Research Fields

PI

page

University of Tsukuba
1. Anatomy and Embryology

Takahashi S

1

2. Laboratory Animal Science

Yagami K

2

3. Physiological Chemistry

Kanaho Y

3

4. Molecular Cell Biology

Irie K4

5. Gene Regulation

Hisatake K

5

6. Molecular Cell Physiology

Okamura N

6

7. Molecular Neurobiology

Masu M

7

8. Medical Genetics

Arinami T

8

9. Molecular Pharmacology

Yanagisawa M

910. Diagnostic Pathology

Noguchi M

10

11. Experimental Pathology

Kato M

11

12. Kidney and Vascular Pathology

Nagata M

12

13. Infection Biology

Nagata K

13

14. Immunology

Shibuya A

14

15. Regenerative Medicine andOhneda O

15

16. Environmental Medicine

Kumagai Y

16

17. Genetic Epidemiology/

Tsuchiya N

17

18. Occupational Psychiatry/ Space Medicine Matsuzaki I

18

19. Radiation Biology

Tsuboi K

19

20. Functional Genomics

Ishii S

20

21. International Medicine

Kano S21

22. Virology

Kurane I

22

23. Experimental Hematology

Nakamura Y

23

24. Biochemistry and Molecular Biology

Tanaka K

24

Stem Cell Biology

Public Health Medicine

Cooperative Graduate Programs

University of Tsukuba

Name of the Field: Anatomy and Embryology/
Laboratory Animal Resource Center
Principal Investigator: Satoru Takahashi
E-mail address: satoruta@md.tsukuba.ac.jp
URL: 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.
We are researching the molecular mechanisms of the development of pancreatic endocrine
cells and macrophages. By analyzing the function of the large Maf family of transcription
factors. In both human and mouse, four large Maf transcription factors, MafA, MafB, c-Maf
and Nrl, have been identified.
2) Analysis about molecular mechanism of stem cell pluripotency.
In addition to these themes, we are also analyzing molecular mechanism of stem cell
pluripotency.

Study Programs for Short Stay Students (one week ~ one trimester)3) Histological analysis of genetically manipulated mice.
4) Handling skill for mouse embryos.
Recent Publications
1) Takase H, Yamadera R, Matsumoto K, Kubota Y, Ohtsu A, Suzuki R, Kojima T, Mochizuki H,
Ishitobi H, Takano S, Uchida K, Takahashi S, Ema M. Genome-wide identification ofvascular endothelial-specific genes during development in the mouse. Blood. 120, 914-923.
2) 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 ofdefinitive erythropoiesis as it forms erythroblastic islands in fetal liver. Blood. 118,
1374-1385, 2011.
3) Hishida T, Nozaki Y, Nakachi Y, Mizuno Y, Okazaki Y, Ema M, Takahashi S, Nishimoto M,
Okuda A. Indefinite self-renewal of ES cells through Myc/Max transcriptional
complexes-independent mechanisms. Cell Stem Cell. 9, 37-49, 2011.
4) Morito N, Yoh K, Maeda A, Nakano T, Fujita A, Kusakabe M, Hamada M, Kudo T, Yamagata
K, Takahashi S. A novel transgenic mouse model of the human multiple myeloma
chromosomal translocation t(14;16)(q32;q23). Cancer Res. 71, 339-348, 2011.
5) 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 cell differentiation. J Clin Invest. 120, 3455-3465, 2010.

1

University of Tsukuba

Research Field: Laboratory Animal Science
Principal Investigator: Prof. Ken-ichi Yagami
E-mail address: kenyagam@md.tsukuba.ac.jp
URL: http://www.md.tsukuba.ac.jp/basic-med/yagami/index.html
Other Faculty Members
Associate Professor Fumihiro Sugiyama: bunbun@md.tsukuba.ac.jp
Assistant Professor Satoshi Kunita: kunitasa@md.tsukuba.ac.jp
Major Scientific Interests of the GroupThe aims of our research are development, characterization and quality control of geneticallyinduced animal models for human diseases. We focus on the following research themes:
1) We are creating a variety of mice in which genes regulating blood pressure (BP) are altered.
Characterization of these mice allows us to develop hypertension models as well as toevaluate unknown functions of the genes. Additionally, quantitative trait loci (QTL) mappingof BP regulating genes is in progress by using spontaneously hypertensive mice to searchnovel genes associated with BP regulation.
2) In order to elucidate the molecular mechanisms associated with pathogenesis of infectious
agents, such as parvovirus and Helicobacter, we are analyzing the interaction between
infectious agents and host genes. Additionally, we continue to develop technology forcreating genetically-induced mice and to survey microbiological infection in laboratory
animals.
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Programs
1) Development of embryonic stem cells in mice and rats.
2) Development of monoclonal antibody-based antigen detection methods for diagnosing
infectious diseases in mice (such as Helicobacter hepaticus and murine norovirus infections).
Training Programs for Short Stay Students (one week ~ one trimester)1) Manipulation of mouse preimplantation embryos.
2) Multiplex serologic tests for infectious diseases in mice and rats by microsphere fluorescentimmunoassay.
Recent Publications

