y, Ooboshi H, Koshida R, Takahashi S, Kodama T,
Yoshimura A. Maf b prevents excess inflammation after ischemic stroke by accelerating clearance of
danger signal through MRS1. Nat Med. 2017 in press.
2) Hamada M, Nakamura M, Tran MT, Moriguchi T, Hong C, Ohsumi T, Dinh TT, Kusakabe M, Hattori
M, Katsumata T, Arai S, Nakashima K, Kudo T, Kuroda E, Wu CH, Kao PH, Sakai M, Shimano
H, Miyazaki T, Tontonz P, Takahashi S. Maf B promotes atherosclerosis by inhibiting foam-cell
apoptosis. Nat Commun. 5, 3147, 2014.
3) Morito N, Yoh K, Ojima M, Okamura M, Nakamura M, Hamada M, Yamagata K, Takahashi S.
Maf b plays a protective role in diabetic nephropathy through slit-diaphragm proteins, anti-oxidative
enzymes and Notch pathways of podocytes. J Am Soc Nephrol. 25, 2546-2557, 2014.
4) Kudo T, Sato T, Hagiwara K, Kozuma Y, Yamagami T, Ikehara Y, Hamada M, Matsumoto K, Ema M,
Murata S, Ohkohchi N, Narimatsu H, Takahashi S. C1galt1-deficient mice exhibit thrombocytopenia
due to abnormal terminal differentiation of megakaryocytes. Blood. 122, 1649-1657, 2013.
5) Takase H, Yamadera R, MatsumotoK, Kubota Y, OhtsuA, Suzuki R, KojimaT, Mochizuki H, Ishitobi
H, Takano S, Uchida K, Takahashi S, Ema M. Genome-wide identification of vascular endothelialspecific genes during development in the mouse. Blood. 120, 914-923, 2012.
6) Kusakabe M, Hasegawa K, Hamada M, Nakamura M, Ohsumi T, Suzuki H, Kudo T, Uchida K,
Ninomiya H, Chiba S, Takahashi S. c-Maf is indispensable for the microenvironment of definitive
erythropoiesis as it forms erythroblastic islands in fetal liver. Blood. 118, 1374-1385, 2011.
7) Nishikawa K, Nakashima T, Takeda S, Isogai M, Hamada M, Kimura A, Kodama T, Yamaguchi A,
Owen MJ, Takahashi S, Takayanagi H. Maf mediates the age-related switch in mesenchymal celldifferentiation. J Clin Invest. 120, 3455-3465, 2010.

6

Principal Investigator
E-mail address
URL

Sugiyama. F

Laboratory Animal Science
Fumihiro Sugiyama

bunbun@md.tsukuba.ac.jp

http://www.md.tsukuba.ac.jp/basic-med/yagami/

Other Faculty Members
Assistant Professor Seiya Mizuno: konezumi@md.tsukuba.ac.jp

Major Scientific Interests of the Group
Comparative analyses of mouse and human genomes have strongly guided the importance of thepathology of mutant mice for understanding the mechanism of human diseases.   Our main task are
the development and characterization of new gene-modified mouse models for human diseases.
Furthermore, we investigate a new strategy for genome modification in the mouse and develop a novel
mouse resource with the genome editing.
Projects for Graduate Students in Doctoral or Master’s Programs
1) Development of mouse models for human diseases2) Development of genome modification technology for mutant mouse production3) Development of mouse resources such as Cre-driver and Cre-reporter mice
Training Programs for Short Stay Students (one week – one trimester)1) Manipulation of mouse embryos
2) Genome manipulation including CRISPR/Cas9
3) Manipulation of mouse embryonic stem cells
Recent Publications
1) Hasegawa Y, Hoshino Y, Abdelaziz E. Ibrahim, Kato K, Daitoku Y, Tanimoto Y, Ikeda Y, Oishi H,
Takahashi S, Yoshiki A, Yagami K, Iseki H, Mizuno S, Sugiyama F, Generation of CRISPR/Cas9mediated bicistronic knock-in Ins1-cre driver mice.  Exp Anim. 65:319-327, 20162) Al-Soudy AS, Nakanishi T, Mizuno S, Hasegawa Y, Shawki HH, Katoh MC, Basha WA, Ibrahim
AE, El-Shemy HA, Iseki H, Yoshiki A, Hiromori Y, Nagase H, Takahashi S, Oishi H, Sugiyama F.
Germline recombination in a novel Cre transgenic line, Prl3b1-cre mouse.  Genesis. 2016 54:389-397,
2016.
3) Mizuno S, Takami K, Daitoku Y, Tanimoto Y, Dinh TT, Mizuno-Iijima S, Hasegawa Y, Takahashi
S, Sugiyama F (corresponding author), Yagami K.   Peri-implantation lethality in mice carrying
megabase-scale deletion on 5qc3.3 is caused by Exoc1 null mutation.  Sci Rep. 5:13632, 20154) Mizuno S, Tra DT, Kato K, Iijima S, Tanimoto Y, Daitoku Y, Hoshino Y, Ikawa M, Takahashi S,
Sugiyama F (corresponding author), and Yagami K.  Simple generation of albino C57BL/6J mice with
G291T mutation in the tyrosinase gene by the CRISPR/Cas9 system.  Mamm Genome. 327-334, 2014
5) Mizuno S, Tra DT, Mizobuchi A, Iseki H, Iijima S, Kim JD, Ishida J, Matsuda Y, Kunita S, Fukamizu
A, Sugiyama F (corresponding author), Yagami K.  Truncated Cales1 causes agenesis of the corpus
callosum in mice.  Lab Invest. 94:321-330, 20147

Kato. M

Experimental Pathology
Principal Investigator Mitsuyasu Kato
E-mail address mitkato@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/eatho
Other Faculty Members
Associate Professor Hiroyuki Suzuki: h-suzuki@md.tsukuba.ac.jp
Assistant Professor Yukihide Watanabe: y-watanabe@md.tsukuba.ac.jp

Major Scientific Interests of the GroupThe dynamics and molecular mechanisms how cancer cells grow in our body. The roles oftransforming growth factor-β-related molecules in cancer stem cells and cancer progression, and thedevelopment of cancer stem cell targeting therapy using non-standard macrocyclic peptides.
Projects for Regular Students in Doctoral or Master’s Programs
1) Molecular mechanisms of TGF-β-related molecules (TMEPAI, MAF K, GPNMB etc.) in cancer stem
cells and carcer progression.
2) Molecular mechanisms of a TGF-β related molecule (TSC22D4/THG-1) in squamous cell carcinoma
formation3) Establishment of cancer stem cell targeting therapy using non-standard macrocyclic peptides
Study Programs for Short Stay Students (one week ~ one trimester)1) Pathological tissue preparation, Immunohistochemistry and 3D reconstruction2) In vitro tumorigenic assays (cell proliferation, sphere formation, matrigel invasion, etc.)
Recent Publications
1) Yoon JH, Sudo K, Kuroda M, Kato M, Lee IK, Han JS, Nakae S, Imamura T, Kim J, Ju JH, Kim DK,
Matsuzaki K, Weinstein M, Matsumoto I, Sumida T, Mamura M. Phosphorylation status determines
the opposing functions of Smad2/Smad3 as STAT3 cofactors in TH17 differentiation. Nat. Commun.
6: 7600, 2015.
2) Vo Nguyen TT, Watanabe Y, Shiba A, Noguchi M, Itoh S and Kato M. TMEPAI/PMEPA1 enhances
tumorigenic activities in lung cancer cells. Cancer Sci. 105: 334-341, 2014.
3) Okita Y, Kamoshida A, Suzuki H, Itoh K, Motohashi H, Igarashi K, Yamamoto M Ogami T, Koinuma
D, and Kato M. Transforming Growth Factor-β induces transcription factors Maf K and Bach1 tosuppress expression of the heme oxygenase-1 gene. J. Biol Chem, 288: 20658-20667, 2013.
4) Itoh F, Itoh S, Adachi T, Ichikawa K, Matsumura Y, Takagi T, Festing M, Watanabe T, Weinstein M,
Karlsson S, and Kato M. Smad2/Smad3 in endothelium is indispensable for vascular stability via
S1PR1 and N-cadherin expressions. Blood 119: 5320-5328, 2012.
5) Watanabe Y, Itoh S, Goto T, Ohnishi E, Inamitsu M, Itoh F, Satoh K, Wiercinska E, Yang W,
Shi L, Tanaka A, Nakano N, Mommaas AM, Shibuya H, ten Dijke P and Kato M. TMEPAI, atransmembrane TGF-β-inducible protein, sequesters Smad proteins from active participation in TGF-βsignaling. Mol. Cell 37: 123-134, 2010.
6) Nakano N, Itoh S, Watanabe Y, Maeyama K, Itoh F, and Kato M. Requirement of TCF7L2 for TGF-βdependent transcriptional activation of the TMEPAI gene. J Biol Chem. 285: 38023-38033, 2010.
7) Tanaka A, Itoh F, Takezawa T, Itoh S and Kato M. bHLH Protein E2-2 inhibits VEGFR2 expression
and blocks endothelial cell activation. Blood, 115: 4138-4147, 2010.
8) Shi L, Itoh F, Itoh S, Takahashi S, Yamamoto M and Kato M. Ephrin-A1 promotes the malignant
progression of intestinal tumors in Apcmin/+ mice. Oncogene, 27(23): 3265-3273, 20088

Noguchi. M

Diagnostic Surgical Pathology
Principal Investigator Masayuki Noguchi
E-mail address nmasayuk@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/diagpatho/
Other Faculty Members
Associate Professor: Shingo Sakashita: sakashingo@hotmail.com
Assistant Professor: Junko Kano: junkano@md.tsukuba.ac.jp
Assistant Professor: Aya Shiba: aya-shiba@md.tsukuba.ac,jp
Assistant Professor: Noriaki Sakamoto:n.sakamoto@md.tsukuba.ac.jp
Assistant Professor: Taiki Sato:  sato310ta@gmail.com

Major Scientific Interests of the Group1) Molecular pathology of multistep carcinogenesis
2) Studies of the initial genetic alterations of precancerous lesions and early carcinoma
3) Studies of the interactions between cancer cells and interstitial cells
Projects for Regular Students in Doctoral or Master’s Programs
1) Analysis for the molecular mechanisms of pulmonar y adenocarcinogenesis. Screening of thedifferentially expressed genes and proteins between early adenocarcinoma of the lung (in situ
adenocarcinoma) and early advanced tumors.
2) Produce monoclonal antibodies against fetal swine to screen for specific antibodies against humancarcinomas.
3) In vitro and in vivo studies of the molecular mechanisms of the reproduction of liver tissue.
Study Programs for Short Stay Students (one week ~ one trimester)1) Basic techniques of immunohistochemistry, in situ hybridization, and FISH
2) Basic techniques of tissue micro-dissection
Recent Publications
1) Sato T, Shiba-Ishii A, Kim Y, Dai T, Husni RE, Hong JM, Kano J, Sakashita S, Iijima T, and Noguchi
M. miR-3941: a novel microRNA that controls IGBP1 expression and is associated with malignant
progression of lung adenocarcinoma. Cancer Sci (in press)
2) Iyama S, Ono M, Kawai-Nakahra H, Husuni RE, Dai T, Shiozawa T, Sakata A, Kohrogi H, andNoguchi M. Drebrin: A new oncofetal biomarker associated with prgrosis of lung adenocarcinoma.
Lung Cancer 102:74-81, 2016.
3) Husuni RE, Shiba-Ishii A, Iyama S, Shiozawa T, Kim Y, Nakagawa T, Sato T, Kano J, Minami Y, andNoguchi M. DNMT3a expression pattern and its prognostic value in lung adenocarcinoma. Lung
Cancer 97:59-65, 2016.
4) Shiozawa T, Iyama S, Toshima S, Sakata A, Usui S, Minami Y, Sato Y, Hizawa N, and Noguchi M.
Dimethylargine dimethylaminohydrolase promotes tumor angiogenesiss in lung adenocarcinoma.
Virchows Arch 468:179-190, 20165) Shiba-Ishii A, Kim Y, Shiozawa T, Iyama S, Satomi K, Kano J, Sakashita S, Morishita Y, andNoguchi M, Statifin accelerates progression of lung adenocarcinoma at an early state. Mol Cancer
14:142-147, 20156) Shiba-Ishii A and Noguchi M. Aberrant Stratifin overexpression is regulated by tumor-associatedCpG demetylation in lung adenocarcinoma. Am J Pathol 180:1653-1662, 2012.

