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    Fumihiko Urano MD, PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressWashington University School of Medicine
    660 South Euclid, Campus Box 8127
    St. Louis MO 63110
    Phone314-362-8683
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentTranslational Science

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Gene Function and Expression

        Overview 
        Narrative

        Academic Background

        Fumihiko Urano received his M.D. in 1994 and his Ph.D. in Pathology in 1998 from Keio University Graduate School of Medicine in Tokyo, Japan. In 1995, he completed his residency in Pathology at Keio University Hospital in Tokyo. From 1998 to 2002, he was a post-doctoral fellow at the Skirball Institute of Biomolecular Medicine at the New York University School of Medicine, where his work was supported by research fellowships from the Japan Society for the Promotion of Science and the Uehara Memorial Foundation. Dr. Urano joined the Program in Gene Function and Expression at the University of Massachusetts Medical School as an Assistant Professor in the fall of 2002.

        Role of ER Stress in Diabetes and Aging

        Photo: Fumihiko Urano, M.D., Ph.D. The goal of our laboratory is to understand the molecular mechanisms of Endoplasmic Retiuculm stress (ER stress) diseases such as Alzheimer's disease, Parkinson's disease, Prion disease, ALS and diabetes mellitus. These most devastating human diseases are associated with pathological accumulations of abnormal proteins in cells. An overwhelming body of evidence suggests that a special type of cell stress called Endoplasmic Reticulum stress (ER stress) has an important function in the pathogenesis of such diseases. We are also studying the relationship between ER stress and Aging because accumulations of abnormal proteins may accelerate age-related cellular dysfunction.

        What is Endoplasmic Reticulum (ER)?

        Proteins are needed for the body to function properly. They are the basis of body structures and are used to synthesize enzymes and antibodies in cells. Proteins are synthesized in our cells. However, newly synthesized proteins are not functional yet. To be functional, they should mature inside of a cellular compartment called the Endoplasmic Reticulum (ER). It is like that a baby is growing in the uterus. In the lumen of the ER, proteins obtain their proper three-dimensional structure and mature to carry out their functions (i.e., become functional). This process is called protein folding. ER has an essential function in this process, especially for secreted protein and receptors such as insulin, amyloid beta and serotonin transporter. Defects of these proteins have been known to cause diabetes, Alzheimer's disease, and bipolar disorder respectively.

        What are "Endoplasmic Reticulum Stress (ER stress) Diseases"?

        Protein folding in the ER is crucial for us. However, in some instances, the sensitive environment in the ER can be perturbed by pathophysiological processes such as viral infections, environmental toxins, and mutant protein expression, as well as natural processes such as the large biosynthetic load placed on the ER. This causes the accumulation of immature and abnormal proteins in cells, leading to ER stress. Our body has an adaptive response that counteracts ER stress termed "Unfolded Protein Response (UPR)". Therefore, as long as the UPR can mitigate ER stress, our body functions properly.

        However, under some pathological circumstances, a lot of abnormal proteins accumulate, leading to a high level of ER stress. This high level of ER stress cannot be mitigated by an adaptive response (i.e., the UPR), leading to malfunction of our cells. These pathological circumstances include environmental stress, virus infection, genetic defects, and obesity. We group the human diseases that are associated with the accumulation of abnormal proteins in the ER into "ER Stress Diseases".

        ER stress and Diabetes

        Diabetes is a group of disorders defined by a state of high blood sugar caused by an absolute deficiency of insulin (type 1 diabetes) or a relative deficiency of insulin (type 2 diabetes). Secreted from pancreatic beta cells, insulin is essential to lowering blood sugar. While patients with type 2 diabetes need to take medications that stimulate insulin secretion from beta cells, patients with type 1 diabetes lack insulin-producing beta cells and need to inject themselves with synthetic insulin. We have found that a high level of ER stress has an important function in the pathogenesis of both tyep 1 and type 2 diabetes. We seek to develop new clinical approaches based on the prevention of diabetes by the development of drugs that block the ER stress-mediated cellular dysfunction.