1) Feng M, Deerhake ME, Keating R, Thaisz J, Xu L, Tsaih SW, Smith R, Ishige T, Sugiyama F,
Churchill GA, DiPetrillo K.Genetic analysis of blood pressure in 8 mouse intercross populations.
Hypertension. 2009 Oct;54(4):802-9. Epub 2009 Aug 3.
2) Tanimoto Y, Iijima S, Hasegawa Y, Suzuki Y, Daitoku Y, Mizuno S, Ishige T, Kudo T, Takahashi S,
Kunita S, Sugiyama F, Yagami K. Embryonic stem cells derived from C57BL/6J and C57BL/6N
mice. Comp Med. 2008 Aug;58(4):347-52.
3) Shigematsu Y, Yoshida N, Miwa Y, Mizobuti A, Suzuki Y, Tanimoto Y, Takahashi S, Kunita S,
Sugiyama F, Yagami K. Novel embryonic stem cells expressing tdKaede protein photoconvertible
from green to red fluorescence.( Int J Mol Med. 2007 Oct;20(4):439-44)
4) Nishihara E, Tsaih SW, Tsukahara C, Langley S, Sheehan S, DiPetrillo K, Kunita S, Yagami K,
Churchill GA, Paigen B, Sugiyama F. Quantitative trait loci associated with blood pressure of
metabolic syndrome in the progeny of NZO/HILtJxC3H/HeJ intercrosses. Mamm Genome. 2007
Aug;18(8):573-83.
5) Kunita S, Chaya M, Hagiwara K, Ishida T, Takakura A, Sugimoto T, Iseki H, Fuke K, Sugiyama F,
Yagami K. Development of ELISA using recombinant antigens for specific detection of mouseparvovirus infection. Exp Anim. 2006 Apr;55(2):117-24.
6) Shimizu Y, Motohashi N, Iseki H, Kunita S, Sugiyama F, Yagami K. A novel subpopulation lacking
Oct4 expression in the testicular side population. Int J Mol Med. 2006 Jan;17(1):21-8.
7) Iseki H, Shimizukawa R, Sugiyama F, Kunita S, Iwama A, Onodera M, Nakauchi H, Yagami K.
Parvovirus nonstructural proteins induce an epigenetic modification through histone acetylation in hostgenes and revert tumor malignancy to benignancy. J Virol. 2005 Jul;79(14):8886-93.
8) Shimizukawa R, Sakata A, Hirose M, Takahashi A, Iseki H, Liu Y, Kunita S, Sugiyama F, Yagami K.
Establishment of a new embryonic stem cell line derived from C57BL/6 mouse expressing EGFP
ubiquitously. Genesis. 2005 May;42(1):47-52.

2

University of Tsukuba

Physiological ChemistryPrincipal Investigator: Yasunori Kanaho
E-mail address: ykanaho@md.tsukuba.ac.jp
URL:http: //www.md.tsukuba.ac.jp/basic-med/biochem/kanaholab/index.html
Other Faculty Members
Associate Professor Hiroshi Hasegawa: h.hasegawa@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 cell signaling systems,
especially through the phospholipid-metabolizing enzymes and the small G protein Arf6.
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Programs
1) Molecular mechanisms through which the small G protein Arf6 regulates each isozyme of thelipid kinase PIP5K.
2) Physiological functions of the phospholipid-metabolizing enzymes, PIP5K and PLD, and of
their regulatory protein Arf6 at cellular and whole animal levels.
3) Human diseases caused by the disruption of the signaling systems through thelipid-metabolizing enzymes and the small G protein Arf6.
Study Programs for Short Stay Students (one week ~ one trimester)1) Enzyme assay, immunohistochemistry, and immunofluorescent staining of signaling
molecules
2) Assays for cell functions such as cell proliferation, cell motility, focal adhesion, secretion,
endocytosis, exocytosis, etc.
Recent Publications
1) Unoki T., Matsuda S., Kakegawa W., Van TBN., Kohda K., Suzuki A., Funakoshi Y.,
Hasegawa H., Yuzaki M., and Kanaho Y. NMDA receptor-mediated PIP5K activation to
produce PI(4,5)P2 is essential for AMPA receptor endocytosis during LTD. Neuron 73,
135-148 (2012)
2) Nakano-Kobayashi A., Yamazaki M., Unoki T., Hongu T., Murata C., Taguchi R., Katada
T., Frohman M.A., Yokozeki T. and Kanaho Y. Role of activation of PIP5Kg661 by AP-2
complex in synaptic vesicle endocytosis. EMBO J. 26, 1105-1116 (2007)
3) Suzuki T., Kanai Y., Hara T., Sasaki J., Sasaki T., Kohara M., Maehama T., Taya C., Shitara
H., Yonekawa H., Frohaman M.A., Yokozeki T. and Kanaho Y. Crucial role of the small
GTPase ARF6 in hepatic cord formation during liver development. Mol. Cell. Biol. 26,
6149-6156 (2006)
4) Honda A., Nogami M., Yokozeki T., Yamazaki M., Nakamura H., Watanabe H., KawamotoK., Nakayama K., Morris A.J., Frohman M.A., and Kanaho Y. Phosphatidylinositol
4-phosphate 5-kinase a is a downstream effector of the small G protein ARF6 in membrane
ruffle formation. Cell 99,521-532 (1999)3

University of Tsukuba

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 Takahiro Naiki: taknaiki@md.tsukuba.ac.jp
Assistant Professor Tomoaki Mizuno: mizuno@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, asymmetric cell division, and cell-fate
Regulation of myogenic differentiation by RNA-binding protein
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Programs
1) Stability control of MTL1 mRNA by the RNA-binding protein Khd1p in yeast2) Post-transcriptional regulation of gene expression by Khd1, Ccr4, and Pbp1
3) Stau1 negatively regulates myogenic differentiation in C2C12 cells.
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 generationof mutations in cloned genes.
3) Imaging yeast cells using indirect immunofluorescence and GFP-protein fusions.
Recent Publications
1) Stau1 regulates Dvl2 expression during myoblast differentiation. Yamaguchi Y, Naiki T, Irie
K. Biochem Biophys Res Commun. 2012 Jan 6;417(1):427-32.
2) RNA-binding protein Khd1 and Ccr4 deadenylase play overlapping roles in the cell wall
integrity pathway in Saccharomyces cerevisiae. Ito W, Li X, Irie K, Mizuno T, Irie K.
Eukaryot Cell. 2011 Oct;10(10):1340-7.
3) Stability control of MTL1 mRNA by the RNA-binding protein Khd1p in yeast. Mauchi N,
Ohtake Y, Irie K. Cell Struct Funct. 2010;35(2):95-105.
4) hnRNP K interacts with RNA binding motif protein 42 and functions in the maintenance of
cellular ATP level during stress conditions. Fukuda T, Naiki T, Saito M, Irie K. Genes Cells.
2009 Feb;14(2):113-28.
5) Distinct roles for Khd1p in the localization and expression of bud-localized mRNAs in yeast.
Hasegawa Y, Irie K, Gerber AP. RNA. 2008 Nov;14(11):2333-47.
6) Stau1 negatively regulates myogenic differentiation in C2C12 cells. Yamaguchi Y, Oohinata
R, Naiki T, Irie K. Genes Cells. 2008 Jun;13(6):583-92.