9

Nagata.M

Kidney and Vascular Pathology
Principal Investigator Prof. Michio Nagata
E-mail address nagatam@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/rvpatho/

Major Scientific Interests of the Group
Kidney pathology is the main issue in our group.
Current interests include podocyte pathology, pathophysiology of FSGS, systemic vasculitis (ANCArelated) and cystogenesis in polycystic kidney.
Vascular pathology in chronic kidney disease is another focus in our group.
Projects for Regular Students in Doctoral or Master’s Programs
1) Pathophysiology and molecular mechanisms of focal segmental glomerulosclerosis from the view of
podocyte and parietal cell transdifferentiation.
2) Morphologic investigation in systemic vascular changes and kidney injury.
Training Programs for Short Stay Students (one week ~ one trimester)
1) Diagnosis of human kidney biopsy samples according to the specific interest.
2) Immunohistochemistry and molecular biologic techniques using podocyte-specific transgenic
animals.
Recent Publications
1) Aita K, Yamaguchi Y, Horita S, Ohno M, Tanabe K, Fuchinoue S, Teraoka S, Toma H, Nagata M.
Thickening of the peritubular capillary basement membrane is a useful diagnostic marker of chronic
rejection in renal allografts. Am J Transplant. 2007 Apr;7(4):923-9.
2) Aita K, Etoh M, Hamada H, Yokoyama C, Takahashi A, Suzuki T, Hara M, Nagata M. Acutepodocyte loss is the possible mechanism of heavy proteinuria in preeclampsia. Nephron Clin Prac
2009;112(2):c65-70.
3) Suzuki T, Matsusaka T, Nakayama M, Asano T, Watanabe T, Ichikawa I, Nagata M. Genetic
podocyte lineage reveals progressive podocytopenia with parietal cell hyperplasia in a murine modelof focal segmental glomerulosclerosis. Am J Pathol 2009May;174(5):1675-82.
4) Sekine Y, Nishibori Y, Akimoto Y, Kudo A, Ito N, Fukuhara D, Kurayama R, Higashihara E, Babu E,
Kanai Y, Asanuma K, Nagata M, Majumdar A, Tryggvason K, Yan K. Amino acid transporter LAT3
is required for podocyte development and function.  J Am Soc Nephrol. 2009 Jul;20(7):1586-96
5) Kobayashi A, Goto Y, Nagata M, Yamaguchi Y Granular swollen epithelial cells: a histological anddiagnostic marker for mitochondrial nephropathy Am J Sur Pathol 34: 262-70, 201010

Principal Investigator Akira Shibuya, M.D., Ph.D
E-mail address ashibuya@md.tsukuba.ac.jp
URL http://immuno-tsukuba.com
Other Faculty Members

Associate Professor: Kazuko Shibuya, M.D., Ph.D  (kazukos@md.tsukuba.ac.jp)
Assistant Professor: Satoko Tahara-Hanaoka, Ph.D (tokothr@md.tsukuba.ac.jp)
Chigusa Nakahasi-Oda, M.D., Ph.D (chigusano@md.tsukuba.ac.jp)
Tsukasa Nabekura, Ph.D (nabekura.tsukasa.fe@u.tsukuba.ac.jp)
Yumi Yamashita-Kanemaru, Ph.D (yamashitay@md.tsukuba.ac.jp)
Kazumasa Kanemaru, M.D., Ph.D (k-kanemaru@md.tsukuba.ac.jp)

Shibuya. A

Immunology

Major Scientific Interests of the GroupThe molecular mechanisms of tumor immunity, autoimmunity, infectious immunity and allergy andclinical applications of our basic research findings
Projects for Regular Students in Doctoral or Master’s Programs
1) In vivo and in vitro function of the immunoreceptors DNAM-1, Fca/mR, MAIR-I, MAIR-II, andAllergin-1, all of which were identified in our laboratory, in immune responses
2) The pathophysiological roles of the immunoreceptors in tumors, autoimmune diseases, allergy andinfectious disease
Study Programs for Short Stay Students (one week ~ one trimester)1) Honda S, Sato K, Totsuka N, Fujiyama S, Fujimoto M, Miyake K, Nakahashi-Oda C, Tahara-Hanaoka
S, Shibuya K, Shibuya A. Marginal zone B cells exacerbate endotoxic shock via interleukin-6
secretion induced by Fcα/μR-coupled TLR4 signalling.  Nat Commun, 7:11498, 2016
2) Nakahashi-Oda C, Udayanga KGS, Nakamura Y, Nakazawa Y, Miki H, Iino S, Tahara-Hanaoka
S, Shibuya K, Shibuya A. Apoptotic epithelial cells control the abundance of Treg cells at barriersurfaces.  Nat Immunol, 17:441-450, 20163) Totsuka N, Kim Y, Kanemaru K, Niizuma K, Umemoto E, Nagai K, Tahara-Hanaoka S, NakahashiOda C, Honda S, Miyasaka M, Shibuya K, Shibuya A. Toll-like receptor 4 and MAIR-II/CLM4/LMIR2 immunoreceptor regulate VLA-4-mediated inf lammatory monocyte migration.   NatCommun, 5:4710, 2014
4) Kim Y, Udayanga K G S, Totsuka N, Weinberg J B, Núñez G, Shibuya A. Gut Dysbiosis Promotes
M2 Macrophage Polarization and Allergic Airway Inflammation via Fungi-Induced PGE2.  Cell Host
Microbe, 15:95–102, 2014
5) Nakahashi-Oda C, Tahara-Hanaoka S, Shoji M, Okoshi Y, Nakano-Yokomizo T, Ohkohchi N,
Yasui T, Kikutani H, Honda S, Shibuya K, Nagata S, Shibuya A. Apoptotic cells suppress mast cell
inflammatory responses via the CD300a immunoreceptor.  J Exp Med, 209:1493-1503, 20126) Hitomi K, Tahara-Hanaoka S, Someya S, Fujiki A, Tada H, Sugiyama T, Shibayama S, Shibuya K,
Shibuya A. An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediatedimmediate hypersensitivity reactions.  Nat Immunol. 11:601-607, 201011

Ohneda. O

Regenerative Medicine and Stem Cell Biology
Principal Investigator Osamu Ohneda
E-mail address oohneda@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/basic-med/remed/
Staffs:Dr. Mami Matsuo Takasaki (Assistant Professor), mamimt@md.tsukuba.ac.jp
Dr. Toshiharu Yamashita (Assistant Professor), t-yama@md.tsukuba.ac.jp

Major Scientific Interests of the Group
1) Identification and analyses of functional stem cells for cell therapy2) Hypoxic responses in stem cell development and tumor development
Projects for Regular Students in Doctoral or Master’s Programs
1) Analysis of functional stem cells (MSC and EPC) for clinical application
2) Analysis of how hypoxic inducible factors (HIFs) are involved in stem cell development
3) Analysis of how HIFs are involved in tumor development (tumor itself and tumor endothelial cell)
Summer School Course
1) The role of Hypoxia in Mesenchymal stem cell development
2) Neural Differentiation of ES cells
Recent Publications
1) Kobayashi S, Yamashita T, Ohneda K, Nagano M, Kimura K, Nakai H, Poellinger L, Ohneda
O. Hypoxia-inducible factor-3α promotes angiogenic activity of pulmonary endothelial cells byrepressing the expression of the VE-cadherin gene. Genes Cells. 2015; Jan 28. doi: 10.1111/gtc.12215.
2) Tsuboi I, Yamashita T, Nagano M, Kimura K, Salazar GT, Ohneda O. Impaired expression of HIF-2αinduces compensatory expression of HIF-1α for the recovery from anemia. J Cell Physiol. 2015; Jan 3.
doi: 10.1002/jcp.24899.
3) Zhao Y, Matsuo-Takasaki M, Tsuboi I, Kimura K, Salazar GT, Yamashita T, Ohneda O. Dualfunctions of hypoxia-inducible factor 1 alpha for the commitment of mouse embryonic stem cells
toward a neural lineage. Stem Cells Dev. 2014; 23: 2143-2155.
4) Fukuda S, Nagano M, Yamashita T, Kimura K, Tsuboi I, Salazar G, Ueno S, Kondo M, Kunath
T, Oshika T, Ohneda O. Functional endothelial progenitor cells selectively recruit neurovascular
protective monocy te-derived F4/80(+) / Ly6c(+) macrophages in a mouse model of retinaldegeneration. Stem Cells. 2013; 31: 2149-2161.
5) Tu T, Kimura K, Nagano M, Yamashita T, Ohneda K, Sugimori H, Sato F, Sakakibara Y, Hamada H,
Yoshikawa H, Son H, and Ohneda O. Identification of human placenta-derived mesenchymal stem
cells involved in re-endothelialization. J Cell Physiol. 2011; 226: 224-235.
6) Nagano M, Kimura K, Yamashita T, Ohneda K, Nozawa D, Hamada H, Yoshikawa H, Ochiai N, andOhneda O. Hypoxia responsive mesenchymal stem cells derived from human umbilical cord blood are
effective for bone repair.  Stem Cells and Dev. 2010; 19: 1195-1210.
7) Ya m a sh it a T, Ohe d a O, Sa k iya m a A , Iwat a F, Oh ne d a K , a nd Fuji i-Ku r iya m a Y. T hemicroenvironment for erythropoiesis is regulated by HIF-2alpha through VCAM-1 in endothelial
cells.  Blood. 2008; 112: 1482-1492.
8) Yamashita T, Ohneda K. Nagano M, Miyoshi C, Kaneko N, Miwa Y, Yamamoto M, Ohneda O,
and Fujii-Kuriyama Y. HIF-2alpha in endothelial cells regulates tumor neovascularization throughactivation of ephrin A1. J Biol. Chem. 2008; 283: 18926-18936.
9) Yamashita T, Ohneda O, Nagano M, Iemitsu M, Makino Y, Tanaka H, Miyauchi H, Goto K, Ohneda
K, Fujii-Kuriyama Y, Lorenz Poellinger, and Yamamoto M. Abnormal heart development and lung
remodeling in mice lacking a HIF-related bHLH-PAS protein NEPAS. Mol. Cell. Biol. 2008; 28:1285-1297.

12

Principal Investigator Hirotoshi Miyoshi
E-mail address hmiyoshi@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/bm-engng/
Other Faculty Members

Miyoshi. H

Biomedical Engineering

Assistant Professor: Keiko Ookawa, k_ookawa@md.tsukuba.ac.jp

Major Scientific Interests of the GroupThe aims of our researches are development of bioartificial organs, e.g., ex vivo expansion systemsof hematopoietic stem/progenitor cells, bioartificial livers, and bioartificial vascular grafts, from theviewpoint of tissue engineering.
Projects for Regular Students in Doctoral or Master’s Programs
1) Effects of stromal cells on expansion of hematopoietic stem/progenitor cells in the three-dimensional(3D) cocultures of hematopoietic cells and stromal cells.
2) Effects of 3D cocultures of fetal liver cells with nonparenchymal cells on the growth and functions offetal liver cells.
3) Influence of the properties of biomaterials on the functions of cultured vascular cells.
Study Programs for Short Stay Students (one week ~ one trimester)
1) Techniques required for 3D cocultures using porous polymer scaffolds.
2) Measurements of numbers and functions of 3D-cultured cells.
Recent Publications
1) Miyoshi H, Morita M, Ohshima N, and Sato C. Expansion of mouse hematopoietic progenitor cells
in three-dimensional cocultures on frozen-thawed stromal cell layers formed within porous scaffolds.
Exp Hematol 43: 115-124, 2015.
2) Miyoshi H, Ohshima N, and Sato C. Three-dimensional culture of mouse bone marrow cells on
stroma formed within a porous scaffold: inf luence of scaffold shape and cryopreservation of thestromal layer on expansion of haematopoietic progenitor cells. J Tissue Eng Regen Med 7: 32-38,
2013.
3) Miyoshi H, Murao M, Ohshima N, and Tun T. Three-dimensional culture of mouse bone marrow cells
within a porous polymer scaffold: effects of oxygen concentration and stromal layer on expansion of
haematopoietic progenitor cells. J Tissue Eng Regen Med 5: 112-118, 2011.
4) Miyoshi H, Ehashi T, Kawai H, Ohshima N, and Suzuki S. Three-dimensional perfusion cultures ofmouse and pig fetal liver cells in a packed-bed reactor: effect of medium flow rate on cell numbers andhepatic functions. J Biotechnol 148: 226-232, 2010.
5) Koyama T, Ehashi T, Ohshima N, and Miyoshi H. Efficient proliferation and maturation of fetalliver cells in three-dimensional culture by stimulation of oncostatin M, epidermal growth factor, anddimethyl sulfoxide. Tissue Eng A 15: 1099-1107, 2009.

13

Kawaguchi. A

Infection Biology
Principal Investigator Atsushi Kawaguchi
E-mail address ats-kawaguchi@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/basic-med/infectionbiology/virology/index_english.html
Other Faculty Members
Associate Professor; Mitsuru OKUWAKI
Assistant Professor; Shoko SAITO, Kohsuke KATO
(President Special Lab.; President Kyosuke NAGATA)

Major Scientific Interests of the GroupThe research aim of this group is to understand the molecular mechanism of replication andpathogenicity of animal viruses such as influenza virus and adenovirus.  The structure and function ofvirus-encoded factors and host cell-derived factors involved in the above processes are being studied
at the atomic, molecular, cellular, and body levels.   In addition, we are particularly interested inclarifying the physiological function of identified host factors such as chromatin regulators, molecularchaperones, etc. as well as their roles in infection.
Projects for Regular Students in Doctoral or Master’s Programs
1) Identification and characterization of novel factors in virus replication
2) Control of virus diseases based on the knowledge of host defense systems, or through development ofnovel anti-viral drugs
3) Regulatory mechanism for the structure and function of chromatin
Study Programs for Short Stay Students (one week ~ one trimester)1) Molecular mechanism of host factors involved in influenza virus replication
2) Action mechanism of an anti-virus drug
Selected Recent Publications
1) Asaka MN, Kawaguchi A*, Sakai Y, Mori K, Nagata K*.  Polycomb repressive complex 2 facilitates
the nuclear export of the influenza viral genome through the interaction with M1.  Sci. Rep., 2016;6:
33608.
2) Kawaguchi A*, Hirohama M, Harada Y, Osari S, Nagata K.   Inf luenza virus induces cholesterolenriched endocytic recycling compartments for budozone formation via cell cycle-independent
centrosome maturation.  PLoS Pathog., 2015; 11(11): e1005284.
3) Sugiyama K, Kawaguchi A, Okuwaki M, Nagata K*.   pp32 and APRIL are host cell-derived
regulators of influenza virus RNA synthesis form cRNA.  eLife, 2015;4.pii:e08939.
4) Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, et al..   Long Noncoding RNA
NEAT-1-Dependent SFPQ Relocation from Promoter Region to Paraspeckle Mediates IL8 Expression
upon Immune Stimuli.  Mol. Cell, 2014;53(3):393-406.
5) Kawaguchi A, Matsumoto K, Nagata K*. YB-1 functions as a porter to lead inf luenza virus
ribonucleoprotein complexes to microtubules.  J. Virol., 2012;86:11086-11095.
6) Obayashi E, Yoshida H, Kawai F, Shibayama N, Kawaguchi A, Nagata K, Tame J R H, Park S-Y*.
The structural basis for an essential subunit interaction in influenza virus RNA polymerase.  Nature,2008;454:1127-1131.

