Place of Birth: Saga, Japan

CURRICULUM VITAE

Name: Akihiko Yoshimura

Date of Birth: 12/12/58

Place of Birth: Saga, Japan

Education:

Undergraduate: 1976-1980 Kyoto University, Kyoto, Japan

Biology and Chemistry B.S. awarded 3/80

Graduate: 1980-1985 Kyoto University, Kyoto, Japan

Department of Biophysics Ph.D. awarded 3/86

Research Appointment:

1985-1987 Assistant Professor Oita Medical School, Oita, Japan

1987-1989 Assistant Professor Cancer Research Institute

Kagoshima University, Kagoshima, Japan

1989-1991 Postdoctoral Research Fellow

Whitehead Institute for Biomedical Research, MIT Cambridge, MA, USA

1989-1995 Associate Professor, Kagoshima University, Kagoshima, Japan

1995-2000 Professor, Insutitute of Life Science, Kurume University

Kurume, Japan

2001-2008 Professor, Medical Institute of Bioregulation,

Kyushu University Fukuoka, Japan

2008- present Professor, Department of Microbiology and Immunology,

Keio University of Medicine

Award

Japan Biochemistry Society Award 1998

Japan Immunology Society Award 2001

Mochida Memorial Award 2007

Kakiuchi Samuro Award (Japan Biochemical Society) 2007

Major publications

Ichiyama K, Sekiya T, Inoue N, Tamiya T, Kashiwagi I, Kimura A, Morita R, Muto G, Shichita T, Takahashi R, Yoshimura A.

Transcription Factor Smad-Independent T Helper 17 Cell Induction by Transforming-Growth Factor-β Is Mediated by Suppression of Eomesodermin.

Immunity. 2011 May 27;34(5):741-54.

Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Klöppel G, Yoshimura A, Reindl W, Sipos B, Akira S, Schmid RM, Algül H.

Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer.

Cancer Cell. 2011 Apr 12;19(4):456-69.

Sekiya T, Kashiwagi I, Inoue N, Morita R, Hori S, Waldmann H, Rudensky AY, Ichinose H, Metzger D, Chambon P, Yoshimura A.

The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells.

Nature Commun. 2011;2:269.

Chinen T, Komai K, Muto G,Morita R, Inoue N, Yoshida H, Sekiya T, Yoshida R, Nakamura K, Takayanagi R,Yoshimura A; Prostaglandin E2 and SOCS1have a role in intestinal immune tolerance. Nature Commun2,E190, 2011 doi:10.1038/ncomms1181

Tanaka KA, Suzuki KG, Shirai YM, Shibutani ST, Miyahara MS, Tsuboi H, Yahara M, Yoshimura A, Mayor S, Fujiwara TK, Kusumi A. Membrane molecules mobile even after chemical fixation.Nature Methods. 2010 Nov;7(11):865-6. Epub 2010 Oct 3. doi:10.1038/nmeth.f.314

Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, Hanada T, Yoshimura A, Baltimore D, Rudensky AY. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses.Cell. 2010 Sep 17;142(6):914-29. doi:10.1016/j.cell.2010.08.012

Takimoto T, Wakabayashi Y, Sekiya T, Inoue N, Morita R, Ichiyama K, Takahashi R, Asakawa M, Muto G, Mori T, Hasegawa E, Shizuya S, Hara T, Nomura M, Yoshimura A. Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development.J Immunol. 2010 Jul 15;185(2):842-55. Epub 2010 Jun 14. doi: 10.4049/ jimmunol.0904100

Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R,.Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E. Clinical and mutational spectrum of Legius syndrome JAMA 2009 Nov 18;302(19):2111-8.

Taleb S, Romain M, Ramkhelawon B, Uyttenhove C, Pasterkamp G, Herbin O, Esposito B, Perez N, Yasukawa H, Van Snick J, Yoshimura A, Tedgui A, Mallat Z. Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J Exp Med. 2009 Sep 28;206(10):2067-77.

Shichita T, Sugiyama Y, Ooboshi H, Sugimori H, Nakagawa R, Takada I, Iwaki T, Okada Y, Iida M, Cua DJ, Iwakura Y, Yoshimura A. Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury. Nat Med. 2009 Aug;15(8):946-50.