4University of Tsukuba

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/
Major Scientific Interests of the GroupOur group studies the regulation of eukaryotic gene expression,
focusing on how transcription regulates cell differentiation. In
particular, we are studying the roles of transcription factors andepigenetic changes in regulating iPS cell induction and adipocyte
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 induction.
2) Analyses of epigenetic mechanisms of iPS cell induction.
3) Identification and functional analyses of transcription factors involved in adipocyte
commitment.
4) Role of non-coding RNA in epigenetic regulation during adipocyte differentiation.
Study Programs for Short Stay Students (one week ~ one trimester)1) Analysis of transcriptional regulation during white and brown adipocyte differentiation.
2) Induction of iPS cells using a Sendai virus-based vector.
Recent Publications
1) Shimada M, Nakadai T, Fukuda A, Hisatake K. cAMP-response element-binding protein(CREB) controls MSK1-mediated phosphorylation of histone H3 at the c-fos promoter in vitro.
J. Biol. Chem. 285, 9390-9401, 2010
2) Chen Y, Yamaguchi Y, Tsugeno Y, Yamamoto J, Yamada T, Nakamura M, Hisatake K,
Handa H. DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles in RNA
polymerase II elongation. Genes Dev. 23, 2765-2777, 2009.
3) Fukuda A, Nakadai T, Shimada M, Hisatake K. Heterogeneous nuclear ribonucleoprotein R
enhances transcription from the naturally configured c-fos promoter in vitro. J. Biol. Chem.
284, 23472-23480, 2009.
4) Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, Mukai H, Kasuya Y,
Fukamizu A. Arginine methylation of FOXO transcription factors inhibits theirphosphorylation by Akt. Mol. Cell 32, 221-231, 2008.
5) Fukuda A, Nakadai T, Shimada M, Tsukui T, Matsumoto M, Nogi Y, Meisterernst M,
Hisatake K. Transcriptional coactivator PC4 stimulates promoter escape and facilitatestranscriptional synergy by GAL4-VP16. Mol. Cell. Biol. 24, 6525-6535, 2004.

5

University of Tsukuba

Molecular Cell Physiology / Reproductive BiochemistryPrincipal Investigator: Naomichi Okamura
E-mail address: naooka@md.tsukuba.ac.jp
URL: http://www.md.tsukuba.ac.jp/basic-med/biochem/reproductive_biochem/index.html
Other Faculty Members
Assistant Professor: Manabu Matsuda,
Akihiro Kawashima
Major Scientific Interests of the Group
1. Molecular mechanisms involved in the spermatogenesis andsperm maturation in mammals
2. Signal transduction in germ cells
3. Biology of mammogenesis, milkstasis and secretion
Projects for Regular Students in Doctoral or Master’s  Programs
1) Proteome analysis of calcium-binding proteins expressed in the spermatogenic cells.
2) Molecular mechanisms of the sperm maturation during transit through epididymis.
3) Role of the protein tyrosine phosphorylation in capacitation.
Study Programs for Short Stay Students (one week ~ one trimester)
1) Technology for proteome analysis.
2) Assessment of mammalian sperm fertilizing activities.
3) In vitro studies on functions of monoamines in secretion.
Recent Publications
9) Osman B, Kawashima A, Tamba M, Satoh E, Kato Y, Iki A, Konishi K, Matsuda M and Okamura N.
Localization of a Nobel RNA-binding Protein, SKIV2L2, to the Nucleus in the Round Spermatids ofMice. J. Reprod. Develop., 57, 457-467, 2011.
10) Ogushi Y, Akabane G, Hasegawa T, Mochida H, Matsuda M, Suzuki M, Tanaka S. Water adaptation
strategy in anuran amphibians: molecular diversity of aquaporin. Endocrinology 151(1), 165-173,
2010.
11) Kawashima A, Osman B, Takashima M, Kikuchi A, Kohch S, Satoh E, Tamba M, Matsuda M andOkamura N. CABS1 is a novel calcium-binding protein specifically expressed in elongate spermatidsof mice. Biol. Reprod.,80, 1293-1304, 2009.

6

University of Tsukuba

Research Field: 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:
TakuyaOkada:
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 thatplay a role in neural differentiation, 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
Recent Publications
1) Nagamine S et al. Organ-Specific Sulfation Patterns of Heparan Sulfate Generated byExtracellular Sulfatases Sulf1 and Sulf2 in Mice. J Biol Chem 287: 9579-9590, 2012.
2) Koike S, Yutoh Y, Keino-Masu K, Noji S, Masu M, and Ohuchi H. Autotaxin is required forthe cranial neural tube closure and establishment of the midbrain-hindbrain boundary during
mouse development. Dev Dyn 240: 413-421, 2011.
3) Koike S, Keino-Masu K, Ohto T, Sugiyama F, Takahashi S, and Masu M.
Autotaxin/lysophospholipase D-mediated LPA Signaling is Required to Form Distinctive
Large Lysosomes in the Visceral Endoderm Cells of the Mouse Yolk Sac. J Biol Chem 284:
33561-33570, 2009.
4) 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.
5) Keino-Masu K, Masu M, et al. Deleted in Colorectal Cancer (DCC) Encodes a Netrin
Receptor. Cell 87: 175-185, 1996.