        Figure

        Figure 1: Three types of adaptive responses to the accumulations of unfolded proteins in the ER. The ER senses the folding status of newly synthesized proteins.

        Figure 1: Three types of adaptive responses to the accumulations of unfolded proteins in the ER.
        The ER senses the folding status of newly synthesized proteins. Three types of adaptive responses are activated in response to the accumulation of unfolded proteins.

        Figure 2: Schematic representation of the role of ER stress in the pathogenesis of diabetes.

        Figure 2: Schematic representation of the role of ER stress in the pathogenesis of diabetes.

        Laboratory Personnel

        Sonya Fonseca, Graduate Student
        Rajarshi Ghosh, Graduate Student
        Shinsuke Ishigaki, Postdoctoral Fellow
        Kathryn Lipson, Postdoctoral Fellow
        Christine Oslowski, Graduate Student
        Karen Sargent, Research Assistant
        Lee Yuan, Graduate Student
        Rachel Buglione-Corbett, MD/PhD Student
        Apoorva Trivedi, Intern



        Rotation Projects

        Rotation Projects

        You can participate in numerous ongoing projects in our laboratory. The goal of our laboratory is to develop new clinical approaches for ER stress diseases such as diabetes, neurodegenerative diseases (e.g., ALS, Alzheimer's disease) and aging process.

        A. Diabetes

        Diabetes is a group of disorders defined by a state of high blood sugar caused by an absolute deficiency of insulin (type 1 diabetes) or a relative deficiency of insulin (type 2 diabetes). Secreted from pancreatic beta cells, insulin is essential to lowering blood sugar. While patients with type 2 diabetes need to take medications that stimulate insulin secretion from beta cells, patients with type 1 diabetes lack insulin-producing beta cells and need to inject themselves with synthetic insulin. Our data strongly suggest that ER stress-mediated beta-cell dysfunction and beta-cell death have important functions in the pathogenesis of both type 1 and type 2 diabetes.

        Project 1. To define the role of IRE1 signaling in pancreatic beta cells. IRE1 is an enzyme localized to the endoplasmic reticulum and a central component of the unfolded protein response (UPR) that counteracts ER stress. Our results demonstrate an important relationship between the biosynthesis of insulin and the activation of IRE1 signaling in pancreatic beta cells. We will define the function of IRE1 signaling in pancreatic beta cells using tissue culture system and mouse model. We will also develop a system to control IRE1 signaling in pancreatic beta cells using a conditionally active form of IRE1.

        Project 2. To study the molecular mechanisms of beta cell death mediated by ER stress. Our preliminary results suggest that only a slight increase in ER stress could lead to beta cell death. Using tissue culture system and mouse model, we will test if beta cells become more resistant to ER stress when we reduce the baseline level of ER stress by manipulating insulin biosynthesis.

        Project 3. To determine if synthetic peptide-based activators of IRE1 make beta cells more resistant to ER stress-mediated cell death. Our preliminary data indicate that a synthetic peptide, glucagon-like peptide 1 (GLP-1) fragment 7-37, is an activator of IRE1. Using mouse primary islets and beta-cell lines, we will test if the treatment of beta cells with GLP-1 fragment 7-37 makes beat cells more resistant to ER stress. We will also study the function of GLP-1 analog, Exendin-4, in IRE1 activation and resistance to ER stress.

        Project 4. To determine whether downstream components of IRE1, WFS1 and WIND, have important functions in protecting beta cells from ER stress-mediated cell death. We have found that WFS1 and WIND, which are downstream components of IRE1 in pancreatic beta cells, protect beta cells from ER stress-mediated apoptosis. We will study the expression levels of WFS1 and WIND in beta cell lines and mouse primary islets treated with GLP-1 and Exendin-4. We will also study the viability of WFS1-knockdown and WIND-knockdown beta cells under ER stress conditions.