14

Principal Investigator Kazuya Morikawa
E-mail address morikawa.kazuya.ga@u.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/basic-med/ infectionbiology/microbiology/Other Faculty Members
Other Faculty Members
Associate Professor Shinji Saito: sinsaito@md.tsukuba.ac.jp
Associate Professor (National Taiwan University) Ryosuke Ohniwa: ohniwa@md.tsukuba.ac.jp

Morikawa.K

Microbiology

Major Scientific Interests of the GroupWe are studying evolutionary/adaptation strategies of Gram-positive pathogens.   Major researchinterests include the population heterogeneity, and the acquisition of antibiotics resistance.  The main
research target is the important human pathogen, Staphylococcus aureus, that inhabits in our nasal
cavity but can cause a variety of diseases.
Projects for Regular Students in Doctoral or Master’s Programs1) Natural genetic competence in gram positive pathogens
2) Population heterogeneity
3) Dynamics of cellular structures: nucleoid and membrane4) Interaction of flora and nasal epithelial cells
Study Programs for Short Stay Students (one week ~ one trimester)1) Molecular genetic and biochemical techniques in bacteria
2) Single molecule analysis using atomic force microscope
Recent Publications
1) Medrano Romero V, and Morikawa K. Listeria monocytogenes σH contributes to expression ofcompetence genes and intracellular growth. J Bacteriol 198, 1207-1217. 2016
2) Cafini F, Nguyen le TT, Higashide M, Román F, Prieto J, and Morikawa K. Horizontal Gene
Transmission of cfr gene to MRSA and Enterococcus: role of S. epidermidis as reservoir andalternative pathway for the spread of linezolid resistance. J Antimicrob Chemother 71, 587-592. 2016
3) Ushijima Y, Yoshida O, Villanueva MJ, Ohniwa RL, and Morikawa K. Nucleoid clumping isdispensable for the Dps-dependent hydrogen peroxide resistance in Staphylococcus aureus. Microbiol
162, 1822-1828. 20164) Maudsdotter L, Imai S, Ohniwa RL, Saito S, and Morikawa K. Staphylococcus aureus dry stresssurvivors have a heritable fitness advantage in subsequent dry exposure. Microb Infec 17, 456-461.
20155) Ushijima Y, Ohniwa RL, Maruyama A, Saito S, Tanaka Y, and Morikawa K. Nucleoid compaction
by MrgA Asp56Ala/Glu60Ala does not contribute to staphylococcal cell survival against oxidative stress andphagocytic killing by macrophage. FEMS Microbiol Lett 360, 144-151. 20146) Ohniwa RL, Muchaku H, Saito S, Wada C and Morikawa K. Atomic force microscopy analysis of
the role of major DNA-binding proteins in organization of the nucleoid in Escherichia coli. PLoS One
8, e72954. 20137) Ohniwa RL, Kitabayashi K, Morikawa K. Alternative cardiolipin synthase Cls1 compensates
for stalled Cls2 function in Staphylococcus aureus under conditions of acute acid stress. FEMS
Microbiol Lett 338:141-146. 2013
8) Morikawa K, Takemura A, Inose Y, Tsai M, Nguyen Thi le T, Ohta T and Msadek T. Expressionof a cryptic secondary sigma factor gene unveils natural competence for DNA transformation in
Staphylococcus aureus. PLoS Pathog 8:e1003003. 201215

Ho. K

Molecular Parasitology
Principal Investigator Kiong Ho
E-mail address kiongho@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/basic-med/kiongho/
Ho_Lab/Welcome.html

Major Scientific Interests of the GroupOur primary research interest is to understand the gene expression of eukaryotic parasites with agoal in identifying parasite-specific processes that can be exploited as targets for novel therapeuticinterventions.  We have focused on how messenger RNA acquire 5’ cap in the protozoan parasites that
responsible for malaria and sleeping sickness.   The structure and mechanism of protozoan capping
enzyme is completely different from human host, and thus, capping is an attractive target for antiprotozoal drug discovery.  We are also investigating the mechanism of RNA repair and recombination.
RNA ligase is the key enzyme that joins the broken RNAs together.   We are characterized three
separate types of RNA ligases from various species and our immediate goal is to define how theseligases recognize the breaks in the RNA and to identify what types of RNA are repaired in the cell.
Projects for Graduate Students
1) Dissecting the mechanism and biosynthesis of hypermethylated cap 4 synthesis in Trypanosome brucei.
2) Functional characterization of mRNA recapping enzyme.
3) Defining the physiological targets for RNA ligase through genome wide screening.
Selected Publications
1) Gu H, Yoshinari S, Ghosh R, Ignatochkina AV, Gollnick PD, Murakami KS and Ho CK. (2016)
Structural and Mutational Analysis of Archaeal ATP-dependent RNA ligase Identifies Amino Acid
Required for RNA Binding and Catalysis. Nucleic Acid Res. 44 (5):2337-2347
2) Smith P, Ho CK, Takagi Y, Djaballah H, and Shuman S. (2016) Nanomolar Inhibitors of Trypanosoma
brucei RNA Triphosphatase. mBio 7(1):e00058-16. doi:10.1128/mBio.00058-16.
3) Ignatochkina AV, Takagi Y, Liu Y, Nagata K, and Ho CK. (2015) The messenger RNA decapping andrecapping pathway in Trypanosoma. Proc. Natl. Acad. Sci. USA 112:6967-6972.
4) Torchea C, Takagi Y and Ho CK. (2008) Archaea RNA Ligase is a Homodimeric Protein that
Catalyzes Intramolecular Ligation of Single-Stranded RNA and DNA. Nucleic Acid Res. 36:62186227.
5) Takagi Y, Sindkar S, Ekonomidis D, Hall MP and Ho CK. (2007) Trypanosoma brucei Encodes a
Bifunctional Capping Enzyme Essential for Cap 4 Formation on the Spliced Leader RNA. J. Biol.
Chem. 282:15995-16005.
6) Hall MP and Ho CK. (2006) Characterization of a Trypanosoma brucei mRNA Cap (Guanine N-7)
Methyltransferase. RNA 12:488-497.
7) Hall MP and Ho CK. (2006) Functional Characterization of a 48-kDa Trypanosoma brucei Cap 2
RNA Methyltransferase. Nucleic Acid Res. 34:5594-5602.
8) Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Shuman S,
Ho CK, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M,
and Tuschl T. (2005) Identification of the MicroRNAs of the Herpesvirus Family. Nature Method 2:
269-276.

16

Principal Investigator Tadachika Koganezawa
E-mail address t-kogane@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/basic-med/physiology/t-kogane/

Koganezawa. T

Neurophysiology

Major Scientific Interests of the GroupWe are studying mechanisms of cardiovascular and respiratory regulation by the central nervous
system. Especially, we are paying attention to the autonomic nervous system for the circulatory andrespiratory system.
Projects for Regular Students in Doctoral or Master’s Programs
Cardiovascular and respiratory regulation by the central nervous system plays cr ucial roles inhomeostasis. Disorder of this system causes serious problems in a living body. Despite this, it has
been remained that lots of unknown mechanisms in the cardiovascular and respiratory center. Now,
we are studying cardiovascular and respiratory regulation by the autonomic nervous system using
electrophysiological methods in situ and in vivo, and trying to investigate relationship between
disorder of the neurogenic regulation and cardiovascular and respiratory diseases.
Study Programs for Short Stay Students (one week ~ one trimester)
1) Recording of cardiovascular and respiratory parameters in human and rodent.
2) Physiological analysis of cardiovascular and respiratory parameters in human and rodent.
Recent Publications
1) Koganezawa T, Paton JFR Intrinsic chemosensitivity of rostral ventrolateral medullary sympathetic
premotor neurons in the in situ arterially perfused preparation of rats. Exp Physiol. 99(11), 1453-66 (2014)
2) Sabino-Silva R, Ceroni A, Koganezawa T, Michelini LC, Machado UF, Antunes VR Baroreceptormediated activation of sympathetic nerve activity to salivary glands. Physiol Behav, 107(3), 390-396(2012)
3) Koganezawa T, Okada Y, Terui N, Paton JF, Oku Y A μ-opioid receptor agonist DAMGO induces
rapid breathing in the arterially perfused in situ preparation of rat. Respir Physiol Neurobiol, 177(2),207-211 (2011)4) Koganezawa T, Shimomura Y, Terui N. The viscerosympathetic response in rabbits is mediatedby GABAergic and glutamatergic inputs into the sympathetic premotor neurons of the rostral
ventrolateral medulla. Exp Physiol, 95(11), 1061-1070 (2010)
5) Wang R, Koganezawa T, Terui N. Different responses of sympathetic premotor neurons in the rostral
ventrolateral medulla to stimulation of the dorsomedial hypothalamus in rabbits. Brain Res, 1356, 4453 (2010)
6) Nishimaru H, Koganezawa T, Kakizaki M, Ebihara T, Yanagawa Y. Inhibitory synaptic modulationof Renshaw cell activity in the lumbar spinal cord of neonatal mice. J Neurophysiol, 103(6), 34373447. (2010)
7) Koganezawa T, Shimomura Y, Teuri N. The role of the RVLM neurons in the viscero-sympathetic
reflex: A mini review. Auton Neurosci, 142(1-2), 17-19. (2008)8) Koganezawa T, Terui N. Differential responsiveness of RVLM sympathetic premotor neurons tohypoxia in the rabbit. Am J Physiol Heart Circ Physiol., 292, H408-414 (2007)17

Matsumoto. M

Cognitive and Behavioral Neuroscience
Principal Investigator Masayuki Matsumoto
E-mail address mmatsumoto@md.tsukuba.ac.jp
URL ttp://www.md.tsukuba.ac.jp/basic-med/cog-neurosci/
Other Faculty Members
Assistant Professor Hiroshi Yamada: h-yamada@md.tsukuba.ac.jp

Major Scientific Interests of the GroupThe goal of our research is to understand neural mechanisms underlying cognition such as attention,
memory, prediction, learning and decision making. In particular, we are investigating the role ofmonoamine systems, such as dopamine and serotonin, in cognitive functions. Experiments in ourlaboratory center on the brain of awake behaving monkeys as a model for similar systems in thehuman brain. Using electrophysiological and pharmacological techniques, we examine what signals
monoamine neurons convey while monkeys are performing cognitive tasks and how the signals,
released monoamine, work in targeted brain areas to achieve the tasks. These studies will provide
more mechanistic accounts of cognitive disorders.
Projects for Graduate Students in Doctoral or Master’s Programs1) Electrophysiological studies on roles of monoamine systems in cognitive functions
2) Pharmacological studies on roles of monoamine systems in cognitive functions3) Optogenetical manipulations of monoamine systems in awake monkeys
Training Programs for Short Stay Students (one week – one trimester)1) Analysis of cognitive performance in monkeys
2) Recording of neuron activity in awake monkeys
Recent Publications
1) Matsumoto M, Takada M, Distinct representations of cognitive and motivational signals in midbrain
dopamine neurons. Neuron, Vol.79, 1011-24, 2013
2. Matsumoto M, Hikosaka O, Electrical stimulation of the primate lateral habenula suppresses saccadic
eye movement through a learning mechanism. PLoS ONE, Vol.6, e26701, 2011
3. Matsumoto M, Hikosaka O, Two types of dopamine neuron distinctly convey positive and negative
motivational signals. Nature, Vol.459, 837-41, 2009
4. Matsumoto M, Hikosaka O, Representation of negative motivational value in the primate lateralhabenula. Nature Neuroscience, Vol.12, 77-84, 2009
5. Matsumoto M, Hikosaka O, Lateral habenula as a source of negative reward signals in dopamine
neurons. Nature, Vol.447, 1111-5, 200718

Principal Investigator Koji Tsuboi
E-mail address tsuboi-k@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/basic-med/radiation/
Other Faculty Members

Tsuboi. K

Radiation Biology

Assistant Professor Takashi Moritake: moritake@pmrc.tsukuba.ac.jp

Major Scientific Interests of the Group
Radiation biology is a field of medical sciences dealing with research on the biological actions ofionizing radiation on life or living things. In this field, it is essential to establish robust methods toevaluate and measure biological phenomena by physical parameters. The mission of this group is toclarify the biological characteristics of x-rays and proton beams and to improve the safety and efficacyof x-rays and proton beam radiotherapy.
Projects for Regular Students in Doctoral or Master’s Programs
1) Particle beam induced DNA damage and repair,2) Radiation induced tumor immunological reactions,3) Biological effects of x-ray micro beams,
Study Programs for Short Stay Students (2 weeks – 6 months)
1) Cell culture techniques and basic in vitro radio sensitivity assays
2) Methods to evaluate DNA damage in cells and tissues3) Studies on physical parameters to evaluate biological effects
Recent Publications
1) Abei M, Okumura T, Fukuda K, Hashimoto T, Araki M, Ishige K, Hyodo I, Kanemoto A, Numajiri H,
Mizumoto M, Sakae T, Sakurai H, Zenkoh J, Ariungerel G, Sogo Y, Ito A, Ohno T, Tsuboi K. A phaseI study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locallyadvanced recurrent hepatocellular carcinoma. Radiat Oncol. 2013 Oct 16;8(1):239.
2) Suzuki K, Gerelchuluun A, Hong Z, Sun L, Zenkoh J, Moritake T, Tsuboi K. Celecoxib enhances
radiosensitivity of hypoxic glioblastoma cells through endoplasmic reticulum stress. Neuro Oncol.
2013 Sep;15(9):1186-99.
3) Sun L, Moritake T, Zheng YW, Suzuki K, Gerelchuluun A, Hong Z, Zenkoh J, Taniguchi H, Tsuboi K:
In vitro stemness characterization of radioresistant clones isolated from a medulloblastoma cell line
ONS-76. J Radiat Res. 2013 Jan;54(1):61-9.
4) Hong Z, Kase Y, Moritake T, Gerelchuluun A, Sun L, Suzuki K, Terunuma T, Yasuoka K, Kumada H,
Anzai K, Sakurai H, Sakae T, Tsuboi K: Lineal energy-based evaluation of oxidative DNA damage
induced by proton beams and X-rays. Int J Radiat Biol. 2013 Jan;89(1):36-43.
5) Gerelchuluun A, Hong Z, Sun L, Suzuki K, Terunuma T, Yasuoka K, Sakae T, Moritake T, Tsuboi K.
Induction of in situ DNA double-strand breaks and apoptosis by 200 MeV protons and 10 MV X-rays
in human tumour cell lines. Int J Radiat Biol. 2011 Jan;87(1):57-70.