7

University of Tsukuba

Medical Genetics
Principal Investigator: Tadao Arinami
E-mail address: tarinami@md.tsukuba.ac.jp
URL: http://www.md.tsukuba.ac.jp/basic-med/m-genetics/
Major Scientific Interests of the Group1) Genetic study of neuropsychiatric disorders. Linkage and association analyses, expression
profiles from human and animal tissues, and animal model study of schizophrenia, depression,
substance abuse/dependence, developmental disorders.
2) Genetic study of asthma/allergy. Linkage and association analyses, expression profiles fromhuman and animal tissues, and animal model study of bronchial asthma, allergic rhinitis andatopic dermatitis.
3) Genetic diagnosis and counseling
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Programs  1) Molecular pathophysiology and therapeutic trials for schizophrenia, depression anddevelopmental disorders based on genetic evidence.
2) Identification of novel genomic mutations associated with asthma/atopy and development ofgenetic markers and therapeutic materials for personalized medicine of asthma and pollinosis.
Study Programs for Short Stay Students (one week ~ one trimester)
1) Genetic testing, genotyping, expression analyses,
2) Genetic informatics
Recent Publications
1) Tanaka S, Syu A, Ishiguro H, Inada T, Horiuchi Y, Ishikawa M, Koga M, Noguchi E,
Ozaki N, Someya T, Kakita A, Takahashi H, Nawa H, Arinami T. DPP6 as a candidate
gene for neuroleptic-induced tardive dyskinesia. Pharmacogenomics J. in press
2) 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. Genome-wide association study identifies HLA-DP as asusceptibility gene for pediatric asthma in Asian populations. PLoS Genet 7:e1002170,
20113) Syu A, Ishiguro H, Inada T, Horiuchi Y, Tanaka S, Ishikawa M, Arai M, Itokawa M,
Niizato K, Iritani S, Ozaki N, Takahashi M, Kakita A, Takahashi H, Nawa H, Keino-Masu
K, Arikawa-Hirasawa E, and Arinami T. Association of the HSPG2 gene withneuroleptic-induced tardive Dyskinesia. Neuropsychopharmacology. 35:1155-1164, 2010
Ishiguro H, Horiuchi Y, Ishikawa M, Koga M, Imai K, Suzuki Y, Morikawa M, Inada T,
Watanabe Y, Takahashi M, Someya T, Ujike H, Iwata N, Ozaki N, Onaivi ES, Kunugi H, Sasaki
T, Itokawa M, Arai M, Niizato K, Iritani S, Naka I, Ohashi J, Kakita A, Takahashi H, Nawa H,
and Arinami T. Brain cannabinoid CB2 receptor in schizophrenia. Biol Psychiatry. 67:974-982.
20108

University of Tsukuba

Name of the Field: Molecular Pharmacology
Principal Investigator: Masashi Yanagisawa, M.D., Ph.D.
E-mail address: yanagisawa.masa.fu@u.tsukuba.ac.jp
URL: http://sleepymouse.tsukuba.ac.jp/
Other Faculty Member:
Associate Professor Hiromasa Funato, M.D., Ph.D.
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 responsible for sleep/wake regulation in
mutagenized mice2) Chemical biology for orexin receptor agonists
3) Analysis of sleep and wakefulness in genetically modified mice4) In vivo real-time imaging of neuronal activities in the hypothalamus and other deep brain
structures 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 slices4) Cell-based assay for GPCR activation
Recent Publications
1) Funato H, Sato M, Sinton CM, Gautron L, Williams SC, Skach A, Elmquist JK, Skoultchi AI,
Yanagisawa M.Loss of Goosecoid-like and DiGeorge syndrome critical region 14 ininterpeduncular nucleus results in altered regulation of rapid eye movement sleep. Proc Natl
Acad Sci U S A. 2010 Oct 19;107(42):18155-60. Epub 2010.
2) Matsuki. T., Nomiyama, M., Takahira, H., Hirashima. N., Kunita, S., Takahashi, S., Yagami, K.,
Kilduff, T.S., Bettler, B., Yanagisawa, M. & Sakurai, T. Selective loss of GABAB receptors in
orexin-producing neurons results in disrupted sleep/wakefulness architecture. Proc. Natl.
Acad. Sci. USA 106:4459-64, 2009.
3) Irukayama-Tomobe, Y., Tanaka, H., Yokomizo, T., Yanagisawa, M. & Sakurai, T. AromaticD-amino acids act as chemoattractant factors for human leukocytes through a G
protein-coupled receptor, GPR109B. Proc. Natl. Acad. Sci. USA 106:3930-4, 2009.
4) Sakakibara,I., Fujino, T., Ishii, M., Tanaka,T., Shimosawa, T., Miura, S., Zhang,
W.,Tokutake,8 Y., Yamamoto, J., Awano, M., Iwasaki, S., Motoike, T., Okamura, M., Inagaki,T., Kita, K., Ezaki, O., Naito, M., Kuwaki, T., Chohnan, S., Yamamoto, T., Hammer, R.E.,
Kodama, T., Yanagisawa, M., and Sakai, J. Fasting-Induced Hypothermia and Reduced
Energy Production in Mice Lacking Acetyl-CoA Synthetase 2 Celll Metabolism 9: 191-202.
2009.
5) Funato, H., Tsai, A.L., Willie, J.T., Kisanuki Y., Williams,S.C., Sakurai,T., and Yanagisawa M.
Enhanced Orexin Receptor-2 Signaling Prevents Diet-Induced Obesity and Improves Leptin
Sensitivity. Celll Metabolism 9: 64-76. 2009.

9University of Tsukuba

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 Yukio Morishita:ymorishi@md.tsukuba.ac.jp
Associate Professor Yuko Minami: minami-y@md.tsukuba.ac.jp
Assistant Professor Junko Kano: junkano@md.tsukuba.ac.jp
Assistant Professor Shingo Sakashita: sakashingo@hotmail.com
Assistant Professor Kaishi Satomi: kaishis@md.tsukuba.ac.jp
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 pulmonary adenocarcinogenesis. Screening of thedifferentially expressed genes and proteins between early adenocarcinoma of the lung (insitu adenocarcinoma) and early advanced tumors.
2) Produce monoclonal antibodies against fetal swine to screen for specific antibodies against
human carcinomas.
3) In vitro and in vivo studies of the molecular mechanisms of the reproduction of liver tissue.
Study Programs for Short Stay Studies (one week 〜 one trimester)1) Basic techniques of immunohistochemistry, in situ hybridization, and FISH
2) Basic techniques of tissue micro-dissection
Recent Publications
1) Shiba-Ishii A and Noguchi M. Aberrant Stratifin overexpression is regulated bytumor-associated CpG demetylation in lung adenocarcinoma. Am J Pathol 180:1653-1662,
2012.
2) Tachibana K, Minami Y, Shiba-Ishii A, Kano J, Nakazato Y, Sato Y, Goya T and Noguchi M.
Abnormality of the hepatocyte growth factor/MET pathway in pulmonary
adenocarcinogenesis. Lung Cancer 75:181-188, 2012.
3) Satomi K, Morishita Y, Sakashita S, Kondou Y Furuya S, Minami Y and Noguchi M.
Specific expression of ZO-1 and N-cadherin in rosette structures of various tumor: possible
recapitulation of neural tube formation in embryogenesis and utility as a potentially novel
immunohistochemical marker of rosette formation in pulmonary neuroendocrine tumors.
Virchow Arch 459:399-407, 2011.
4) Li D, Sakashita S, Morishita Y, Kano J, Shiba A, Sato T and Noguchi M. Binding oflactoferrine to IGBP1 triggers apoptosis in a lung adenocarcinoma cell line. ANTICANCERRESEARCH 31:529-534, 2011.
5) Kobayashi H, Minami Y, Anami Y, Kondou Y, Iijima T, Kano J, Morishita Y, Tsuta K,
Hayashi S and Noguchi M. Expression of the GA733 gene family and its relationship toprognosis in pulmonary adenocarcinoma. Virchows Arch 457:69-76, 2010.
6) Nakazato Y, Minami Y, Kobayashi H, Satomi K, Anami Y, Tsuta K, Tanaka R, Okada M,
Goya T and Noguchi M. Nuclear Grading of Primary Pulmonary Adenocarcinomas-Correlation of nuclear size with prognosis-. Cancer 116:2011-2019, 2010.
7) Anami Y, Iijima T, Suzuki K, Yokota J, Minami Y, Kobayashi H, Satomi K, Nakazato Y,
Okada M and Noguchi M. Bronchioloalveolar carcinoma (lepidic growth) component is amore useful prognostic factor than lymph node metastasis. J Thorac Oncol 4:951-8, 2009.