Koga K, Takaesu G, Yoshida R, Nakaya M, Kobayashi T, Kinjyo I, Yoshimura A. Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the c-Fos protein phosphorylated by IKKbeta Immunity 2009 30(3): 372-383

Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K, Rudensky AY. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein.Immunity. 2009 Jan;30(1):80-91.

Le Y, Zhu BM, Harley B, Park SY, Kobayashi T, Manis JP, Luo HR, Yoshimura A, Hennighausen L, Silberstein LE. SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis. Immunity. 2007 Nov;27(5):811-23.

Brems H, Chmara M, Sahbatou, Denayer, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E. Germline loss-of-function mutations in SPRED1 cause a NF1-like phenotype. Nature Genet. 2007 Sep;39(9):1120-6.

Yoshimura A., Naka, T., Kubo, M., SOCS proteins, cytokine signalling and immune regulation.

Nature Review Immunology. 2007 Jun;7(6):454-65.

Taniguchi K, Kohno RI, Ayada T, Kato R, Ichiyama K, Morisada T, Oike Y, Yonemitsu Y, Maehara Y, Yoshimura A. Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor-3 signaling.Mol Cell Biol. 2007 Jun;27(12):4541-50

Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM, Villarino AV, Huang Q, Yoshimura A, Sehy D, Saris CJ, O'Shea JJ, Hennighausen L, Ernst M, Hunter CA. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nature Immunol. 2006 Sep;7(9):937-45.

Kievit P, Howard JK, Badman MK, Balthasar N, Coppari R, Mori H, Lee CE, Elmquist JK, Yoshimura A, Flier JS. Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells. Cell Metab. 2006 Aug;4(2):123-32

Ogata H, Kobayashi T, Chinen T, Takaki H, Sanada T, Minoda Y, Koga K, Takaesu G, Maehara Y, Iida M, Yoshimura A. Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induced hepatocarcinogenesis. Gastroenterology. 2006 Jul;131(1):179-93.

Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, Yamane J, Yoshimura A, Iwamoto Y, Toyama Y, Okano H. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nature Med. 2006 Jul;12(7):829-34.

Hanada T, Kobayashi T, Chinen T, Saeki K, Takaki H, Koga K, Minoda Y, Sanada T, Yoshioka T, Mimata H, Kato S, Yoshimura A.IFNgamma-dependent, spontaneous development of colorectal carcinomas in SOCS1-deficient mice. J Exp Med. 2006 Jun 12;203(6):1391-7.

Kinjyo I, Inoue H, Hamano S, Fukuyama S, Yoshimura T, Koga K, Takaki H, Himeno K, Takaesu G, Kobayashi T, Yoshimura A. Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1. J Exp Med. 2006 Apr 17;203(4):1021-31.

Chen Z, Laurence A, Kanno Y, Pacher-Zavisin M, Zhu BM, Tato C, Yoshimura A, Hennighausen L, O'Shea JJ. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells.Proc Natl Acad Sci U S A.2006 May 23;103(21):8137-42.

Chinen T, Kobayashi T, Ogata H, Takaesu G, Takaki H, Hashimoto M, Yagita H, Nawata H, Yoshimura A. Suppressor of Cytokine Signaling-1 Regulates Inflammatory Bowel Disease in Which Both IFNgamma and IL-4 Are Involved. Gastroenterology. 2006;130: 373-388.

Kobayashi T, Takaesu G, Yoshimura A. Mal-function of TLRs by SOCS. Nature Immunol. 2006 ;7:123-124.

Moriyama M, Sato T, Inoue H, Fukuyama S, Teranishi H, Kangawa K, Kano T, Yoshimura A, Kojima M. The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells. J Exp Med. 2005;202: 217-224.

Taketomi T, Yoshiga D, Taniguchi K, Kobayashi T, Nonami A, Kato R, Sasaki M, Sasaki A, Ishibashi H, Moriyama M, Nakamura KI, Nishimura J, Yoshimura A. Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia. Nature Neurosci. 2005 8, 855-857

Inoue H, Kato R, Fukuyama S, Nonami A, Taniguchi K, Matsumoto K, Nakano T, Tsuda M, Matsumura M, Kubo M, Ishikawa F, Moon BG, Takatsu K, Nakanishi Y, Yoshimura A. Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness. J Exp Med.;201:73-82, 2005.

Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H, and Yoshimura A SOCS3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nature Mediciene 10: 739-743, 2004

Yoshida T, Ogata H, Kamio M, Joo A, Shiraishi H, Tokunaga Y, Sata M, Nagai, H and Yoshimura A SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. J Exp Med. 199: 1701-1707, 2004

Murakoshi H, Iino R, Kobayashi T, Fujiwara T, Ohshima C, Yoshimura A, Kusumi A.Single-molecule imaging analysis of Ras activation in living cells. Proc Natl Acad Sci U S A. 101; 7317-7322, 2004

Nobuhisa I, Kato R, Inoue H, Takizawa M, Okita K, Yoshimura A, Taga T. Spred-2 Suppresses Aorta-Gonad-Mesonephros Hematopoiesis by Inhibiting MAP Kinase Activation. J Exp Med. 199:737-742, 2004.

Qu L, Huang S, Baltzis D, Rivas-Estilla AM, Pluquet O, Hatzoglou M, Koumenis C, Taya Y, Yoshimura A, Koromilas AE. Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3{beta} Genes Dev. 18:261-277, 2004.

Kubo M, Hanada T, Yoshimura A. Suppressors of cytokine signaling and immunity. Nature Immunol. 2003, 4: 1169-1176.

Hamano S, Himeno K, Miyazaki Y, Ishii K, Yamanaka A, Takeda A, Zhang M, Hisaeda H, Mak TW, Yoshimura A, Yoshida H. WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. Immunity. 2003, 19: 657-667.

Hanada T, Yoshida H, Kato S, Tanaka K, Masutani K, Tsukada J, Nomura Y, Mimata H, Kubo M, Yoshimura A. Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity. Immunity. 2003; 19: 437-450.

Seki Y, Inoue H, Nagata N, Hayashi K, Fukuyama S, Matsumoto K, Komine O, Hamano S, Himeno K, Inagaki-Ohara K, Cacalano N, O'Garra A, Oshida T, Saito H, Johnston JA, Yoshimura A, Kubo M.: SOCS-3 regulates onset and maintenance of TH2-mediated allergic responses Nature Medicine 2003, 9, 1047-1054

Yasukawa H, Ohishi M, Mori H, Murakami M, Chinen T, Aki D, Hanada T, Takeda K, Akira S, Hoshijima M, Hirano T, Chien KR, and Yoshimura A; IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages Nature Immunol. 2003; 4, 551-556

Saeki K, Miura Y, Aki D, Kurosaki T, and Yoshimura A; The B cell-specific major raft protein, Raftlin is necessary for the integrity of lipid raft and BCR signal transduction. EMBO J. 2003, 22:3015-3026

Sasaki,A, Taketomi T, Kato R, Saeki K, Nonami A, Sasaki M, Kuriyama M,Saito N,Shibuya M, Yoshimura A. Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1 Nature Cell Biol. 2003, 5:427-432.

Yajima T, Duplain H, Iwatate M, Kido M, Hoshijima M, Weitzman MD, Nakamura T, Woodard S, Xiong D, Yoshimura A, Chien KR, Knowlton KU. The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury. J Clin Invest. 2003, 111: 469-478.

Matsumoto A, Seki YI, Watanabe R, Hayashi K, Johnston JA, Harada Y, Abe R, Yoshimura A, Kubo M. A Role of Suppressor of Cytokine Signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated Interleukin 2 Production. J Exp Med. 2003, 197: 425-436.

Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M, Yoshida H, Kubo M, and Yoshimura A SOCS1/JAB Is a Negative Regulator of LPS-Induced Macrophage Activation. Immunity. 2002, 17: 583-591

Seki YI, Hayashi K, Matsumoto A, Seki N, Tsukada J, Ransom J, Naka T, Kishimoto T, Yoshimura A, Kubo M. Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation. Proc Natl Acad Sci U S A. 2002, 99; 13003-13008

Yoshida T, Hanada T, Tokuhisa T, Kosai K, Sata M, Kohara M, Yoshimura A. Activation of STAT3 by the Hepatitis C virus core protein leads to cellular transformation J. Exp. Med. 2002 196: 641-653.

Flodstrom M, Maday A, Balakrishna D, Cleary MM, Yoshimura A and Sarvetnick N; Antiviral defenses expressed by the pancreatic b cell govern the development of type 1 diabetes after Coxsackievirus B4 infection. Nature Immunology. 3 : 373-382, 2002.