19

Yanagisawa. H

Vascular Matrix Biology
Principal Investigator Hiromi Yanagisawa
E-mail address hkyanagisawa@tara.tsukuba.ac.jp
URL http://saggymouse.tara.tsukuba.ac.jp/en/
Other Faculty Members
Assistant Professor: Yoshito Yamashiro: yamayoshito@tara.tsukuba.ac.jp
Assistant Professor: Aiko Sada: aisada@tara.tsukuba.ac.jp

Major Scientific Interests of the GroupThe maintenance of a proper extracellular environment comprised of extracellular matrices(ECM), ECM degrading enzymes, cytokines/growth factors, and physical factors, is crucial fornormal development and stem cell functions. The long-term goal of our research is to investigate
the interactions between extracellular environment and various cell types and elucidate how they
modulate intracellular signaling, cellular functions, and cell fate.  In particular, we focus on the vessel
wall and ECM.  We aim to identify novel ECM proteins and characterize their biochemical properties,
as well as to investigate pathophysiological functions by taking cellular, molecular biological, andgenetic engineering approaches.
Projects for Regular Students in Doctoral or Master’s Programs• Molecular mechanism of aortic aneurysm formation• Characterization of transcriptional cascade in smooth muscle cells induced by increased stiffness andmechanical stress• Novel ECM and renal calcification• Identification of novel niche for epidermal stem cells  
Training Programs for Short Stay Students (one week ~ one trimester)• Genetic and phenotypic identification of mutant mice with defective ECM• Preparation of histological sections and expression analysis by immunostaining
Recent Publications
1) Y. Yamashiro, C. L. Papke, J. Kim, L-J. Ringuette, Q-J. Zhang, Z-P. Liu, H. Mirzaei, J. E. Wagenseil,
E. C. Davis and H. Yanagisawa: Abnormal mechanosensing and cofilin activation promote theprogression of ascending aortic aneurysms in mice. Science Sig. 8(399):ra105 (2015).  
2) C. L. Papke and H. Yanagisawa: Fibulin-4 and fibulin-5 in elastogenesis and beyond: insights frommouse and human studies.  Invited mini review to Matrix Biology. 37:142-9. (2014).
3) J. Huang, Y. Yamashiro*, C. L. Papke*, Y. Ikeda*, Y. Lin, M. Patel, T. Inagami, V. P. Le, J. E.
Wagenseil and H. Yanagisawa: Angiotensin converting enzyme-induced activation of local
angiotensin signaling is required for ascending aortic aneurysms in fibulin-4 deficient mice. Science
Transl. Med. 5, 183ra58 (2013).
4) M. Budatha, S. Roshanravan, Q. Zheng, C. Weislander, S. L. Chapman, E. C. Davis, B.C. Starcher,
R. A. Word* and H. Yanagisawa*: Extracelular matrix proteases contribute to progression of pelvic
organ prolapse in mice and humans. J Clin Invest. 121(5):2048-59 (2011). (Featured in Commentaries
in JCI, Featured in “Clinical Implication of Basic Research” in N. Eng. J. Med.)
5) J. Huang, E. C. Davis, S. L. Chapman, L. Y. Budatha, M., Marmorstein, R. A. Word and H.
Yanagisawa: Fibulin-4 deficiency results in ascending aortic aneurysms: a potential link between
abnormal smooth muscle cell phenotype and aneurysm progression. Circ Res. 106(3):583-592 (2010).

20

Principal Investigator Naoyuki Tsuchiya
E-mail address tsuchiya@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/community-med/publicmd/GE/
Other Faculty Members

Tsuchiya. N

Molecular and Genetic Epidemiology

Associate Professor  Hiroshi Furukawa, furukawa-tky@umin.org
Assistant Professor  Aya Kawasaki,  a-kawasaki@md.tsukuba.ac.jp

Major Scientific Interests of the Group
Our laboratory is interested in genetic polymorphisms and their molecular mechanisms involved in
the development of human autoimmune rheumatic diseases such as systemic lupus erythematosus,
ANCA-associated vasculitis, rheumatoid arthritis and systemic sclerosis.
Projects for Regular Students in Doctoral or Master’s Programs
1) Identification of polymorphisms associated with autoimmune rheumatic diseases
2) Functional analysis of polymorphisms associated with autoimmune rheumatic diseases
Study Programs for Short Stay Students (one week ~ one trimester)
Genome database (tutorial), SNP typing (laboratory).
Recent Publications
1) Hachiya Y, Kawasaki A, Oka S, Kondo Y, Ito S, Matsumoto, Kusaoi M, Amano H, Suda A,
Setoguchi K, Nagai T, Shimada K, Sugii S, Okamoto A, Chiba N, Suematsu E, Ohno S, Katayama
M, Kono H, Hirohata S, Takasaki Y, Hashimoto H, Sumida T, Nagaoka S, Tohma S, Furukawa
H, Tsuchiya N. Association of HLA-G 3’ untranslated region polymorphisms with systemic
lupus erythematosus in a Japanese population: a case-control association study.   PLoS ONE
2016;11:e0158065.
2) Kawasaki A, Hasebe N, Hidaka M, Hirano F, Sada K-e, Kobayashi S, Yamada H, Furukawa H,
Yamagta K, Sumida T, Miyasaka N, Tohma S, Ozaki S, Matsuo S, Hashimoto H, Makino H, Arimura
Y, Harigai M, Tsuchiya N. Protective role of HLA-DRB1*13:02 against microscopic polyangiitis
and MPO-ANCA positive vasculitides in a Japanese population: a case-control study.   PLoS ONE
2016;11:e0154393.
3) Furukawa H, Oka S, Kawasaki A, Shimada K, Sugii S, Matsushita T, Hashimoto A, Komiya A,
Fukui N, Kobayashi K, Osada A, Ihata A, Kondo Y, Nagai T, Setoguchi K, Okamoto A, Okamoto A,
Chiba N, Suematsu E, Kono H, Katayama M, Hirohata S, Sumida T, Migita K, Hasegawa M, Fujimoto
M, Sato S, Nagaoka S, Takehara K, Tohma S, Tsuchiya N. Human leukocyte antigen and systemicsclerosis in Japanese: The sign of the four independent protective alleles, DRB1*13:02, DRB1*14:06,
DQB1*03:01, and DPB1*02:01.  PLoS ONE 2016;11:e0154255.
4) Gazal S, Sacre K, Allanore Y, Teruel M, Goodall AH (The CARDIOGENICS consortium), Tohma S,
Alfredsson L, Okada Y, Xie G, Constantin A, Balsa A, Kawasaki A, NIicaise P, Amos C, RodriguezRodriguez L, Chioccia G, Boileau C, Zhang J, Vittecoq O, Barnetche T, Gonzalez-Gay MA,
Furukawa H, Cantagrel A, Le Loet X, Sumida T, Hurtado-Nedelec M, Richez C, Chollet-Martin S,
Schaeverbeke T, Combe B, Khoriaty L, Coustet B, El-Benna J, Siminovitch K, Plenge R, Padyukov L,
Martin J, Tsuchiya N, Dieude P. Identification of secreted phosphoprotein 1 gene as a new rheumatoid
arthritis susceptibility gene.  Ann Rheum Dis 2015;74:e19.
5) Kawasaki A, Furukawa H, Nishida N, Warabi E, Kondo Y, Ito S, Matsumoto I, Kusaoi M, Amano
H, Suda A, Nagaoka S, Setoguchi K, Nagai T, Hirohata S, Shimada K, Sugii S, Okamoto A, Chiba N,
Suematsu E, Tokunaga K, Takasaki Y, Hashimoto H, Sumida T, Tohma S, Tsuchiya N. Associationof functional polymorphisms in Interferon Regulatory Factor 2 (IRF2) with susceptibility to systemic
lupus erythematosus: A case-control association study.  PLoS ONE 2014;9: e109764.
6) Furukawa H, Oka S, Shimada K, RA-ILD Study Consortium, Tsuchiya N, Tohma S. HLA-A*31:01
and methotrexate-induced interstitial lung disease in Japanese rheumatoid arthritis patients: a multidrug hypersensitivity marker?  Ann Rheum Dis 2013;72:153-155.

21

Yamagishi. K

Public Health Medicine
Principal Investigator Kazumasa Yamagishi
E-mail address yamagishi.kazumas.ge@u.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/community-med/publicmd/index.html

Major Scientific Interests of the Group
Epidemiology and prevention of lifestyle-related diseases in communities
Recent Publications
1) Yamagishi K, Ikeda A, Chei CL, Noda H, Umesawa M, Cui R, Muraki I, Ohira T, Imano H, Sankai T,
Okada T, Tanigawa T, Kitamura A, Kiyama M, Iso H; for the CIRCS Investigators. Serum α-linolenicand other ω-3 fatty acids, and risk of disabling dementia: community-based nested case control study.
Clin Nutr in press
2) Sairenchi T, Iso H, Yamagishi K, Irie F, Nagao M, Umesawa M, Haruyama Y, Kobashi G, Watanabe
H, Ota H. Impact and burden of each obesity-related cardiovascular risk factor in combination
with abdominal obesity on total health expenditures in adult Japanese National Health Insurance
beneficiaries: the Ibaraki Prefectural Health Study. J Epidemiol in press.
3) Saito I, Yamagishi K, Kokubo Y, Yatsuya H, Iso H, Sawada N, Inoue M, Tsugane S. Association
between mortality and incidence rates of coronary heart disease and stroke: The Japan Public HealthCenter-based Prospective (JPHC) Study. Int J Cardiol 2016; 222:281-286.
4) Sata M, Yamagishi K, Sairenchi T, Ikeda A, Irie F, Watanabe H, Iso H, Ota H. Impact of caregiver
type for 3-year-old children on subsequent between-meal eating habits and being overweight fromchildhood to adulthood: A 20-year follow-up of the Ibaraki Children’s Cohort (IBACHIL) Study.
    J Epidemiol 2015; 25:600-607

22

Principal Investigator Yoshito Kumagai
E-mail address yk-em-tu@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/community-med/environmental_
medicine/main/toppage.html
Other Faculty Members

Kumagai. Y

Environmental Medicine

Assistant Professor Yasuhiro Shinkai: ya_shinkai@md.tsukuba.ac.jp

Major Scientific Interests of the Group
This laboratory addresses the mechanisms by which environmental chemicals causing oxidative stressand covalent modification to cellular proteins affect living systems by interacting with sensor proteins
with reactive thiols (thiolate ions).  The observations obtained by this group regarding environmental
electrophiles have lent new insight into mechanisms of redox-dependent cellular signal transduction
pathways that are negatively regulated by reactive sulfur species (e.g., hydrogen sulfide anions,persulfide and polysulfide).
Projects for Regular Students in Doctoral or Master’s Programs
1) Activation of electrophilic signal transduction pathways associated with cell survival, cell proliferationand cell damage during exposure to environmental electrophiles.
2) Search for such cellular systems regulating sensor proteins covalently modified by the environmental
electrophiles.
Study Programs for Short Stay Students (one week ~ one trimester)1) Detection of cellular proteins modified by environmental electrophiles by Western blot analysis withspecific antibodies against the electrophiles.
2) Proteomics analysis by using 2D-SDS/PAGE and MALDI-TOF/MS.
Recent Publications
1) Unoki T, Abiko Y, Toyama T, Uehara T, Tsuboi K, Nishida M, Kaji T, Kumagai Y. Methylmercury,an environmental electrophile capable of activation and disruption of the Akt/CREB/Bcl-2 signaltransduction pathway in SH-SY5Y cells. Sci Rep 6: 28944, 2016.
2) Ida T, Sawa T, Ihara H, Tsuchiya Y, Watanabe Y, Kumagai Y, Suematsu M, Motohashi H, Fujii S,   
Matsunaga T, Yamamoto M, Ono K, Devarie-Baez NO, Xian M, Fukuto JM, Akaike T. Reactive
cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling. Proc Natl
Acad Sci USA 111: 7606-7611, 2014.
3) Nishida M, Sawa T, Kitajima N, Ono K, Inoue H, Ihara H, Motohashi H, Yamamoto M, Suematsu
M, Kurose H, Van der Vliet A, Freeman BA, Shibata T, Uchida K, Kumagai Y, Akaike T. Hydrogensulfide anion regulates redox signaling via electrophile sulf hydration. Nature Chem Biol 8: 714-724,
2012.
4) Toyama T, Shinkai Y, Yasutake A, Uchida K, Yamamoto M, Kumagai Y. Isothiocyanates reduce
mercury accumulation via an Nrf2-dependent mechanism during exposure of mice to methylmercury.
Environ Health Perspect 119: 1117-1121, 2011.
5) Iwamoto N, Sumi D, Ishii T, Uchida K, Cho AK, Froines JR, Kumagai Y. Chemical knockdownof protein tyrosine phosphatase 1B by 1,2-naphthoquinone through covalent modification causes
persistent transactivation of epidermal growth factor receptor. J Biol Chem 282: 33396-33404, 2007.

23

Matsuzaki. I

Occupational Psychiatry / Space Medicine #1#2
Longevity medicine Endowed Chair#1
Principal Investigator Prof. Ichiyo Matsuzaki
E-mail address ZAW00312@nifty.com
URL http://www.md.tsukuba.ac.jp/community-med/envhlth/
Other Faculty Members

Assistant Professor:Shin-ichiro Sasahara #1, #2,s-sshara@md.tsukuba.ac.jp
Assistant Professor:Satoshi Yoshino #1, satoshi-yoshino.gm@u.tsukuba.ac.jp

Major Scientific Interests of the Group
Environmental and occupational prevention of work-related diseases.
Empirical and epidemiological study on risk factors for work-related diseases and prevention.
Projects for Regular Students in Doctoral or Master’s Programs
1) Various mental disorder patients' treatment in occupational health.
Training of psychiatric clinical ability demanded on site of industrial medicine.
2) Techniques for managing working people’s mental/physical health (industrial physicians).
3) Research by use of epidemiological techniques.
Training Programs for Short Stay Students (one week ~ one trimester)
1) Health care for workers focusing on their mental health2) Clinical psychiatry (major depressive disorder, adjustment disorder etc.)
3) Return-to-work support
Recent Publications
1) I.Matsuzaki, T. Sagara, Y. Ohshita, H. Nagase, K. Ogino, A. Eboshida, S. Sasahara, H. Nakamura：
Psychological factors including sense of coherence and some lifestyles are related to General Health
Questionnaire-12 (GHQ-12) in elderly workers in Japan. Environ. Health Prev. Med., Vol.12, 71-77,
20072) S. Yoshino, S. Sasahara, T. Maeno, K. Kitaoka-Higashiguchi, Y. Tomotsune, K. Taniguchi, E.
Tomita, K. Usami , T. Haoka, H. Nakamura, I. Matsuzaki：Relationship between mental health ofJapanese residents and the quality of medical service. Journal of Physical Fitness, Nutrition and
Immunology, Vol. 17(1), 3-11, 2007
3) H. Tatsukawa, S. Sasahara, S. Yoshino, Y Tomotsune, K Taniguchi, H. Nakamura, I. Matsuzaki：
Influence of the stress coping ability of supervisors on the stress situation of their subordinates. Journalof Physical Fitness, Nutrition and Immunology, Vol.15(2), 82-87, 2005
4) Sasahara S，Matsuzaki I，Nakamura H, Ozasa K, Endo T, Imai T, Honda Y, Hatta K, Ide T,
Motohashi Y, Eboshida A：Environmental factors and lifestyles as risk factors for Japanese cedar
pollinosis in recent urban areas. Arch Complex Environ Studies Arch. Com. Eff. Study, 15,2025,2003

24

Principal Investigator Makoto Kobayashi
E-mail address makobayash@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/MDBiology/mdbiol.index.html