10

University of Tsukuba

Experimental Pathology
Principal Investigator: Mitsuyasu Kato
E-mail address: mit-kato@md.tsukuba.ac.jp
URL: http://www.md.tsukuba.ac.jp/epatho/
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 Group
Experimental studies, using murine models and cultured cells, for elucidation of the roles oftransforming growth factor- related molecules in stem cell biology, tissue formation andcarcinogenesis. Our aim is to establish novel molecular targeting therapies useful for theprevention of cancer.
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Programs
1) Molecular mechanisms of TGF- related molecules (TMEPAI, MafK etc.) in colonic stem
cells maintenance and carcinogenesis using gene-manipulated mice and three dimensional
histopathological analysis.
2) Molecular mechanisms of TGF- related molecules (THG1 etc.) in squamous cell carcinoma
formation
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 forming assay, scratch assay, matrigel
invasion assay, 3D culture invasion assay etc.)
Recent Publications
1) 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 in press.
2) 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--inducible protein, sequesters Smad proteins from active participationin TGF-b signaling. Mol. Cell 37: 123-134, 2010.
3) Nakano N, Itoh S, Watanabe Y, Maeyama K, Itoh F, and Kato M. Requirement of TCF7L2
for TGF--dependent transcriptional activation of the TMEPAI gene. J Biol Chem. 285:
38023-38033, 2010.
4) 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.
5) Shi L, Itoh F, Itoh S, Takahashi S, Yamamoto M and Kato M. Ephrin-A1 promotes themalignant progression of intestinal tumors in Apcmin/+ mice. Oncogene 27(23): 3265-3273,
2008.

11

University of Tsukuba

Research Field: 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 (ANCA-related) and cystogenesis inpolycystic 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 theview 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 usefuldiagnostic 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 amurine
model
of
focal
segmental
glomerulosclerosis.
Am
J
Pathol2009May;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 acidtransporter 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: ahistological and diagnostic marker for mitochondrial nephropathy Am J Sur Pathol 34:
262-70, 201012

University of Tsukuba

Infection Biology
Principal Investigator: Professor Kyosuke Nagata
E-mail address: knagata@md.tsukuba.ac.jp
URL: http://www.md.tsukuba.ac.jp/basic-med/infectionbiology/
virology/index_english.html
Other Faculty Members:
Associate Professor; Kaoru Takeuchi, Mitsuru Okuwaki
Assistant Professor; Shoko Saito, Kohsuke Kato, Atsushi Kawaguchi
Major Scientific Interests of the Group:
The research aim of this group is to understand the molecular mechanism of replication andpathogenicity of animal viruses such as influenza viruses, measles virus, adenovirus, humancytomegalovirus, etc. The structure and function of virus-encoded factors and hostcell-derived factors involved in the above processes are being studied at the atomic, molecular,
cellular, and body levels. In addition, we are particularly interested in clarifying thephysiological 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 throughdevelopment of novel anti-viral drugs
3) Regulatory mechanism for the structure and function of chromatin4) Leukemogenic mechanism by chromosomal translocation
Study Programs for Short Stay Students (one week ~ one trimester):1) Discovery of novel factors using an influenza virus replicon system in yeast2) Action mechanism of an anti-virus drug3) Cell-free reconstitution of a nucleus
4) Molecular function of a fusion gene product(s) in oncogenesis
Selected Recent Publications:
1) Kohsuke Kato, Mitsuru Okuwaki, Nagata K. Involvement of Template Activating Factor-I
as a chaperone in linker histone dynamics. J. Cell Sci., 2011; 124: 3254-3265.
2) Sugiyama K, Obayashi E, Kawaguchi A, Tame J R H, Nagata K, Park S-Y. Structural
insight into a novel subunit contact within influenza virus RNA polymerase. EMBO J., 2009;
28: 1803-1811.
3) 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.
4) Naito T, Kiyasu Y, Sugiyama K, Kimura A, Nakano R, Matsukage A, Nagata K. A novel
influenza virus replicon system in yeast identified Tat-SF1 as a stimulatory host factor for viral
RNA synthesis. Proc. Natl. Acad. Sci. USA, 2007; 104: 18235-18240.
5) Kawaguchi A, Nagata K. De novo replication of the influenza virus RNA genome is regulated
by a DNA replicative helicase, MCM. EMBO J., 2007; 26: 4566-4575.
6) Haruki H, Okuwaki M, Miyagishi M, Taira K, Nagata K. Involvement of TAF-I/SET intranscription of adenovirus early genes as a positively acting factor. J. Virol., 2006; 80:
794-801.

