Research Activities

Research Activities

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Principal Investigators

Dept. of Life Science Frontiers 
Yoshiya Kawaguchi (Professor)

Publications

Tsujimoto H, Katagiri N, Ijiri Y, Sasaki B, Kobayashi Y, Mima A, Ryosaka M, Furuyama K, Kawaguchi Y, Osafune K

In vitro methods to ensure absence of residual undifferentiated human induced pluripotent stem cells intermingled in induced nephron progenitor cells PLoS One 2022 Nov 15;17(11):e0275600

van Gurp L, Fodoulian L, Oropeza D, Furuyama K, Bru-Tari E, Vu AN, Kaddis JS, Rodríguez I, Thorel F, Herrera PL.

Generation of human islet cell type-specific identity genesets Nature Communications 2022 Apr 19;13(1)

Masui T, Nagai K, Anazawa T, Sato A, Uchida Y, Nakano K, Yogo A, Kaneda A, Nakamura N, Yoshimura M, Mizowaki T, Uza N, Fukuda A, Matsumoto S, Kanai M, Isoda H, Mizumoto M, Seo S, Hata K, Taura K, Kawaguchi Y, Takaori K, Uemoto S, Hatano E

Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution BMC Cancer. 2022 Jan 22(1):119

Nao Sankoda, Wataru Tanabe, Akito Tanaka, Hirofumi Shibata, Knut Woltjen, Tsutomu Chiba, Hironori Haga, Yoshiharu Sakai, Masaki Mandai, Takuya Yamamoto, Yasuhiro Yamada, Shinji Uemoto, Yoshiya Kawaguchi

Epithelial expression of Gata4 and Sox2 regulates specification of the squamous-columnar junction via MAPK/ERK signaling in mice Nat Commun. 2021 Jan 25;12(1):560.

Nakano K, Masui T, Yogo A, Uchida Y, Sato A, Kasai Y, Nagai K, Anazawa T, Kawaguchi Y, Uemoto S.

Chloroquine Induces Apoptosis in Pancreatic Neuroendocrine Neoplasms via Endoplasmic Reticulum Stress Endocr Relat Cancer. 2020 Jul;27(7):431-439.

Masui T, Nagai K, Anazawa T, Kasai Y, Sato A, Nakano K, Uchida Y, Yogo A, Kawaguchi Y, Takaori K, Uemoto S.

Risk factors for short recurrence-free survival after resection of pancreatic neuroendocrine tumor (PanNET) liver metastases: which patients should undergo resection? Scand J Gastroenterol. 2020 Mar 30:1-6.

Sasaki B, Uemoto S, Kawaguchi Y.

Transient FOXO1 inhibition in pancreatic endoderm promotes the generation of NGN3+ endocrine precursors from human iPSCs Stem Cell Research. 2020 Mar 6;44:101754.

Horiguchi M, Yoshida M, Hirata K, Furuyama K, Masui T, Uemoto S, Kawaguchi Y.

Senescence caused by inactivation of the homeodomain transcription factor Pdx1 in adult pancreatic acinar cells in mice. FEBS Lett. 2019 Aug;593(16):2226-2234.

Masui T, Sato A, Nakano K, Uchida Y, Yogo A, Anazawa T, Nagai K, Kawaguchi Y, Takaori K, Uemoto S.

Predictive value of the Ki67 index for lymph node metastasis of small non-functioning pancreatic neuroendocrine neoplasms. Surg Today. 2019 Jul;49(7):593-600.

Nakano K, Masui T, Yogo A, Uchida Y, Nagai K, Anazawa T, Takaori K, Kawaguchi Y, Uemoto S.

Autophagy Inhibition on In Vitro and In Vivo PanNET Models PANCREAS. 2019 Feb;48(3):446-447

Hirata K, Kodama S, Nakano Y, Minaki-Nakagawa Y, Aoyama Y, Sakikubo M, Goto T, Yoshida M,
Masui T, Yamamoto T, Uemoto S, Kawaguchi Y.

Exocrine tissue-driven TFF2 prevents apoptotic cell death of endocrine lineage during pancreas organogenesis. Sci Rep. 2019 Feb 7;9(1):1636.

Sakikubo M, Furuyama K, Horiguchi M, Hosokawa S, Aoyama Y, Tsuboi K, Goto T, Hirata K, Masui T, Dor Y, Fujiyama T, Hoshino M, Uemoto S, Kawaguchi Y.

Ptf1a inactivation in adult pancreatic acinar cells causes apoptosis through activation of the endoplasmic reticulum stress pathway. Sci Rep. 2018 Oct 25;8(1):15812.