Kobayashi. M

Molecular and Developmental Biology

Major Scientific Interests of the Group1) Gene regulation in the cellular defense mechanisms against a variety of stresses
2) Gene regulation in the cell-fate determination especially in hematopoiesis
Projects for Graduate Students in Doctoral or Master’s Programs
1) Stress sensors in the Keap1-Nrf2 system
2) Gene regulation of Nrf2-dependent cytoprotective genes
3) Determination of hematopoietic and endothelial cell fate4) Determination of erythropoietic and myelopoietic cell fate  
5) Relationship between cell differentiation and energy pathways
Training Programs for Short Stay Students (one week – one trimester)
1) Gene expression analyses using zebrafish embryos by whole-mount in situ hybridization
2) Examination of toxicity/medicinal effects of oxidants and/or anti-oxidants using zebrafish embryos
Recent Publications
1) Nguyen TV, Fuse Y, Tamaoki J, Akiyama S, Muratani M, Tamaru Y, Kobayashi M. Conservationof the Nrf2-mediated gene regulation of proteasome subunits and glucose metabolism in zebrafish.  
Oxid Med Cell Longev, 2016:5720574,2016
2) Fuse Y, Nguyen VT, Kobayashi M. Nrf2-dependent protection against acute sodium arsenite toxicity
in zebrafish.  Toxicol Appl Pharmacol, 305:136-142,2016
3) Takeuchi M, Fuse Y, Watanabe M, Andrea CS, Takeuchi M, Nakajima H, Ohashi K, Kaneko
H, Kobayashi-Osaki M, Yamamoto M, Kobayashi M. LSD1/KDM1A promotes hematopoietic
commitment of hemangioblasts through downregulation of Etv2.   Proc Natl Acad Sci USA, 112:13922-13927,2015
4) Fuse Y, Nakajima H, Nakajima-Takagi Y, Nakajima O, Kobayashi M. Heme-mediated inhibitionof Bach1 regulates the liver specificity and transience of the Nrf2-dependent induction of zebrafish
heme oxygenase 1.  Genes Cells, 20:590-600,20155) Mukaigasa K, Nguyen LTP, Li L, Nakajima H, Yamamoto M, Kobayashi M. Genetic evidence of anevolutionarily conserved role for Nrf2 in the protection against oxidative stress.  Mol Cell Biol, 32:4455-4461,2012
6) Nakajima H, Nakajima-Takagi Y, Tsujita T, Akiyama S, Wakasa T, Mukaigasa K, Kaneko H, Tamaru
Y, Yamamoto M, Kobayashi M. Tissue-restricted induction of Nrf2 and its target genes in zebrafish
with gene-specific variations in the induction profiles.  PLoS ONE, 6:e26884,20117) Tsujita T, Li L, Nakajima H, Iwamoto N, Nakajima-Takagi Y, Ohashi K, Kawakami K, Kumagai Y,
Freeman BA, Yamamoto M, Kobayashi M. Nitro-fatty acids and cyclopentenone prostaglandins
share strategies to activate the Keap1-Nrf2 system: a study using green fluorescent protein transgenic
zebrafish.  Genes Cells, 16:46-57,20118) Kobayashi M. Harnessing the antioxidant power with ARE-inducing compounds.   Chem Biol, 17:419-420,201025

Noguchi. E

Medical Genetics
Principal Investigator Emiko Noguchi
E-mail address enoguchi@md.tsukuba.ac.jp
URL http://tsukuba-medicalgenetics.org

Major Scientific Interests of the Group1) Genetic study of asthma/atopic dermatitis/allergic rhinitis/food allergy. Linkage and association
analyses, expression profiles from human and animal tissues2) Identification of the disease-causing gene by next generation sequencing
Projects for Regular Students in Doctoral or Master’s Programs
1) Identification of novel genomic mutations associated with asthma/atopy and development of genetic
markers and therapeutic materials for personalized medicine of allergic diseases.
2) Identification of the disease-causing mutation of genetic diseases by next generation sequencers
Study Programs for Short Stay Students (one week ~ one trimester)
1) Genetic testing, genotyping, expression analyses,
2) Bioinformatics
Recent Publications
1) Imoto Y, Tokunaga T, Matsumoto Y, Hamada Y, Ono M, Yamada T, Ito Y, Arinami T, Okano M,
Noguchi E, Fujieda S Cystatin SN Upregulation in Patients with Seasonal Allergic Rhinitis. PLoS
One 8:e67057, 2013.
2) Inoue Y, Nakagawara R, Kambara T, Tanaka K, Seki K, Enomoto H, Noguchi E, Aihara M, Ikezawa
Z Prevalence of atopic dermatitis in Japanese infants treated with moisturizer since birth and its
relation to FLG mutations. Eur J Dermatol 23:288-9, 2013.
3) Kawaku S, Sato R, Song H, Bando Y, Arinami T, Noguchi E Functional analysis of BRCA1 missense
variants of uncertain significance in Japanese breast cancer families. J Hum Genet 2013.
4) Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Sakashita M, Yamada T, Fujieda S, Tanaka
S, Doi S, Miyatake A, Enomoto T, Nishiyama C, Nakano N, Maeda K, Okumura K, Ogawa H, Ikeda
S, Noguchi E, Sakamoto T, Hizawa N, Ebe K, Saeki H, Sasaki T, Ebihara T, Amagai M, Takeuchi S,
Furue M, Nakamura Y, Tamari M Genome-wide association study identifies eight new susceptibilityloci for atopic dermatitis in the Japanese population. Nat Genet 44:1222-6, 2012.
5) Noguchi E, Sakamoto H, Hirota T, Ochiai K, Imoto Y, Sakashita M, Kurosaka F, Akasawa A,
Yoshihara S, Kanno N, Yamada Y, Shimojo N, Kohno Y, Suzuki Y, Kang MJ, Kwon JW, Hong SJ,
Inoue K, Goto Y, Yamashita F, Asada T, Hirose H, Saito I, Fujieda S, Hizawa N, Sakamoto T, Masuko
H, Nakamura Y, Nomura I, Tamari M, Arinami T, Yoshida T, Saito H, Matsumoto K GenomeWide Association Study Identifies HLA-DP as a Susceptibility Gene for Pediatric Asthma in Asian
Populations. PLoS Genet 7:e1002170, 2011.

26

Principal Investigator Katsuya Honda
E-mail address k-honda@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/community-med/legal-medicine/index.html
Other Faculty Members

Honda. K

Legal Medicine

Assistant Professor  Yukiko Sugano
Research assistant  Fujio Ishizawa

Major Scientific Interests of the Group1) Development of innovative DNA profiling
2) Pathology of the cardiac sudden death3) Development of a hypersensitive toxicological test4) Study of the social aspect of the medical history
Projects for Regular Students in Doctoral or Master’s Programs
Mitochondorial polymorphisms associated with fetal diseases in Japanese
Forensic DNA analysis using next generation sequencing
Study Programs for Short Stay Students (one week ~ one trimester)
Forensic DNA typing, LC/MS/MS and GC analysis, ICP- AES analysis, Microscopic Analysis
Recent Publications
1) K Honda. DNA analysis overturns the death sentence of a condemned criminal held in custody for 8

years.  Forensic Sci Int Genet. 2015;16:e5-e6.
2) K Honda, Muramatsu H, Hashimoto R, Iwabichi Y, Tatsuzawa C, Yano S, Sugano Y.   Themitochondrial DNA polymorphisms in chromosomal aberration detected by next generation sequence.
Forensic Sci Int Genet SS. 2015;5:e375–e377.
3) Yano S, Honda K, Kaminiwa J, Nishi T, Sugano Y. DNA extraction for short tandem repeat typing
from mixed samples using anti-human leukocyte CD45 and ABO blood group antibodies. Forensic
Sci Int Genet. 2014;10:17-22.
4) Nishi T, Kurosu A, Sugano Y, Kaminiwa J, Sekine Y, Yano S, Honda K, Application of a novel
multiplex polymerase chain reaction system for 12 X-chromosomal short tandem repeats to a Japanese
population study. Legal Med. 2013;15:43-46.
5) Honda K. The Ashikaga case of Japan—Y-STR testing used as the exculpatory evidence to free aconvicted felon after 17.5 years in prison. Forensic Sci Int Genet. 2012;6:e1-e2.
6) Sugano Y, Honda K. The Succession of the Hippocratic Corpus in Modern Greece. J Japan Societyof Med History. 2010;56:67-76.

27

Muratani.M

Genome Biology
Principal Investigator Masafumi Muratani
E-mail address muratani@md.tsukuba.ac.jp
URL http://www.md.tsukuba.ac.jp/basic-med/genome/

Major Scientific Interests
We develop methods for genome and epigenome analysis of limited samples. Main area of applicationis characterization of clinical tissue samples from Tsukuba Human Tissue Bank. We try to link
histopathological features of human diseases to regulatory status of the genome.
Projects for Regular Students in Doctoral or Master’s Programs
1) Clinical sample analysis using chromatin immunoprecipitation combined with 2 nd generation
sequencing (ChIPseq) and RNAseq, data analysis and validation of potential disease biomarkers.
2) Genomics and epigenomics analysis of human and experimental mouse samples at single-cellresolution.
Study Programs for Short Stay Students (one week ~ one trimester)1) Access to genomics databases, integrative analysis of regulatory regions, gene expression and genetic
variations.
2) Genomics and epigenomics assays, chromatin immunoprecipitation, RNA assays and genotyping.
Selected Publications
1) Kumar V*, Rayan NA*, Muratani M*, Lim S, Elanggovan B, Lixia X, Lu T, Makhija H, Poschmann
J, Luf kin T, Ng HH, Prabhakar S. Comprehensive benchmarking reveals H2BK20 acetylation as a
distinctive signature of cell-state-specific enhancers and promoters. Genome Res. pii: gr.201038.115,
2016. (*Equal contribution)
2) Kakran M*, Muratani M*, Tng WJ, Liang H, Trushina DB, Sukhorukov GB, Ng HH, Antipina MN.
Layered polymeric capsules inhibiting the activity of RNases for intracellular delivery of messenger
RNA. J. Mater. Chem. B. Vol.3, 5842-5848, 2015. (*Equal contribution)3) Muratani M, Deng N, Ooi WF, Lin SJ, Xing M, Xu C, Qamra A, Tay ST, Malik S, Wu J, Lee MH,
Zhang S, Tan LL, Chua H, Wong WK, Ong HS, Ooi LL, Chow PK, Chan WH, Soo KC, Goh LK,
Rozen S, Teh BT, Yu Q, Ng HH, Tan P. Nanoscale chromatin profiling of gastric adenocarcinoma
reveals cancer-associated cryptic promoters and somatically acquired regulatory elements. Nat
Commun. 5:4361, 2014.
4) V. Kumar, M. Muratani, N.A. Rayan, P. Kraus, T. Luf kin, H.H. Ng, S. Prabhakar. Uniform, optimal
signal processing of mapped deep-sequencing data. Nature Biotechnology, Vol.31(7), 615-22, 20135) J.H. Ng*, V. Kumar*, M. Muratani*, P. Kraus, J.C. Yeo, L.P. Yaw, K. Xue, T. Luf kin, S. Prabhakar,
H.H. Ng: In vivo epigenomic profiling of germ cells reveals germ cell molecular signatures,
Developmental Cell, Vol.24(3), 324-33, 2013 (*Equal contribution)

28

Principal Investigator Masashi Yanagisawa, M.D., Ph.D.
E-mail address yanagisawa.masa.fu@u.tsukuba.ac.jp
URL http://wpi-iiis.tsukuba.ac.jp/
http://sleepymouse.tsukuba.ac.jp/
Other Faculty Member
Professor, Hiromasa Funato

Yanagisawa. M

Behavioral Neuroscience

Major Scientific Interests of the Group
1) Exploring genes regulating sleep/wake2) Real-time visualization and manipulation of neuronal mechanisms controlling sleep/wake3) Finding new drugs for sleep disorders
Projects for Regular Students in Doctoral or Master’s Programs
1) Large-scale, forward genetic screening of genes for sleep/wake regulation in mutagenized mice2) Screening for orexin receptor agonists
3) Analysis of sleep and wakefulness in genetically modified mice4) In vivo real-time imaging of neuronal activities in freely behaving mice
Training Programs for Short Stay Students (one week ~ one trimester)
1) EEG/EMG electrode implantation and recording in mice2) Patch clamp recording in cells and brain slices3) Imaging of nerve cell activities in brain slices
Recent Publications
1) Funato, H., Tsai, A.L., Willie, J.T., Kisanuki, Y., Williams, S.C., Sakurai, T., Yanagisawa, M.     Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity.
Cell Metab. 9:64-76, 2009.
2) Suzuki, A., Sinton, M.C., Green, W.R., Yanagisawa, M. Behavioral and biochemical dissociation ofarousal and homeostatic sleep need influenced by prior wakeful experience in mice.  Proc. Natl. Acad.
Sci. USA 110:10288-10293, 2013.
3) Ikeda, Y., Kumagai, H., Skach, A., Sato, M., Yanagisawa, M. Modulation of circadian glucocorticoid
oscillation through adrenal opioid-CXCR7 signaling alters emotional behavior.   Cell 155:1323-1336,
2013.
4) Lee, I.T., Chang, A.S., Manandhar, M., Shan, Y., Fan, J., Izumo, M., Ikeda, Y., Motoike, T., Dixon, S.,
Seinfeld, E.J., Takahashi, S.J., Yanagisawa, M. Neuromedin S-Producing Neurons Act as Essential
Pacemakers in the Suprachiasmatic Nucleus to Couple Clock Neurons and Dictate Circadian
Rhythms.  Neuron 85:1086-1102, 2015
5) Nagahara, T., Saitoh, T., Kutsumura, N., Irukayama-Tomobe, Y., Ogawa, Y., Kuroda, D., Gouda, H.,
Kumagai, H., Fujii, H., Yanagisawa, M., Nagase, H. Design and synthesis of non-peptide, selective
orexin recpeotor 2 agonists.  J. Med. Chem. 58: 7931-7937, 2015.
6) Funato, H., Miyoshi, C., Fujiyama, T., Kanda, T., Sato, M., Wang, Z., Ma, J., Nakane, S., Tomita, J.,
Ikkyu, A., Kakizaki, M., Hotta, N., Kanno, S., Komiya, H., Asano, F., Honda, T., Kim, J.S., Harano,K., Muramoto, H., Yonezawa, T., Mizuno, S., Miyazaki, S., Connor, L., Kumar, V., Miura, I., Suzuki,T., Watanabe, A., Abe, M., Sugiyama, F., Takahashi, S., Sakimura, K., Hayashi, Y., Liu, Q., Kume,
K., Wakana, S., Takahashi, J.S., Yanagisawa, M.   Forward genetic analysis of sleep in randomly
mutagenized mice.  Nature 539: 378-383, 20167) Ogawa, Y., Irukayama-Tomobe, Y., Murakoshi, N., Kiyama, M., Ishikawa, Y., Hosokawa, N.,
Tominaga, H., Uchida, S., Kimura, S., Kanuka, M., Morita, M., Hamada, M., Takahashi, S., Hayashi,Y., Yanagisawa, M.   Peripherally administered orexin improves survival of mice with endotoxin
shock.  eLife DOI: 10.7554/eLife.21055, 20168) Irukayama-Tomobe, Y., Ogawa, Y., Tominaga, H., Ishikawa, Y., Hosokawa, N., Ambai, S., Kawabe,Y., Uchida, S., Nakajima, R., Saitoh, T., Kanda, T., Vogt, K., Sakurai, T., Nagase, H., Yanagisawa, M.
A non-peptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexysymptomsin mousemodels.  Proc. Natl. Acad. Sci. USA, in press