13

University of Tsukuba

Immunology
Principal Investigator (Professor): Akira Shibuya, M.D., Ph.D
E-mail address: ashibuya@md.tsukuba.ac.jp
URL:http://www.md.tsukuba.ac.jp/basic-med/immunology/
immunol.index.html
Other Faculty Members
Associate Professor: Kazuko Shibuya, M.D., Ph.D
(kazukos@md.tsukuba.ac.jp）
Shinichiro Honda, M.D., Ph.D (shonda@md.tsukuba.ac.jp)
Assistant Professor: Satoko Tahara, Ph.D（tokothr@md.tsukuba.ac.jp）
Chigusa Oda, M.D., Ph.D（chigusano@md.tsukuba.ac.jp）
Major Scientific Interests of the GroupThe molecular mechanisms of tumor immunity, autoimmunity, infectious immunity andallergy and clinical 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,
and Allergin-1, all of which were identified in our laboratory, in immune responses
2) The pathophysiological roles of the immunoreceptors in tumors, autoimmune diseases,
allergy and infectious disease
Study Programs for Short Stay Students (one week ~ one trimester)
1) Generation of monoclonal antibodies and their application for expression analyses by flow
cytometry and immunohistochemistry2) Cell separation by sorting on flow cytometry or magnetic beads and analyses of cytokine
production or proliferation upon antigen stimulation
Recent Publications
1) 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. in press(2012)
2) Nakano-Yokomizo T, Tahara-Hanaoka S, Nakahashi-Oda C, Nabekura T, Tchao N K,
Kadosaki M, Totsuka N, Kurita N, Nakamagoe K, Tamaoka A, Takai T, Yasui T, Kikutani
H, Honda S, Shibuya K, Lanier L L and Shibuya A. The immunoreceptor adapter protein
DAP12 suppresses B lymphocyte-driven adaptive immune responses. J. Exp. Med. 208,
1661-1671, 2011.
3) Hitomi K, Tahara-Hanaoka S, Someya S, Fujiki A, Tada H, Sugiyama T, Shibayama S,
Shibuya K and Shibuya A. An immunoglobulin-like receptor, Allergin-1, inhibits
immunoglobulin E-mediated immediate hypersensitivity reactions. Nat Immunol. 11:
601-607, 20104) Honda S, Miyamoto A, Cho Y, Usui K, Kurita N, Takeshita K, Takahashi S, Kinoshita T,
Fujita T, Tahara-Hanaoka S, Shibuya K, Shibuya A. Enhanced humoral immune responses
against T-independent antigens in Fcα/μR-deficient mice. Proc Natl Acad Sci USA.
106:11230-11235, 200914

University of Tsukuba

Regenerative Medicine and Stem Cell Biology
Principle 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
Dr. Masumi Kuma Nagano (Assistant Professor), naganom@md.tsukuba.ac.jp
Dr. Georgina Salazar (Assistant Professor), georgina.salazar@gmail.com

Major Scientific Interests of the Group:1) Identification and analyses of functional stem cells for cell therapy in human tissues
2) 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 (2012)♦
1) Basic Radiobiology for Mesenchymal stem cells
2) Neural Differentiation of human iPS for clinical use

Recent Publications:1) 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 inre-endothelialization. J Cell Physiol. 2011; 226: 224-235.
2) Nagano M, Kimura K, Yamashita T, Ohneda K, Nozawa D, Hamada H, Yoshikawa H, Ochiai N, and Ohneda 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.
3) Yamashita T, Ohneda O, Sakiyama A, Iwata F, Ohneda K, and Fujii-Kuriyama Y.

The microenvironment forerythropoiesis is regulated by HIF-2alpha through VCAM-1 in endothelial cells. Blood 2008; 112: 1482-1492.
4) Yamashita T, Ohneda K. Nagano M, Miyoshi C, Kaneko N, Miwa Y, Yamamoto M, Ohneda O, andFujii-Kuriyama Y.
ephrin A1.

HIF-2alpha in endothelial cells regulates tumor neovascularization through activation of

J Biol Chem 2008; 283: 18926-18936.

5) 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 inmice lacking a HIF-related bHLH-PAS protein NEPAS. Mol. Cell. Biol. 2008; 28: 1285-1297.
6) Nagano M, Yamashita T, Hamada H, Ohneda K, Kimura K, Nakagawa T, Shibuya M, Yoshikawa H, and Ohneda O.
Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using humanumbilical cord blood. Blood 2007; 110: 151-160.

15

University of Tsukuba

Name of the Field: Environmental Medicine
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
Assistant Professor Yasuhiro Shinkai: ya_shinkai@md.tsukuba.ac.jp
Major Scientific Interests of the Group
This laboratory addresses the mechanisms by which chemicals causing oxidative stress andenvironmental electrophiles such as polycyclic aromatic hydrocarbon quinones,
methylmercury and arsenic affect living systems by interacting with sensor proteins withreactive thiols (thiolate ions) through chemical modification. The observations obtained bythis group regarding environmental electrophiles have lent new insight into mechanisms ofredox-dependent cell signalings such as cell servival, cell proliferation and cell damage.
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Programs
1) Activation of electrophilic signal transduction pathways (e.g., PTP1B/EGFR-, Keap1/Nrf2-,
HSP/HSF-1-signalings) during exposure to environmental electrophiles such as
1,2-naphthoquinone and methylmercury.
2) Search for cellular systems regulating sensor proteins covalently modified by theenvironmental electrophiles.
Study Programs for Short Stay Students (one week ~ one trimester)1) Detection of cellular proteins modified by environmental electrophiles by Western blot
analysis with specific antibodies against the electrophiles.
2) Proteomics analysis by using 2D-SDS/PAGE and MALDI-TOF/MS.
Recent Publications
1) 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 sulfhydration. Nature Chem Biol 2012, inpress.
2) Kumagai Y, Shinkai Y, Miura T, Cho AK. The chemical biology of naphthoquinones and its
environmental implications. Annu Rev Pharmacol Toxicol 52: 221-247, 2012.
3) 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.
4) Yoshida E, Toyama T, Shinkai Y, Sawa T, Akaike T, Kumagai Y. Detoxification of methylmercury
by hydrogen sulfide producing enzyme in mammalian Cells. Chem Res Toxicol 24: 1633-1635, 2011.
5) Iwamoto N, Sumi D, Ishii T, Uchida K, Cho AK, Froines JR, Kumagai Y. Chemical knockdown ofprotein 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.