Fujiyama T, Miyashita S, Tsuneoka Y, Kanemaru K, Kakizaki M, Kanno S, Ishikawa Y, Yamashita M, Owa T, Nagaoka M, Kawaguchi Y, Yanagawa Y, Magnuson MA, Muratani M, Shibuya A, Nabeshima YI, Yanagisawa M, Funato H, Hoshino M.

Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain. Cell Rep. 2018 Jul 3;24(1):79-94.

Shibata H, Komura S, Yamada Y, Sankoda N, Tanaka A, Ukai T, Kabata M, Sakurai S, Kuze B, Woltjen K, Haga H, Ito Y, Kawaguchi Y, Yamamoto T, Yamada Y.

In vivo reprogramming drives Kras-induced cancer development Nat Commun. 2018 May 25;9(1):2081.

Masui T, Sato A, Nakano K, Uchida Y, Yogo A, Anazawa T, Nagai K, Kawaguchi Y, Takaori K, Uemoto S.

Comparison of Recurrence Between Pancreatic and Duodenal Neuroendocrine Neoplasms After Curative Resection: A Single-Institution Analysis. Ann Surg Oncol. 2018 Feb;25(2):528-534.

Masui T, Takaori K, Anazawa T, Sato A, Nakano K, Uchida Y, Yogo A, Goto Y, Matsumoto S,
Kodama Y, Kanai M, Isoda H, Mizumoto M, Kawaguchi Y, Shibuya K, Itasaka S, Uemoto S.

A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement. Anticancer Res. 2017 Dec;37(12):7023-7030.

Sato A, Masui T, Sankoda N, Nakano K, Uchida Y, Anazawa T, Takaori K, Kawaguchi Y, Uemoto S.

A case of successful conversion from everolimus to surgical resection of a giant pancreatic neuroendocrine tumor Surg Case Rep. 2017 Dec;3(1):82.

Sato A, Masui T, Nakano K, Sankoda N, Anazawa T, Takaori K, Kawaguchi Y, Uemoto S.

Abdominal contamination with Candida albicans after pancreaticoduodenectomy is related to hemorrhage associated with pancreatic fistulas. Pancreatology. (3):484-489, 2017

Goto T, Elbahrawy A, Furuyama K, Horiguchi M, Hosokawa , Aoyama Y, Tsuboi K, Sakikubo M, Hirata K, Masui T, Kubo H, Sakai Y, Uemoto S, Kawaguchi Y.

Liver-specific Prox1 inactivation causes hepatic injury and glucose intolerance in mice. FEBS Lett. ;591(4):624-635, 2017

Masui T, Doi R, Kawaguchi Y, Sato A, Nakano K, Ito T, Anazawa T, Takaori K, Uemoto S.

Concurrent gemcitabine+S-1 neoadjuvant chemotherapy contributes to the improved survival of patients with small borderline-resectable pancreatic cancer tumors. Surg Today. ;46(11):1282-9, 2016

Kiyoto Nishi, Yuichi Sato, Mikiko Ohno, Yoshinori Hiraoka, Sayaka Saijo, Jiro Sakamoto, Po-Min Chen, Yusuke Morita, Shintaro Matsuda, Kanako Iwasaki, Kazu Sugizaki, Norio Harada, Yoshiko Mukumoto, Hiroshi Kiyonari, Kenichiro Furuyama, Yoshiya Kawaguchi, Shinji Uemoto, Toru Kita, Nobuya Inagaki, Takeshi Kimura and Eiichiro Nishi.

Nardilysin Is Required for Maintaining Pancreatic β-Cell Function. Diabetes. ;65(10):3015-27, 2016

Nakano Y, Negishi N, Gocho S, Mine T, Sakurai Y, Yazawa M, Abe K, Yagita H, Habu S, Kageyama R, Kawaguchi Y, Hozumi K

Disappearance of centroacinar cells in the Notch ligand-deficient pancreas. Gens to Cells, 20(6):500-11, 2015

Shinichi Hosokawa, Kenichiro Furuyama, Masashi Horiguchi, Yoshiki Aoyama, Kunihiko Tsuboi, Morito Sakikubo, Toshihiko Goto, Koji Hirata, Wataru Tanabe, Yasuhiro Nakano, Haruhiko Akiyama, Ryoichiro Kageyama, Shinji Uemoto, Yoshiya Kawaguchi

Impact of Sox9 Dosage and Hes1-mediated Notch Signaling in Controlling the Plasticity of Adult Pancreatic Duct Cells in Mice. Scientific Reports 5, Article number: 8518, 2015

Kawaguchi Y*

Sox9 and reprogramming of liver and pancreatic progenitors. J Clin Invest. 123(5):1881-1886, 2013

Nakanishi Y, Seno H, Fukuoka A, Ueo T, Yamaga Y, Maruno T, Nakanishi N, Kanda K, Komekado H, Kawada M, Isomura A,Kawada K, Sakai Y, Yanagita M, Kageyama R, Kawaguchi Y, Taketo MM, Yonehara S, Chiba T.

Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat Genet. 45(1):98-103, 2013

Furuyama K, Kawaguchi Y*, Akiyama H*, Horiguchi M, Kodama S, Kuhara T, Hosokawa S, Elbahrawy A, Soeda T, Koizumi M, Masui T, Kawaguchi M, Takaori K, Doi R, Nishi E, Kakinoki R, Deng JM, Behringer RR, Nakamura T, Uemoto S

Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine Nat Genet. 43(1):34-41, 2011

Kawaguchi Y*, Takaori K, Uemoto S

Genetic lineage tracing, a powerful tool to investigate the embryonic organogenesis and adult organ maintenance of the pancreas J Hepatobiliary Pancreat Sci. 18(1):1-5, 2011

Nishda K, Hoshino M, Kawaguchi Y, Murakami F

Ptf1a directly controls expression of immunoglobulin superfamily molecules Nephrin and Neph3 in the developing central nervous system J Biol Chem. 285;373-80, 2010

Betley JN, Wright CVE, Kawaguchi Y, Erdelyi F, Szabo G, Jessell TM, Kaltschmidt JA

Stringent specificity in the construction of a GABAergic presynaptic inhibitory circuit Cell. 139(1): 161-74, 2009

Fujiyama T, Yamada M, Terao M, Terashima T, Hioki H, Inoue YU, Inoue T, Masuyama N, Obata K, Yanagawa Y, Kawaguchi Y, Nabeshima Y, Hoshino M

Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1. Development. 136(12):2049-58, 2009

Obata K, Hirono M, Kume N, Kawaguchi Y, Itohara S and Yanagawa Y

GABA and synaptic inhibition of mouse cerebellum lacking glutamate decarboxylase 67. Biochem Biophys Res Commun. ;670(3) :429-33. 2008

Fukuda A, Kawaguchi Y*, Furuyama K, Kodama S, Horiguchi M, Kuhara T, Kawaguchi M, Terao M, Doi R, Wright CV, Hoshino M, Chiba T, Uemoto S

Reduction of Ptf1a gene dosage causes pancreatic hypoplasia and diabetes in mice Diabetes. 57 (9) : 2421-2431, 2008

Morton JP, Mongeau ME, Klimstra DS, Morris JP, Lee YC, Kawaguchi Y, Wright CV, Hebrok M and Lewis BC

Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis. Proc Natl Acad Sci U S A. 20;104(12):5103-8. 2007

Fujikura J, Hosoda K, Kawaguchi Y, Noguchi M, Iwakura H, Odori S, Mori E, Tomita T, Hirata M Ebihara K, Masuzaki H, Fukuda A, Furuyama K, Tanigaki K, Yabe D and Nakao K

Rbp-j regulates expansion of pancreatic epithelial cells and their differentiation into exocrine cells during mouse development. Dev Dyn.;236(10):2779-91. 2007

YamadaM, Terao M, Terashima T, Fujiyama T, Kawaguchi Y, Nabeshima Y and Hoshino M

Origin of climbing fiber neurons and their developmental dependence on Ptf1a. J Neurosci. 27(41):10924-34. 2007

Fujitani Y, Fuijtani S, Boyer DF, Gannon M, Kawaguchi Y, Ray M, Shiota M, Stein RW, Magnuson MA and Wright CV

Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation Genes Dev.;20(2):253-66. 2006

Fukuda A, Kawaguchi Y*, Furuyama K, Kodama S, Kuhara T, Horiguchi M, Koizumi M, Fujimoto K, Doi R, Wright CVE, Chiba T

Loss of the major duodenal papilla results in brown pigment biliary stone formation in pdx1 null mice Gastroenterology.;130(3):855-67. 2006

Fukuda A, Kawaguchi Y*, Furuyama K, Kodama S, Horiguchi M, Kuhara T, Koizumi M, Boyer DF., Fujimoto K, Doi R, Kageyama R, Wright CVE, Chiba T

Ectopic pancreas formation in Hes1 -knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas. J Clin Invest.;116(6):1484-93. 2006

Miyatsuka T, Kaneto H, Shiraiwa T, Matsuoka TA, Yamamoto K, Kato K, Nakamura Y, Akira S, Takeda K, Kajimoto Y, Yamasaki Y, Sandgren EP, Kawaguchi Y, Wright CV and Fujitani Y

Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation. Genes Dev.;20(11):1435-40.2006

Koizumi M, Nagai K, Kida A, Kami K, Ito D, Fujimoto K, Kawaguchi Y and Doi R

Forced expression of PDX-1 induces insulin production in intestinal epithelia. Surgery.;140:273-80. 2006