29

Funato. H

Functional neuroanatomy
Principal Investigator Hiromasa Funato
E-mail address funato.hiromasa.km@u.tsukuba.ac.jp

Major Scientific Interests of the Group
1) Identification of novel genes that regulate sleep/wakefulness behavior using forward genetic approach.
2) Molecular mechanism underlying feeding and body weight homeostasis, anxiety and depressive
behavior
Projects for Regular Students in Doctoral or Master’s Programs
1) Functional characterization of novel sleep-regulating genes2) Combined approaches using viral vectors and gene-modif ied mice to uncover neural circuits
underlying sleep/wakefulness behavior, feeding and body weight homeostasis, and anxiety anddepressive behavior
Training Programs for Short Stay Students (one week ~ one trimester)1) Basic skills for EEG/EMG-based sleep analysis
2) Histological analysis using immunohistochemistry and in situ hybridization
3) Behavioral analysis of viral vector-injected mice.
Recent Publications
1) Hiromasa Funato*, Chika Miyoshi, Tomoyuki Fujiyama, Takeshi Kanda, Makito Sato, Zhiqiang
Wang, Jing Ma, Shin Nakane, Jun Tomita, Aya Ikkyu, Miyo Kakizaki, Noriko Hotta-Hirashima,
Satomi Kanno, Haruna Komiya, Fuyuki Asano, Takato Honda, Staci J. Kim, Kanako Harano, Hiroki
Muramoto, Toshiya Yonezawa, Seiya Mizuno, Shinichi Miyazaki, Linzi Connor, Vivek Kumar, Ikuo
Miura, Tomohiro Suzuki, Atsushi Watanabe, Manabu Abe, Fumihiro Sugiyama, Satoru Takahashi,
Kenji Sakimura, Yu Hayashi, Qinghua Liu, Kazuhiko Kume, Shigeharu Wakana, Joseph S Takahashi,
Masashi Yanagisawa*.
Forward-genetics analysis of sleep in randomly mutagenized mice
Nature, 539, 378-383, 2016 (* corresponding author)
DOI: 10.1038/nature20142
2) Mohammad Sarowar Hossain, Fuyuki Asano, Tomoyuki Fujiyama, Chika Miyoshi, Makito Sato, Aya
Ikkyu, Satomi Kanno, Noriko Hotta, Miyo Kakizaki, Takato Honda, Staci J. Kim, Haruna Komiya,
Ikuo Miura, Tomohiro Suzuki, Kimio Kobayashi, Hideki Kaneda, Vivek Kumar, Joseph S. Takahashi,
Shigeharu Wakana, Hiromasa Funato*, Masashi Yanagisawa* (*corresponding author)
Identification of mutations through dominant screening for obesity using C57BL/6 substrains
Scientific Reports 6:32453, 2016
DOI: 10.1038/srep32453
3) Kenkichi Takase, Yousuke Tsuneoka, Satoko Oda, Masaru Kuroda, Hiromasa Funato High-fat dietfeeding alters olfactory-, social- and reward-related behaviors of mice independent of obesity
Obesity (Silver Spring) 24:886-894, 2016
doi: 10.1002/oby.21441
4) Takeshi Kanda, Natsuko Tsujino, Eriko Kuramoto, Yoshimasa Koyama, Etsuo A. Susaki, Sachiko
Chikahisa, Hiromasa Funato
Sleep as a biological problem: an overview of frontiers in sleep research
Journal of Physiological Sciences 66:1-13, 2016
doi: 10.1007/s12576-015-0414-3

30

Principal Investigator Prof. Hiroshi Nagase, Ph.D.
Associate Prof. Noriki Kutsumura, Ph.D.
E-mail address nagase.hiroshi.gt@u.tsukuba.ac.jp
kutsumura.noriki.gn@u.tsukuba.ac.jp
URL http://nagase.wpi-iiis.tsukuba.ac.jp
Other Faculty Members

Assistant Prof. Naoshi Yamamoto, Ph.D.: yamamoto.naoshi.gu@u.tsukuba.ac.jp
Assistant Prof. Tsuyoshi Saitoh, Ph.D.: tsuyoshi-saito.gf@u.tsukuba.ac.jp
Assistant Prof. Yasuyuki Nagumo, Ph.D.: nagumo.yasuyuki.fu@u.tsukuba.ac.jp

Nagase. H
Kutsumura. N

Medicinal Chemistry, Organic Chemistry

Major Scientific Interests of the Group1) Design and Synthesis of Orexin Agonists2) Design and Synthesis of Opioid Receptor Agonists and Antagonists
3) Clarification of Mechanism of Drug Resistance and Dependence
Projects for Regular Students in Doctoral or Master’s Programs
1) Study of Medicinal Chemistry2) Study of Organic Chemistry3) Research Development of New Drugs
Training Programs for Short Stay Students (one week ~ one trimester)1) Organic Synthesis of Opioid Compounds
2) Organic Synthesis of Orexin Ligands
3) Purification and Separation Technique4) Basic Drug Design
Selected Recent Publications
1) Watanabe, Y.; Kitazawa, S.; Nemoto, T.; Hirayama, S.; Iwai, T.; Fujii, H.; Nagase, H., Design andsynthesis of novel opioid ligands with an azabicyclo[2.2.2]octane skeleton having a 7-amide chain andtheir pharmacologies, Bioorg. Med. Chem. 2013, 21, 3032-3050.
2) Kutsumura, N.; Matsubara, Y.; Niwa, K.; Ito, A.; Saito, T., Novel One-pot Method for Regioselective
Bromination and Sequential Carbon−Carbon Bond-forming Reactions of Allylic Alcohol Derivatives,
Eur. J. Org. Chem. 2013, 3337-3346.
3) Nemoto, T.; Yamamoto, N.; Wada, N.; Harada, Y.; Tomatsu, M.; Ishihara, M.; Hirayama, S.; Iwai,
T.; Fujii, H.; Nagase, H., The effect of 17-N substituents on the activity of the opioid κ receptor in
nalfurafine derivatives, Bioorg. Med. Chem. Lett. 2013, 23, 268-272.
4) Nagase, H.; Imaide, S.; Hirayama, S.; Nemoto, T.; Fujii, H., Essential structure of opioid κ receptor
agonist nalfurafine for binding to the κ receptor 2: Synthesis of decahydro(iminoethano) phenanthrene
derivatives and their pharmacologies, Bioorg. Med. Chem. Lett. 2012, 22, 5071-5074.
5) Nagase, H.; Akiyama, J.; Nakajima, R.; Hirayama, S.; Nemoto, T.; Gouda, H.; Hirono, S.; Fujii,
H., Synthesis of new opioid derivatives with a propellane skeleton and their pharmacology. Part 2:
Propellane derivatives with an amide side chain, Bioorg. Med. Chem. Lett. 2012, 22, 2775-2779.
6) Kutsumura, N.; Kiriseko, A.; Saito, T., Total Synthesis of (+)-Heteroplexisolide E, Heterocycles 2012,
86, 1367-1378.
7) Kutsumura, N; Kiriseko, A.; Saito, T., First total synthesis of (+)-heteroplexisolide E, Tetrahedron
Lett. 2012, 53, 3274-3276.
8) Nagase, H.; Imaide, S.; Yamada, T.; Hirayama, S.; Nemoto, T.; Yamaotsu, N.; Hirono, S.; Fujii, H.,
Essential Structure of Opioid κ Receptor Agonist Nalfurafine for Binding to κ Receptor 1: Synthesis of
Decahydroisoquinoline Derivatives and Their Pharmacologies, Chem. Pharm. Bull. 2012, 60, 945-948.

31

Liu. Q

Biochemistry and Molecular Genetics
Principal Investigator Qinghua Liu, Ph.D.
E-mail address qinghua.liu@utsouthwestern.edu
URL http://profiles.utsouthwestern.edu/profile/50723/qinghua-liu.html
Other Faculty Member:
Assistant Professor: Liqin Cao, Ph.D.; Instructor: Zhiqiang Wang, Ph.D.
Researcher: Makito Sato, Ph.D.; Researcher: Daniela Klewe-Nebenius

Major Scientific Interests of the Group
1) RNA Interference and MicroRNAs
2) Molecular Mechanism of Sleep/Wake Regulation
3) Molecular Mechanism of Innate Fear
Projects for Regular Students in Doctoral or Master’s Programs
1) We combine forward genetic screen and classical biochemical fractionation & reconstitution
approaches to identify novel factors (e.g. R2D2, C3PO, and etc.) and characterize their precise
function in the RNA Interference (RNAi) and microRNA pathways.
2) We will understand the fundamental mechanism of Sleep/Wake control by integrating mouse
genetic screen, quantitative proteome/phosphor-proteome analysis of Sleepy mutant brains, classicalbiochemistry and modern neuroscience approaches.
3) We will understand the fundamental mechanism of innate fear (of predator) and the molecularprinciples of human emotions by conducting the first forward genetic screen in mice in search of the“fearless” mutants and the core molecular pathways underlying the fear response.  
Training Programs for Short Stay Students (one week ~ one trimester)1) Molecular cloning (e.g. for constructing CRISPR knockout and knockin mice/cell lines)
2) “Fearless” screen3) Sleep (EEG/EMG) recording

Recent Publications
1) Z. Wang, S. Liu, M. Kakizaki, Y. Hirose, Y. Ishikawa, H. Funato, M. Yanagisawa, Y. Yu, Q.
Liu. Orexin/Hypocretin activates mTOR complex 1 (mTORC1) via an Erk/Akt-independent andcalciumstimulated lysosome v-ATPase pathway. J Biol Chem, 289: 31950-31959 (2014)
2) Y. Liu, H. Tan, H. Tian, C. Liang, S. Chen, Q. Liu. Autoantigen La promotes RNAi, antiviral
response, and transposon silencing by facilitating multi-turnover RISC catalysis, Molecular Cell
44:502-8 (2011).
3) X. Ye, N. Huang, Y. Liu, Z. Paroo, C. Huerta, P. Li, S. Chen, Q. Liu*, H. Zhang* (co-corresponding
authors). Structure of C3PO and mechanism of human RISC activation. Nat Struct Mol Biol. 18:650657 (2011)
4) Paroo, X. Ye, S. Chen, and Q. Liu. Phosphorylation of the human micro-RNA generating complex
mediates MAPK/Erk signaling. Cell 139:112-122 (2009)5) Y. Liu, X. Ye, F. Jiang, C. Liang, D. Chen, J. Peng, L.N. Kinch, N.V. Grishin, and Q. Liu. C3PO, an
endoribonuclease that promotes RNAi by facilitating RISC activation. Science, 325:750-753 (2009)32

Principal Investigator Masanori Sakaguchi
E-mail address masanori.sakaguchi@gmail.com
URL http://sakurai-sakaguchi.wpi-iiis.tsukuba.ac.jp/

Sakaguchi. M

Manipulation of memory during sleep

Major Scientific Interests of the GroupOur group strives to investigate the function of sleep in memory.  We have recently discovered thatfear memory can be unlearned by exposing subject to a sound which is associated with the memory (Sci.
Rep, in minor revision).  Also, we found that fear memory can be manipulated by silencing the adultborn neurons during sleep using optogenetics (in prep).  Our hope is that these findings will contributeto the development of new therapeutic strategy for memory related disorders including PTSD.   Wewelcome motivated and self-driven students and researchers anytime for lab visiting.
Projects for Regular Students in Doctoral or Master’s Programs
1) Optogenetic manipulation of memory during sleep2) Imaging neuronal activity using miniaturized end-microscope
3) Molecular mechanisms of memory processing during sleep
Training Programs for Short Stay Students (one week ~ one trimester)4) Sleep-stage specific intervention of memory5) Learning basic of optogenetics
Recent Publications (10 first/correspondent, 28 international publications)
1) Sakaguchi M and Hayashi Y, Catching the engram: strategies to examine the memory trace, Mol.
Brain 2012, 5:32(359 viewed in the first 10days, 6th best viewed during the 1st month)2) Sakaguchi M and Okano H. Neural stem cells, adult neurogenesis and galectins: from bench to
bedside, Dev. Neurobiol., 2012, 72(7):1059-67.
3) Arruda-Carvalho M*., Sakaguchi M*, Akers KG., Josselyn SA., Frankland PW., Post-training
ablation of adult-generated neurons degrades previously-acquired memories., J. Neurosci. 2011,
31(42):15113- 27., *The authors contributed equally4) Sakaguchi M, Imaizumi Y, Shingo T, Tada H, Hayama K, Yamada O, Morishita T, Kadoya T,
Uchiyama N, Shimazaki T, Kuno A, Poirier F, Hirabayashi J, Sawamoto K, Okano H., Regulationof adult neural progenitor cells by Galectin-1/beta1 Integrin interaction., J. Neurochem., 2010,
113(6):1516-24.
5) Sakaguchi M., Shingo T., Shimazaki T., Okano H.J., Shiwa M., Ishibashi S., Oguro H., Ninomiya
M., Kadoya T., Horie H., Shibuya A., Mizusawa H., Poirier F., Nakauchi H., Sawamoto K., Okano H.
A carbohydrate binding protein, Galectin-1, promotes proliferation of adult neural stem cells. PNAS,
2006, 103:pp7112-7117 (Track II direct submission)33

Lazarus. M

Systems Sleep Biology
Principal Investigator Michael Lazarus, Ph.D
E-mail address lazarus.michael.ka@u.tsukuba.ac.jp
URL http://www.wpiiiislazaruslab.org
Other Faculty Members
Researcher Yo Oishi, Ph.D.
Researcher Yoko Takata, Ph.D.