16

University of Tsukuba

Molecular and Genetic Epidemiology/Public Health Medicine
Principal Investigator: Naoyuki Tsuchiya
E-mail addresses: tsuchiya@md.tsukuba.ac.jp
URL: http://www.md.tsukuba.ac.jp/community-med/
publicmd/index.html
Other Faculty Members;
Associate Professor Jun Ohashi, juno-tky@umin.ac.jp
Assistant Professor Kazumasa Yamagishi, k-yamagishi@umin.ac.jp
Major Scientific Interests of the Group1) Genetics of human rheumatic diseases including systemic lupus erythematosus, rheumatoid
arthritis, systemic sclerosis and microscopic polyangiitis (Dr. Naoyuki Tsuchiya)
2) Genetics of obesity in Oceanic islanders (Dr. Jun Ohashi)
3) Epidemiology and prevention of lifestyle-related diseases (Dr. Kazumasa Yamagishi)
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Programs
1) Polymorphisms associated with rheumatic diseases in Japanese (Dr. Naoyuki Tsuchiya)
2) Polymorphisms associated with obesity in Oceanic populations (Dr. Jun Ohashi)
Study Programs for Short Stay Students (one week ~ one trimester)
Genome database (tutorial), SNP typing (laboratory), Preventive medicine activity in thecommunity (a field trip)
Selected Recent Publications
1) 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 multi-drug hypersensitivity marker? Ann Rheum Dis
doi:10.1136/annrheumdis-2012-201944
2) Hasebe N, Kawasaki A, Ito I, Kawamoto M, Hasegawa M, Fujimoto M, Furukawa H, Tohma
S, Sumida T, Takehara K, Sato S, Kawaguchi Y, Tsuchiya N. Association of UBE2L3
polymorphisms with diffuse cutaneous systemic sclerosis in a Japanese population. Ann
Rheum Dis 2012;71:1259-1260.
3) Hikami K, Kawasaki A, Ito I, Koga M, Ito S, Hayashi T, Matsumoto I, Tsutsumi A, Kusaoi
M, Takasaki Y, Hashimoto H, Arinami T, Sumida T, Tsuchiya N. Association of a functional
polymorphism   in   the   3’   untranslated   region   of SPI1 with systemic lupus erythematosus.
Arthritis Rheum 2011;63:755-763.
4) Ohashi J, Naka I, Tsuchiya N. The impact of natural selection on an ABCC11 SNP
determining earwax type. Mol Biol Evol 2011;28:849-857.
5) Chei CL, Yamagishi K, Kitamura A, Kiyama M, Imano H, Ohira T, et al. C-reactive protein
levels and risk of stroke and its subtype in Japanese: the Circulatory Risk in Communities
Study (CIRCS). Atherosclerosis 2011;217:187-193.
6) Ito I, Kawaguchi K, Kawasaki A, Hasegawa M, Ohashi J, Kawamoto M, Fujimoto M,
Takehara K, Sato S, Hara M, Tsuchiya N. Association of the FAM167A-BLK region withsystemic sclerosis. Arthritis Rheum 2010;62:890-895.

17

University of Tsukuba

Research Field: Occupational Psychiatry / Space Medicine #1
Longevity medicine Endowed Chair #2
Principal Investigator: Prof. Ichiyo Matsuzaki #1
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 of Japanese 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. Journal of 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 Japanesecedar pollinosis in recent urban areas. Arch Complex Environ Studies Arch. Com. Eff.
Study, 15,20-25,2003

18

University of Tsukuba

Radiation Biology
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
Assistant Professor Takashi Moritake:moritake@pmrc.tsukuba.ac.jp
Major Scientific Interest of the Group:
Radiation biology is a field of medical sciences dealing with research on the biologicalactions of ionizing radiation on life or living things. In this field, it is essential to establish
robust methods to evaluate and measure biological phenomena by physical parameters.
The mission of this group is to clarify the biological characteristics of x-rays and proton
beams and to improve the safety and efficacy of x-rays and proton beam radiotherapy.
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Program

1) Proton beam induced DNA damage and repair,2) Radiation induced tumor immunological reactions,3) Biological effects of x-ray micro beams,4) Radiation protection.
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) Zhengshan Hong, Yuki Kase, Takashi Moritake, Ariungerel Gerelchuluun, Lue Sun, Kenshi Suzuki,
Toshiyuki Terunuma, Kiyoshi Yasuoka, Hiroaki Kumada, Kazunori, Hideyuki Sakurai, Takeji Sakae,
and Koji Tsuboi. Lineal energy-based evaluation of oxidative DNA damage induced by proton beams
and X-rays. Int. J. Radiat. Biol. in press.

2) 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.
3) Mizumoto M, Tsuboi K, Igaki H, Yamamoto T, Takano S, Oshiro Y, Hayashi Y,
Hashii H, Kanemoto A, Nakayama H, Sugahara S, Sakurai H, Matsumura A,
Tokuuye K. Phase I/II Trial of Hyperfractionated Concomitant Boost Proton
Radiotherapy for Supratentorial Glioblastoma Multiforme. Int J Radiat Oncol Biol
Phys. 2009 Aug 19.
4) Tsuboi K, Moritake T, Tsuchida Y, Tokuuye K, Matsumura A, Ando K. Cell cycle
checkpoint and apoptosis induction in glioblastoma cells and fibroblasts irradiatedwith carbon beam. J Radiat Res (Tokyo). 2007 Jul;48(4):317-25.

19

Cooperative Graduate Programs

Research Field: Functional Genomics
Principal Investigator: Prof. Shunsuke Ishii
E-mail address: sishii@rtc.riken.jp
URL: http://rtcweb.rtc.riken.jp/lab/mg/en/mg.html
Other Faculty Member
Associate Professor Teruaki Nomura: tnomura@rtc.riken.jp
Major Scientific Interests of the Group
Transcriptional control is a key step for development, stress response, and various diseases inhuman beings. We focus on understanding the molecular mechanisms of transcription control.
Our lab has three groups (molecular biology, mouse, and Drosophila), which are using different
methods, but focus on the same transcriptional regulators.
Projects  for  Regular  Students  in  Doctoral  or  Master’s  Programs
1) Role of nuclear oncogene products Myb and Ski in cancer2) Epigenetic regulation by ATF-2 family transcription factors
3) Mechanism of iPSC generation
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) Seong KH, Li D, Shimizu H, Nakamura R and Ishii S. Inheritance of stress-induced,
ATF-2-dependent epigenetic change. Cell in press, 2011.
2) 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.
3) Yamauchi T, Ishidao T, Nomura T, Shinagawa T, Tanaka Y, Yonemura S and Ishii S. A
B-Myb complex containing clathrin and filamin is required for mitotic spindle function.
EMBO J. 27: 1852-1862, 2008.
4) Jin W, Takagi T, Kanesashi S, Kurahashi T, Nomura T, Harada J and Ishii S. Schnurri-2
controls BMP-dependent adipogenesis via interaction with Smad proteins. Dev. Cell 10:
461-471, 2006.5) Kanei-Ishii C, Ninomiya-Tsuji J, Tanikawa J, Nomura T, Ishitani T, Kishida
S, Kokura K, Kurahashi T, Ichikawa-Iwata E, Kim Y, Matsumoto K and Ishii S. Wnt-1 signal
induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK.
Genes Dev. 18, 816-829, 2004.