Fujitani Y, Fujitani S, Luo H, Qui F, Burlison J Long Q, Kawaguchi Y, Edlund H, MacDonald RJ, Furukawa T, Fujikado T, Magunuson MA, Xiang M and Wright CV

Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Development.;133(22):4439-50. 2006

Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura YV, Fukuda A, Fuse T, Matsuo N, Sone M, Watanabe M, Bito H, Terashima T, Wright CV, Kawaguchi Y, Nakao K and Nabeshima Y

Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron.;47(2):201-13. 2005

Koizumi M, Doi R, Fujimoto K, Ito D, Toyoda E, Mori T, Kami K, Kawaguchi Y, Gittes GK and Imamura M

Pancreatic epithelial cells can be converted into insulin-producing cells by GLP-1 in conjunction with virus-mediated gene transfer of pdx-1. Surgery.;138:125-33. 2005

Nakajima S, Doi R, Toyoda E, Tsuji S, Wada M, Koizumi M, Tulachan S.S, Ito D, Kami K, Mori T, Kawaguchi Y, Fujimoto K, Hosotani R, and Imamura M

N-Cadherin Expression and Epithelial-Mesenchymal Transition in Pancreatic Carcinoma Clinical Caner Research 10: 4125-33, 2004

Koizumi M , Doi R, Toyoda E, Tulachan S.S, Kami K, Mori T, Ito D, Kawaguchi Y, Fujimoto K, Gittes G.K and Imamura M

Hepatic regeneration and enforced PDX-1 expression accelerate transdifferentiation in liver Surgery 136: 449-57, 2004

Tulachan S.S., Doi, R, Kawaguchi Y, Tsuji S, Nakajima S, Masui T, Koizumi M, Toyoda E, Mori T, Ito D, Kami K, Fujimoto K and Imamura M

All-Trans Retinoic Acid Induces Differentiation of Ducts and Endocrine Cells by Mesenchymal/Epithelial Interactions in Embryonic Pancreas Diabetes 52: 76-84, 2003

Hingorani S.R., Petricoin III E.F., Maitra A, Rajapakse V., King C., Jacobetz M. A., Ross S., Conrads T. P., Veenstra T. D., Hitt B. A., Kawaguchi Y., Johann D., Liotta L.A., Crawford H. C., Putt M. E., Jacks T., Wright C.V.E., Hruban R.H., Lowy A.M and Tuveson D.A

Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse Cancer Cell 4:437-49, 2003

Koizumi M, Doi R, Toyoda E, Masui T, Tulachan SS, Kawaguchi Y, Fujimoto K, Gittes GK, Imamura M

Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer. Surgery. 134:260-6, 2003

Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald R. J and Wright C.V.E

The role of transcriptional regulator ptf1a in converting intestinal to pancreatic progenitors Nat.Genet. 32(1): 128-134, 2002

Kawaguchi Y*, Takebayashi H, Kakizuka A, Arii S, Kato M and Imamura M

Expression of Fas-estrogen receptor fusion protein induces cell deathin pancreatic cancer cell lines Cancer Lett. 116(1): 53-59, 1997

Nakamoto M, Takebayashi H, Kawaguchi Y, Nakamura S, Taniwaki M, Nakamura Y, Ishikawa Y, Akiguchi I, Kimura J and Kakizuka A

A CAG/CTG expansion in the normal population Nat. Genet. 17(4): 385-386, 1997

Okada N, Kubota A, Imamura T, Suwa H, Kawaguchi Y, Ohshio G, Seino Y, Imamura M

Evaluation of cholecystokinin, gastrin, CCK-A receptor, and CCK-B/gastrin receptor gene expressions in gastric cancer. Cancer Lett. 1996 Sep 10;106(2):257-62.

Maruyama H, Nakamura S, Matusyama Z, Sakai T, Doyu M, Sobue G, Tsujibata M, Oh-I T, Nishino T, Sunahara N, Takahashi R, Hayashi M, Nishino I, Ohtake T, Oda T, Nishimura M, Saida T, Matsumoto H, Baba M, Kawaguchi Y, Kakizuka A and Kawakami H

Molecular features of the CAG repeats and clinical manifestations of Machado-Joseph disease Hum. Mol. Genet. 4: 807-812, 1995

Kawakami H, Maruyama H, Nakamura S, Kawaguchi Y, Kakizuka A, Doyu M and Sobue G

Unique features of the CAG repeats in Machado-Joseph disease Nat.Genet. 9(4): 344-345, 1995

Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, Kimura J, Narumiya S and Kakizuka A

CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1 Nat. Genet. 8(3): 221-228, 1994

Kawaguchi Y, Hoshimaru M, Nawa H and Nakanishi S

Sequence analysis of cloned cDNA for rat substance P precursor; existence of a third substance P precursor Biochem Biophys Res Commun 139(3): 1040-1046, 1986
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