Major Scientific Interests of the Group1) Motivated behavior as a major sleep-regulating factor
2) Optopharmacology to regulate sleep3) REM sleep and the links to the desire for sugary and fatty foods (http://www.asahi.com/ajw/articles/
AJ201701160072.html)
Projects for Regular Students in Doctoral or Master’s Programs
1) Use of genetically engineered systems to dissect neural circuitry regulating sleep and wakefulness2) Development of optopharmacologic tools to control sleep3) Living in space: hypothermia as risk factor for memory consolidation (Collaborative project with
Satoshi Furukawa/ JAXA)
4) Role of brainstem neurons in linking REM sleep to the consumption of weight promoting foods
Training Programs for Short Stay Students (one week ~ one trimester)
1) EEG/EMG electrode implantation and recording in mice2) Engineering and production of adeno-associated viruses
3) Optogenetic and chemocogenetic modulation of neural circuitry by using stereotaxic microinjectionsof viral vectors
4) Immunohistochemistry and in situ hybridization of brain tissue
Recent Publications
1) McEown K, Takata Y, Cherasse Y, Nagata N, Aritake K, Lazarus M. Chemogenetic inhibition of themedial prefrontal cortex reverses the effects of REM sleep loss on sucrose consumption. eLife, 5:
e20269, 20162) Oishi Y, Suzuki Y, Takahashi K, Yonezawa T, Kanda T, Takata Y, Cherasse Y, Lazarus M. Activationof ventral tegmental area dopamine neurons produces wakefulness through dopamine D2–likereceptors in mice. Brain Struct Funct, doi: 10.1007/s00429-017-1365-73) Lazarus M, Chen J-F, Urade Y, Huang Z-L. Role of the basal ganglia in the control of sleep andwakefulness. Curr Opin Neurobiol 2013, 23: 780-785.
4) Lazarus M, Huang Z-L, Lu J, Urade Y, Chen J-F. How do the basal ganglia regulate sleep-wakebehavior? Trends Neurosci 2012, 35: 723-732.
5) Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass C, Winsky-Sommerer R, Semba
K, Fredholm B, Boison D, Hayaishi O, Urade Y, Chen JF. Arousal effect of caffeine depends on
adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci 2011, 31: 10067-10075.
6) Gautron L*, Lazarus M* (Co-first author), Scott MM, Saper CB, Elmquist JK. Identifying the efferent
projections of leptin-responsive neurons in the dorsomedial hypothalamus using a novel conditional
tracing approach. J Comp Neurol 2010, 518: 2090–2108.
7) Lazarus M, Yoshida K, Coppari R, Bass CE, Mochizuki T, Lowell BB, Saper CB. EP3 prostaglandin
receptors in the median preoptic nucleus are critical for fever responses. Nat Neurosci 10(9), 1131-3(2007).

34

Principal Investigator Yoshihiro Urade, PhD
E-mail address urade.yoshihiro.ft@u.tsukuba.ac.jp
URL
Other Faculty Members

Urade. Y

Molecular Sleep Biology

Associate Professor Kosuke Aritake, PhD
Researcher Yoan Cherasse, Ph.D.
Researcher Mahesh K. Kaushik, Ph.D.
Researcher Olga Malyshevskaya, Ph.D.
Researcher Nanae Nagata

Major Scientific Interests of the Group
1) Role of prostaglandin D2 in sleep-wake regulation
2) Role of Sox5 in controlling sleep cycle
3) Relationship between sleep and neurodegenerative diseases
Projects for Regular Students in Doctoral or Master’s Programs
1) Involvement of glutamatergic neurons in sleep regulation
2) Relationship between sleep and memory in gene-manipulated animals
3) Screening of new sleep-regulatory natural compounds
Training Programs for Short Stay Students (one week ~ one trimester)1) Basic and advanced molecular biology and biochemistry experiments2) Sleep recording and analysis
3) Mouse brain surgery and gene manipulation
4) Screening of new sleep-regulatory natural compounds
Recent Publications
1) Kaushik MK, Kaul SC, Wadhwa R, Yanagisawa M, Urade Y Triethylene glycol, an active componentof Ashwagandha (Withania somnifera) leaves, is responsible for sleep induction.  PLoS One. 2017 inpress2) Saito H, Cherasse Y, Suzuki R, Mitarai M, Ueda F, Urade Y. Zinc-rich oysters as well as zinc yeastand astaxanthin-enriched food improved sleep efficiency and sleep onset in a randomized controlled
trial of healthy individuals.  Mol Nutr Food Res. 2017 in press
3) Zhang BJ, Shao SR, Aritake K, Takeuchi A, Urade Y, Huang ZL, Lazarus M, Qu WM. Interleukin1β induces sleep independent of prostaglandin D2 in rats and mice.   Neuroscience. 6;340:258-267.
20174) Kida T, Ayabe S, Omori K, Nakamura T, Maehara T, Aritake K, Urade Y, Murata T. Prostaglandin
D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.  PLoS One. 19;11(12):e0167729. 2016
5) Nakamura Y, Midorikawa T, Monoi N, Kimura E, Murata-Matsuno A, Sano T, Oka K, Sugafuji T,
Uchiyama A, Murakoshi M, Sugiyama K, Nishino H, Urade Y. Oral administration of Japanese sakeyeast (Saccharomyces cerevisiae sake) promotes non-rapid eye movement sleep in mice via adenosine
A2A receptors.  J Sleep Res. 25(6):746-753. 2016
6) Nakamura T, Maeda S, Horiguchi K, Maehara T, Aritake K, Choi BI, Iwakura Y, Urade Y, Murata T.
PGD2 deficiency exacerbates food antigen-induced mast cell hyperplasia.  Nat Commun. 10;6:7514.
20157) Cherasse Y, Saito H, Nagata N, Aritake K, Lazarus M, Urade Y. Zinc-containing yeast extract
promotes nonrapid eye movement sleep in mice.  Mol Nutr Food Res. 59(10):2087-93. 20158) Trimarco A, Forese MG, Alfieri V, Lucente A, Brambilla P, Dina G, Pieragostino D, Sacchetta P,
Urade Y, Boizet-Bonhoure B, Martinelli Boneschi F, Quattrini A, Taveggia C. Prostaglandin D2
synthase/GPR44: a signaling axis in PNS myelination.  Nat Neurosci. 17(12):1682-92. 2014
9) Moniot B, Ujjan S, Champagne J, Hirai H, Aritake K, Nagata K, Dubois E, Nidelet S, Nakamura M,
Urade Y, Poulat F, Boizet-Bonhoure B. Prostaglandin D2 acts through the Dp2 receptor to influence
male germ cell differentiation in the foetal mouse testis.  Development. 141(18):3561-71. 2014
10)Kaushik MK, Aritake K, Kamauchi S, Hayaishi O, Huang ZL, Lazarus M, Urade Y. Prostaglandin
D2 is crucial for seizure suppression and postictal sleep, Exp. Neurol. 253:82-90. 201435

Vogt. K

Sleep Neuroscience
Principal Investigator Kaspar Vogt MD- PhD
E-mail address vogt.kaspar.fu@u.tsukuba.ac.jp
URL

Major Scientific Interests of the Group
1) Cortical networks underlying sleep rhythms
2) The neural basis of sleep homeostasis
3) In-vivo functional imaging of neural activity
Projects for Regular Students in Doctoral or Master’s Programs
1) The role of cortical neurons in the generation of sleep patterns2) Cortical circuits as regulators of sleep homeostasis3) Optogenetic control of sleep rhythms and its effects on sleep quality       Training Programs for Short Stay Students (one week ~ one trimester)1) Local field potential and EEG recordings2) Basic neurophysiology (patch-clamp and field recordings in-vitro)
3) Functional imaging of neural activity4) Generation and use of viral vectors
Recent Publications
1) Vogt K. Diversity in GABAergic signaling. Adv Pharmacol. 2015;73:203-22.
2) Willadt S, Canepari M, Yan P, Loew LM, Vogt KE. Combined optogenetics and voltage  sensitive dye
imaging at single cell resolution. Front Cell Neurosci. 2014;8:311.
3) Canepari M, Vogt KE, De Waard M, Zecevic D. Combining Ca2+ and membrane potential  imaging
in single neurons. Cold Spring Harb Protoc. 2013 Dec 1;2013(12):1161-4.
4) Willadt S, Nenniger M, Vogt KE. Hippocampal feedforward inhibition focuses excitatory synaptic
signals into distinct dendritic compartments. PLoS One. 2013;8(11):e80984.
5) Baudouin SJ, Gaudias J, Gerharz S, Hatstatt L, Zhou K, Punnakkal P, Tanaka KF,
Spooren W, Hen R, De Zeeuw CI, Vogt K, Scheiffele P. Shared synapticpathophysiology in syndromic
and nonsyndromic rodent models of autism. Science. 2012 Oct 5;338(6103):128-32.
6）Vogt KE, Gerharz S, Graham J, Canepari M. High-resolution simultaneous voltage and Ca2+ imaging.
J Physiol. 2011 Feb 1;589(Pt 3):489-94.

36

Principal Investigator Yu Hayashi, Ph.D.
E-mail address hayashi.yu.fp@u.tsukuba.ac.jp
URL http://hayashi.wpi-iiis.tsukuba.ac.jp/index.html

Hayashi.Y

Brain Maturation/Evolution

Major Scientific Interests of the Group
1) Elucidating the function of sleep2) Revealing the evolutionary origin of REM and non-REM sleep3) Developing new therapeutics for neural disorders
Projects for Regular Students in Doctoral or Master’s Programs
1) Search for the function of REM sleep using mouse genetics
2) Search for the function of sleep using C. elegans genetics
3) Comparison of sleep-regulating neuron in animals with & without REM sleep4) Development of novel therapeutics focusing on sleep-regulating neurons
Training Programs for Short Stay Students (one week ~ one trimester)1) Viral vector-mediated gene transfection in mice2) Sleep analyses in roundworms in C. elegans
Recent Publications
1) Funato H, Miyoshi C, Fujiyama T, Kanda T, Sato M, Wang Z, Ma J, Nakane S, Tomita J, Ikkyu
A, Kakizaki M, Hotta-Hirashima N, Kanno S, Komiya H, Asano F, Honda T, Kim SJ, Harano K,
Muramoto H, Yonezawa T, Mizuno S, Miyazaki S, Connor L, Kumar V, Miura I, Suzuki T, Watanabe
A, Abe M, Sugiyama F, Takahashi S, Sakimura K, Hayashi Y, Liu Q, Kume K, Wakana S, Takahashi
JS, Yanagisawa M, “Forward-genetics analysis of sleep in randomly mutagenized mice,” Nature 539,
378–383 (2016)
2) Hayashi Y, Kashiwagi M, Yasuda K, Ando R, Kanuka M, Sakai K, Itohara S, “Cells of a common
developmental origin regulate REM/non-REM sleep and wakefulness in mice,” Science 350, 957-961  
(2015)
3) Hayashi Y, *Hirotsu T (*equal contribution), *Iwata R (*equal contribution), Kage-Nakadai E,
Kunitomo H, Ishihara T, Iino Y, Kubo T, “A trophic role for Wnt-Ror kinase signaling during
developmental pruning in Caenorhabditis elegans”, Nature Neuroscience 12, 981-987 (2009)4) *Kage E (*equal contribution), *Hayashi Y (*equal contribution), Takeuchi H, Hirotsu T, Kunitomo H,
Inoue T, Arai H, Iino Y, Kubo T, “MBR-1, a novel helix-turn-helix transcription factor, is required forpruning excessive neurites in Caenorhabditis elegans”, Current Biology 15, 1554-1559 (2005)

37

Sakurai. T

Molecular Behavioral Physiology
Principal Investigator
E-mail address
URL

Takeshi Sakurai, M.D., Ph.D.

takeshi.sakuraigf@u.tsukuba.ac.jp

http://wpi-iiis.tsukuba.ac.jp/

Major Scientific Interests of the Group
1) To seek out novel factors that regulate emotion, feeding, and sleep/wakefulness states.
2) To define roles of neuropeptides in regulation of animals’ behavior.
3) To explore neural circuits that play a prominent role in regulation of animals’ behavior
Projects for Regular Students in Doctoral or Master’s Programs
1) Input and output tracings of neuron populations that play important roles in regulation of animals’
behavior
2) Optogenetic/pharmacogenetic manipulation of these circuits.
3) Comprehensive behavioral analyses of genetically-modified mice.
4) Developing new optogenetic/pharmacogenetic tools.
Training Programs for Short Stay Students (one week ~ one trimester)
1) Behavioral experiments on genetically-modified mice2) EEG/EMG electrode implantation and recording in mice3) Patch clamp recording in brain slices4) Optogenetic manipulations on behavior in mice
Recent Publications
1) Mieda, M., Ono, D., Hasegawa, E., Okamoto,H., Honma, K., Honma, S., Sakurai, T. Cellular Clocks
in AVP Neurons of the SCN Are Critical for Interneuronal Coupling Regulating Circadian Behavior
Rhythm. Neuron, 2015, 85(5): 1103–1116.
2) Sakurai T. The role of orexin in motivated behaviours.  Nat Rev Neurosci. 2014,15(11):719-31.
3) Matsuki, T., Nomiyama, M, Takahira, H., Hirashima, N., Kilduff, T.S., Kunita, S., Takahashi, S.,
Yagami, K., Bettler, B., Yanagisawa, M., Sakurai, T. Selective loss of GABAB receptors in orexin/
hypocretin-producing neurons results in disrupted sleep/wakefulness architecture.  Proc. Natl. Acad.,
Sci., USA., 106(11), 4459-64, 20094) Sakurai T. Neural Circuit of Orexin (Hypocretin):Mainaining Sleep and Wakefulness.   Nat. Rev.
Neurosci. 8, 171-181, 2007.
5) Sakurai T, et al. Input of Orexin/Hypocretin Neurons Revealed by a Genetically Encoded Tracer inMice.  Neuron 46(2):297-308,2005
6) Yamanaka A. Beuckmann CT. Willie JT. Hara J. Tsujino N. Mieda M. Tominaga M. Yagami K.
Sugiyama F. Goto K. Yanagisawa M. and Sakurai T. Hypothalamic Orexin neurons regulate arousal
according to energy balance in mice.  Neuron. 38:701-713, 2003
7) Hara J, BeuckmannCT, Nambu T, Willie JT, Chemelli RM, Sinton CM, Sugiyama F, Yanagi K, GotoK, Yanagisawa M, Sakurai T. Genetic Ablation of Orexin Neurons in Mice Results in Narcolepsy,
Hypophagia and Obesity.  Neuron 30:345-354, 2001
8) Sakurai T, et al. Orexins and orexin receptors: A family of hypothalamic neuropeptides and G proteincoupled receptors that regulate feeding behavior.  Cell 92:573-585, 1998