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Cooperative Graduate Programs

Research Field: International Medicine
Principal Investigator: Prof. Shigeyuki Kano
E-mail address: kano@ri.ncgm.go.jp
URL: http://www.ncgm.go.jp/rese/top/j/rese_trop.html
Other Faculty Members: none
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) 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, 2012
2) Tangpukdee N, Krudsood S, Kano S, Wilairatana P: Falciparum malaria parasitemia index
for predicting severe malaria. Int J Lab Hematol 34(3): 320-327, 20123) Culleton R, Coban C, Zeyrek FY, Cravo P, Kaneko A, Randrianarivelojosia M,
Andrianaranjaka V, Kano S, Farnert A, Arez AP, Sharp PM, Carter R, Tanabe K: The origins
of African Plasmodium vivax; Insights from mitochondrial genpme sequencing. PLoS ONE
6(12): e29137, 20114) Noriyuki Okudaira, Motohito Goto, Rieko Yanobu-Takanashi, Masato Tamura, Akihiro An,
Yukiko Abe, Shigeyuki Kano, Shotaro Hagiwara, Yukihito Ishizaka, Tadashi Okamura:
Involvement of Retrotransposition of Long Interspersed Nucleotide Element-1 in
DMBA/TPA-induced Skin Tumorigenesis. Cancer Science 102(11): 2000-2006, 201121

Cooperative Graduate Programs

Reserch Field: Virology
Principal Investigator: Prof. Ichiro KuraneE-mail address: kurane@nih.go.jp
URL: http://www.nih.go.jp/niid/index.html
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 thecommon 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
the Japanese encephalitis virus E protein (S123R) increases its growth rate in mouseneuroblastoma 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 and FcgammaR-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. andTakasaki, T.: Chikungunya virus isolated from a returnee to Japan from Sri Lanka: isolationof two sub-strains with different 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
antibody-dependent enhancement assay for dengue virus using stable BHK-21 cell lines
expressing Fc gammaRIIA. Journal of Virological Methods 163(2)205-9, 2010.

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Cooperative Graduate Programs

Research Field: Experimental Hematology
Principal Investigator: Prof. Yukio Nakamura
E-mail address: yukionak@brc.riken.jp
URL: 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
cell sources such as hematopoietic stem cells, ES cells and iPS cells. In addition, we are
studying the mechanisms of enucleation of RBC progenitor cells so as to improve theefficiency 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) Nakamura, Y. ES cell-derived erythroid cell lines able to produce mature red blood cells.
InTech   “Embryonic   Stem   Cells-Recent Advances in Pluripotent Stem Cell-BasedRegenerative  Medicine”  (edited  by  Craig  Atwood), Chapter 15, p273-288 (2011)2) Sudo, K., Yasuda, J., and Nakamura, Y. Gene expression profiles of cryopreserved CD34+
human umbilical cord blood cells are related to their bone marrow reconstitution abilities inmouse xenografts. Biochem. Biophys. Res. Commun. 397: 697-705 (2010)
3) Ishigaki, T., Sudo, K., Hiroyama, T., Miharada, K., Ninomiya, H., Chiba, S., Nagasawa, T.,
and Nakamura, Y. Human hematopoietic stem cells can survive in vitro for several months.
Adv. Hematol. 2009: ID936761 (open access journal) (2009)
4) Hiroyama, T., Miharada, K., Sudo, K., Danjo, I., Aoki, N., and Nakamura, Y. Establishmentof mouse embryonic stem cell-derived erythroid progenitor cell lines able to producefunctional red blood cells. PLoS ONE 3: e1544 (open access journal) (2008)
5) Miharada, K., Hiroyama, T., Sudo, K., Nagasawa, T., and Nakamura, Y. Efficientenucleation of erythroblasts differentiated in vitro from hematopoietic stem and progenitor
cells. Nat. Biotechnol. 24: 1255-1256 (2006)23

Cooperative Graduate Programs

Name of the Field: Biochemistry and Molecular Cell Biology
Principal Investigator: Professor and Director General
Keiji Tanaka
E-mail address: tanaka-kj@igakuken.or.jp
URL: http://www.igakuken.or.jp/
Other Faculty Members: Project leader, Masaaki Komatsu;
Chief Researcher, Noriyuki Matsuda; Chief Researcher,
Yasushi Saeki; Senior Researcher, Yoko Kimura; SeniorResearcher, Yukiko Yoshida
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) 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
2) Murata, S., Yashiroda, H., and Tanaka, K. (2009) Molecular mechanisms of proteasome
assembly. Nat. Rev. Mol. Cell. Biol. 10, 104-115
3) Kimura, Y., Yashiroda, H., Kudo, T., Koitabashi, S., Murata, S., Kakizuka, A., and Tanaka,
K. (2009) An inhibitor of deubiquitinating enzyme regulates ubiquitin homeostasis. Cell 137,
549-559
4) 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
5) 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
6) Komatsu, M., Waguri, S., Koike, M., Sou, Y., Ueno, T., Hara, T., Mizushima, N., Iwata, J.,
Ezaki, J., Murata, S., Hamazaki, J., Nishito, Y., Iemura, S., Natsume, N., Yanagawa, T.,
Uwayama, J., Warabi, E., Yoshida, H., Ishii, T., Kobayashi, A., Yamamoto, M., Yue, Z.,
Uchiyama, Y., Kominami, E., and Tanaka, K. (2007) Homeostatic levels of p62 control
cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149-1163
7) 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 systemcauses neurodegeneration. Nature 441, 880-884

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