Ohtsuka S, Takaki S, Iseki S, Miyoshi K, Nakagata N, Kataoka Y, Yoshida N, Takatsu K and Yoshimura A; SH2-B is Required for both Male and Female Reproduction. Mol Cell Biol. 22 : 3066-3077, 2002.

Wakioka T, Sasaki A, Kato R, Shouda T, Matsumoto A, Miyoshi K, Tsuneoka M, Komiya S, Baron R and Yoshimura A; Spred is a Sprouty-related suppressor of Ras signaling. Nature. 412 : 647-651, 2001.

Shouda T, Yoshida T, Hanada T, Wakioka T, Oishi M, Miyoshi K, Komiya S, Kosai K, Hanakawa Y, Hashimoto K, Nagata K and Yoshimura A; Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis J Clin Invest. 108 : 1781-1788, 2001.

Yasukawa H, Hoshijima M, Gu Y, Nakamura T, Pradervand S, Hanada T, Hanakawa Y, Yoshimura A, Ross J Jr and Chien KR; SOCS3 is a biomechanical stress inducible gene that suppresses gp130 mediated cardiac myocyte hypertrophy and survival pathways J Clin Invest. 108 : 1459-1467, 2001..

Suzuki A, Hanada T, Mitsuyama K, Yoshida T, Kamizono S, Hoshino T, Kubo M, Yamashita A, Okabe M, Takeda K, Akira S, Matsumoto S, Toyonaga A, Sata M and Yoshimura A; CIS3/SOCS3/SSI3 Plays a Negative Regulatory Role in STAT3 Activation and Intestinal Inflammation. J Exp Med. 193 : 471-482, 2001.

Yasukawa H, Sasaki A and Yoshimura A; Negative Regulation of Cytokine Signaling Pathways. Annu Rev Immunol. 18 : 143-164, 2000.

Marine J-C, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A and Ihle JN; SOCS3 Is Essential in the Regulation of Fetal Liver Erythropoiesis. Cell. 98 : 617-627, 1999.

Marine J-C, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A and Ihle JN; SOCS1 Deficiency Causes a Lymphocyte-Dependent Perinatal Lethality. Cell. 98 : 609-616, 1999.

Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka A, Imaizumi T, Matsuda T, Ihle JN and Yoshimura A; The JAK-Binding Protein JAB Inhibits Janus Tyrosine Kinase Activity Through Binding in the Activation Loop. EMBO J. 18 : 1309-1320, 1999.

Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanekura Y, Komiya S and Yoshimura A; A new protein containing an SH2 domain that inhibits JAK kinases. Nature. 387 : 921-924, 1997.

Yoshimura A, Ichihara, M., Kinjyo, I., Moriyama, M., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Hara, T., Miyajima, A. :Mouse oncostatin M: an immediate early response gene induced by multiple cytokines through the JAK/STAT5 pathway. EMBO J. 15, 1055-1063, 1996.

Yoshimura A. , Ohkubo, T., Kiguchi, T., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Hara, T., and Miyajima, A. : A novel cytokine-inducible gene CIS encodes an SH2-contanining protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors.EMBO J. 14, 2816-2826, 1995

Yoshimura A : Second subunit of EPO receptor? Nature 372, 137-138, 1994

Ohashi, H., Maruyama, K., Liu, Y. and Yoshimura A.: Ligand-induced activation of chimeric receptors between the erythropoietin receptor and receptor tyrosine kinases. Proc. Natl. Acad. Sci. USA. 91, 158-162, 1994

Yoshimura A. and Lodish, H. F.: In vitro phosphorylation of the erythropoietin receptor and an associated protein, pp130. Mol. Cell. Biol. 12, 706-715, 1992

Watowich, S. S., Yoshimura A., Longmore, G., Hilton, D. J., Yoshimura, Y., and Lodish, H. F.: Homodimerization and constitutive activation of the erythropoietin receptor. Proc. Natl. Acad. Sci. USA. 89, 2140-2144, 1992

Yoshimura A., Longmore, G. and Lodish, H. F.: Point mutation in the exoplasmic domain of the erythropoietin receptor resulting in hormone-independent activation and tumorigenecity. Nature. 348, 647-649, 1990

Yoshimura A., D'Andrea, A. D. and Lodish, H. F.: Friend spleen focus forming virus glycoprotein gp55 interacts with erythropoietin receptor in the endoplasmic reticulum and affects receptor metabolism. Proc. Natl. Acad. Sci. USA. 87, 4139-4143, 1990

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