38

Principal Investigator
E-mail address
URL

Prof. Shunsuke Ishii

sishii@rtc.riken.jp

Ishii. S

Functional Genomics

http://rtcweb.rtc.riken.jp/lab/mg/en/mg.html

Other Faculty Member
Associate Professor  Toshie Shinagawa: sinagawa@rtc.riken.jp

Major Scientific Interests of the Group
Regulation of transcription, a process of mRNA synthesis from DNA, is a basis of biologicalphenomena.   Our group aims to solve the mechanism of transcriptional control via analyzing
transcriptional regulators, which are involved in development, immunity, and various diseases, using
whole animal body system. Recently, we are focusing on epigenetic regulation of transcription.
Projects for Regular Students in Doctoral or Master’s Programs
1) Epigenetic memory induced by environmental factors
2) Epigenetic state of totipotent cells
Training Programs for Short Stay Students (one week ~ one trimester)1) Molecular biology experiments for studying transcriptional control
2) Genetic experiments using Drosophila and mice
Recent Publications
1) Yoshida K, Maekawa T, Zhu Y, Renard-Guillet C, Chatton B, Inoue K, Uchiyama T, Ishibashi
K, Yamada T, Ohno N, Shirahige K, Okada-Hatakeyama M and Ishii S.   The transcription factor
ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate
immunological memory.  Nat. Immunol. 16, 1034-1043, 2015.
2) Shinagawa T, Huynh ML, Takagi T, Tsukamoto D, Tomaru C, Kwak HG, Dohmae N, Noguchi J and
Ishii S.   Disruption of Th2a and Th2b genes causes defects in spermatogenesis.   Development 142,
1287-1292, 2015.
3) Shinagawa T, Takagi T, Tsukamoto D, Tomaru C, Huynh LM, Sivaraman P, Kumarevel T, Inoue
K, Nakato R, Katou Y, Sado T, Takahashi S, Ogura A, Shirahige K and Ishii S.   Histone variants
enriched in oocytes enhance reprogramming to induced pluripotent stem cells.   Cell Stem Cell 14,
217-227, 2014.
4) Seong KH, Li D, Shimizu H, Nakamura R and Ishii S. Inheritance of stress-induced, ATF-2dependent epigenetic change.  Cell 145, 1049-1061, 2011.
5) Maekawa T, Kim S, Nakai D, Makino C, Takagi T, Ogura H, Yamada K, Chatton B and Ishii S.
Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor
gene.  EMBO J. 29, 196-208, 2010.

39

Nakamura. Y

Experimental Hematology
Principal Investigator
E-mail address
URL

Prof. Yukio Nakamura

yukio.nakamura@riken.jp

http://www.brc.riken.jp/lab/cell/

Major Scientific Interests of the GroupIn vitro production of red blood cells (RBCs) able to be used in the clinic.  For this purpose, we
are attempting to establish immortalized human RBC progenitor cell lines from various cellsources such as hematopoietic stem cells, ES cells and iPS cells. In addition, we are studying themechanisms of enucleation of RBC progenitor cells so as to improve the efficiency of in vitro
enucleation.
Projects for Regular Students in Doctoral or Master’s Programs

1) Cell culture of human ES and iPS cells. Induction of hematopoietic cells from human ES andiPS cells. Establishment of immortalized human hematopoietic cell lines from various cellsources such as hematopoietic stem cells, ES cells and iPS cells.
2) Molecular mechanisms of enucleation of RBC progenitor cells.
Training Programs for Short Stay Students (one week ~ one trimester)
1) Cell culture of mouse ES or iPS cells.
2) Cell analysis by flow cytometer.
Recent Publications

1) Masuda, T., Wang, X., Maeda, M., Canver, M.C., Sher, F., Funnell, A.P.W., Fisher, C., Suciu, M.,
Martyn, G.E., Norton, L.J., Zhu, R., Kurita, R., Nakamura, Y., Xu, J., Higgs, D.R., Crossley, M.,
Bauer, D.E., Orkin, S.H., Kharchenko, P., and Maeda, T. Transcription factors LRF and BCL11A
independently repress expression of fetal hemoglobin.  Science 351: 285-289 (2016)
2) Canver, M.C., Smith, E.C., Sher, F., Pinello, L., Sanjana, N.E., Shalem, O., Chen, D.D., Schupp,
P.G., Vinjamur, D.S., Garcia, S.P., Luc, S., Kurita, R., Nakamura, Y., Fujiwara, Y., Maeda, T.,
Yuan, G.C., Zhang, F., Orkin, S.H., and Bauer, D.E. BCL11A enhancer dissection by Cas9mediated in situ saturating mutagenesis.  Nature 527: 192-197 (2015)
3) Kurita, R., Suda, N., Sudo, K., Miharada, K., Hiroyama, T., Miyoshi, H., Tani, K., andNakamura, Y. Establishment of immortalized human erythroid progenitor cell lines able toproduce enucleated red blood cells.  PLoS ONE 8: e59890 (2013)
4) Hiroyama, T., Miharada, K., Sudo, K., Danjo, I., Aoki, N., and Nakamura,Y. Establishment ofmouse embryonic stem cell-derived erythroid progenitor cell lines able to produce functional red
blood cells.  PLoS ONE 3: e1544 (2008)
5) Miharada, K., Hiroyama, T., Sudo, K., Nagasawa, T., and Nakamura, Y. Efficient enucleationof erythroblasts differentiated in vitro from hematopoietic stem and progenitor cells.   Nat.
Biotechnol. 24: 1255-1256 (2006)

40

Principal Investigator
E-mail address
URL

Professor and Director General Keiji Tanaka

tanaka-kj@igakuken.or.jp

http://www.igakuken.or.jp/

Tanaka. K

Biochemistry and Molecular Cell Biology

Other Faculty Members
Project leader, Noriyuki Matsuda; Chief Researcher, Yasushi Saeki; Senior Researcher,
Yukiko Yoshida; Senior Researcher; Kei Okatsu

Major Scientific Interests of the Group
In-depth analyses of ubiquitin-, proteasome-, and autophagy-mediated regulatory proteolysis.
Projects for Graduate Students
1) Molecular mechanisms for assembly and diversity in eukaryotic proteasomes.
2) Physiological and Pathological roles of the autophagy system.
3) Control of mitochondrial homeostasis by PINK1/Parkin whose impairment causes Parkinson’s disease.
Study Programs for Short Stay Students (one week ~ one trimester)1) Enzymatic assays and affinity purification of eukaryotic proteasomes.
2) Ubiquitylation assays directed by Parkin and SCFFbs ubiquitin E3 ligases.
3) Assays for monitoring autophagy based on genetically engineered mice.
Recent Publications
1) Pack, Chan-Gi., Yukii, H., Toh-e, A., Kudo, T., Tsuchiya, H., Kaiho, A., Sakata, E., Murata, S.,
Yokosawa, H., Sako, Y., Baumeister, W., Tanaka, K., and Saeki, Y. (2014) Quantitative live-cell imaging
reveals molecular dynamics and cytoplasmic assembly of the 26S proteasome. Nat Commun. in press.
2) Ichimura, Y., Waguri, S., Sou, Y., Kageyama, S., Hasegawa, J., Ishimura, R., Saito, T., Yang, Y., Kouno, T.,
Fukutomi, T., Hoshii, T., Atsushi, H., Takagi, K., Mizushima, T., Motohashi, H., Lee, M-S., Yoshimori, T.,
Tanaka, K.*, Yamamoto, M.*, and Komatsu, K.* (2013) Phosphorylation of p62 activates the Keap1-Nrf2
pathway during selective autophagy. *cocorespondences Mol Cell 51, 618- 631.
3) Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H, Tani N, Kimura M, Go E, Koyano F, Funayama M,
Shiba-Fukushima K, Sato S, Shimizu H, Fukunaga Y, Taniguchi H, Komatsu M, Hattori N, Mihara K,
Tanaka K, and Matsuda N. (2012) PINK1 autophosphorylation upon membrane potential dissipation isessential for Parkin recruitment to damaged mitochondria. Nat Commun. 2012; 3: 1016. doi: 10.1038/
ncomms2016.
4) Sakata, E., Stengel, F., Fukunaga, K., Zhou, M., Saeki, Y., Förster, F., Baumeister, W.*, Tanaka, K.*, andRobinson, CV.* (2011) The catalytic activity of Ubp6 enhances maturation of the proteasomal regulatory
particle. *correspondences Mol. Cell 42, 637-649.
5) Matsuda, N., Sato, S., Shiba, K., Okatsu, K., Saisho, K., Gautier, CA Sou, Y., Saiki, S., Kawajiri, S., Sato, F.,
Kimura, M., Komatsu, M., Hattori, N., and Tanaka, K. (2010) PINK1 stabilized by depolarization recruits
Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 189, 211-221
6) Saeki, Y., Toh-e, A., Kudo, T., Kawamura, H., and Tanaka, K. (2009) Multiple proteasome-interacting
proteins assist the assembly of the yeast 19S regulatory particle. Cell 137, 900-913
7) Murata, S., Sasaki, K., Kishimoto, T., Niwa, S., Hayashi, H., Takahama, Y., and Tanaka, K. (2007)
Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 316, 1349-1353
8) Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Ueno, T., Koike, M., Uchiyama, Y., Kominami,E., and Tanaka, K. (2006) Loss of autophagy in the central nervous system causes neurodegeneration.
Nature 441, 880-884
9) Hirano, Y., Hendil, K.B., Yashiroda, H., Iemura, S., Nagane, R., Hioki, Y., Natsume, T., Tanaka, K., and
Murata, S. (2005) A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes.
Nature 437, 1381-1385.

41

Kano. S

International Medicine
Principal Investigator
E-mail address
URL

Prof. Shigeyuki Kano

kano@ri.ncgm.go.jp

http://www.rincgm.jp/en/department/lab/01/

Other Faculty Member
Associate Prof. Takashi Hamabata: thama@ri.ncgm.go.jp

Major Scientific Interests of the GroupThe objectives of our research group are to develop appropriate medical technologies that aretransferable to developing countries, in order to promote their primary health status. The following
two subjects are our biggest research targets.
1) Research on controlling emerging and re-emerging infectious diseases of international importance.
2) Research on international medical cooperation.
Projects for Regular Students in Doctoral or Master’s Programs
1) Biology and pathophysiology of re-emerging infectious diseases(a) Basic and clinical research on malaria(b) Research on the development of malaria vaccine
2) Social technology development for controlling diseases in developing countries(a) Researches on global malaria and parasite control strategy(b) Evaluation of international health cooperation projects
Training Programs for Short Stay Students (one week ~ one trimester)1) In vitro culture of Plasmodium falciparum and its drug susceptibility assay
2) Discrimination of parasite species by PCR and other methods, including drug resistant DNA marker
detection.
Recent Publications
1) Kimura R, Komaki-Yasuda K, Kawazu S, Kano S. 2-Cys peroxiredoxin of Plasmodium falciparum is
involved in resistance to heat stress of the parasite. Parasitol Int 62:137-43, 20132) Iwagami M, Fukumoto M, Hwang SY, Kim SH, Kho WG, Kano S: Population structure andtransmission dynamics of Plasmodium vivax in the Republic of Korea based on microsatellite DNA
analysis. PLoS Negl Trop Dis, 6(4):e1592, 20123) Culleton R, Coban C, Zeyrek FY, et al: The origins of African Plasmodium vivax; Insights frommitochondrial genome sequencing. PLoS ONE 6(12): e29137, 2011
4) Okudaira N, Goto M, Yanobu-Takanashi R, et al.: Involvement of retrotransposition of longinterspersed nucleotide element-1 in skin tumorigenesis induced by 7,12-dimethylbenz[a]anthracene
and 12-O-tetradecanoylphorbol-13-acetate. Cancer Science 102(11): 2000-6, 201142

Principal Investigator
E-mail address
URL

Prof. Ichiro Kuranekurane@nih.go.jp

http://www.nih.go.jp/niid/index.html

Kurane. I

Virology

Major Scientific Interests of the Group

Elucidation of the pathogenesis of dengue fever and dengue hemorrhagic fever.
Projects for Regular Students in Doctoral or Master’s Programs
1) Establishment of animal models of dengue fever.
2) Role of immune responses in the pathogenesis of dengue hemorrhagic fever.
Training Programs for Short Stay Students (one week ~ one trimester)
None
Recent Publications
1) Moi, M.L., Lim,C.K., Kotaki, A., Takasaki, T. and Kurane, I.: Detection of higher levels of dengue
viremia using Fc{gamma}R-expressing BHK-21 cells than Fc{gamma}R-negative cells in secondary
infection but not in primary infection. Journal of Infectious Diseases. 203(10): 1405-1414, 2011.
2) Fujii, K., Matsutani, T., Kitaura, K., Suzuki, S., Itoh, T., Takasaki, T., Suzuki, R. and Kurane, I.:
Comprehensive analysis and characterization of the TCR alpha chain sequences in the common
marmoset. Immunogenetics, 62(6): 383-385, 2010.
3) Tajima, S., Nerome, R., Nukui, Y., Kato, F, Takasaki, T. and Kurane, I.: A single mutation in theJapanese encephalitis virus E protein (S123R) increases its growth rate in mouse neuroblastoma cells
and its pathogenicity in mice. Virology 396(2): 298-304, 2010.
4) Moi, M.L., Lim, C.K., Takasaki, T. and Kurane, I.: Involvement of the Fc gamma receptor IIA  
cytoplasmic domain in antibody-dependent enhancement of dengue virus infection. Journal of
General Virology 91(Pt 1): 103-111, 2010.
5) Moi, M.L., Lim, C.K., Kotaki, A., Takasaki, T. and Kurane, I.: Discrepancy in neutralizing antibody
titers between plaque reduction neutralizing tests with Fcgamma receptor (Fcgamma R)-negative andFcgammaR-expressing BHK-21 cells. Clinical and Vaccine Imunology 17(3): 402-7,2010.
6) Lim, C.K., Nishibori, T., Watanabe, K., Ito, M., Kotaki, A., Tanaka, K., Kurane, I. and Takasaki, T.:
Chikungunya virus isolated from a returnee to Japan from Sri Lanka: isolation of two sub-strains withdifferent characteristics. American Journal of Tropical Medicine and Hygiene 81(5): 865-8, 2009.
7) Moi, M.L., Lim, C.K., Kotaki, A., Takasaki, T. and Kurane, I.: Development of an antibodydependent enhancement assay for dengue virus using stable BHK-21 cell lines expressing Fc
gammaRIIA. Journal of Virological Methods 163(2)205-9, 2010.

43

Notes