        Project 5. To screen chemical compounds that activate IRE1. We will screen additional drugs that can ideally be taken orally for the activation of IRE1.

        B. Wolfram syndrome-Diabetes and Neurodegeneration

        Patients with Wolfram syndrome, a genetic disorder, develop diabetes mellitus, as well as neurodegenerative disorders such as optic atrophy, diabetes insipidus, and auditory nerve deafness. Families that exhibit Wolfram syndrome share mutations in a gene encoding WFS1 protein, a transmembrane protein localized to the endoplasmic reticulum (ER). This, at present, is the only clue to the pathogenesis of Wolfram syndrome. We and other groups have recently discovered that WFS1 has an important function in mitigating ER stress in pancreatic beta cells. Therefore, loss of function of WFS1 causes a high level of ER stress that leads to beta-cell dysfunction and death.

        Project 6. To determine the physiological mechanisms whereby WFS1 lowers ER stress levels in pancreatic beta cells. We hypothesize that WFS1 negatively regulates ER stress by protein degradation and mitigates ER stress in beta cells. We will determine the physiological mechanisms whereby WFS1 mitigates ER stress levels in pancreatic beta cells and neurons.

        Project 7. To determine whether WIND protects pancreatic beta cells from apoptosis in Wolfram syndrome. We hypothesize that WIND, a novel anti-apoptotic factor in ER stress signaling, functions in preventing ER stress-induced beta-cell death and neuronal cell death. We will study the anti-apoptotic function of WIND in beta cells and neurons.



        Bibliographic 
        selected publications
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        1. Hara T, Urano F. ER stress and ß cell death - therapeutic approach to combat ER stress. Nihon Yakurigaku Zasshi. 2014 Aug; 144(2):53-8.
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        2. Liew CW, Assmann A, Templin AT, Raum JC, Lipson KL, Rajan S, Qiang G, Hu J, Kawamori D, Lindberg I, Philipson LH, Sonenberg N, Goldfine AB, Stoffers DA, Mirmira RG, Urano F, Kulkarni RN. Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic ß cells. Proc Natl Acad Sci U S A. 2014 Jun 3; 111(22):E2319-28.
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        3. Urano F. Wolfram Syndrome iPS Cells: The First Human Cell Model of Endoplasmic Reticulum Disease. Diabetes. 2014 Mar; 63(3):844-6.
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        4. Urano F. Diabetes: Targeting endoplasmic reticulum to combat juvenile diabetes. Nat Rev Endocrinol. 2014 Mar; 10(3):129-30.
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        5. Unanue ER, Urano F. Endoplasmic reticulum: an interface between the immune system and metabolism. Diabetes. 2014 Jan; 63(1):48-9.
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        6. Jurczyk A, Diiorio P, Brostowin D, Leehy L, Yang C, Urano F, Harlan DM, Shultz LD, Greiner DL, Bortell R. Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2r?(null) mice treated with alogliptin. Diabetes Metab Syndr Obes. 2013; 6:493-9.
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        7. Yang C, Diiorio P, Jurczyk A, O'Sullivan-Murphy B, Urano F, Bortell R. Pathological endoplasmic reticulum stress mediated by the IRE1 pathway contributes to pre-insulitic beta cell apoptosis in a virus-induced rat model of type 1 diabetes. Diabetologia. 2013 Dec; 56(12):2638-46.
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        8. Sama RR, Ward CL, Kaushansky LJ, Lemay N, Ishigaki S, Urano F, Bosco DA. FUS/TLS assembles into stress granules and is a prosurvival factor during hyperosmolar stress. J Cell Physiol. 2013 Nov; 228(11):2222-31.
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        9. Jung DY, Chalasani U, Pan N, Friedline RH, Prosdocimo DA, Nam M, Azuma Y, Maganti R, Yu K, Velagapudi A, O'Sullivan-Murphy B, Sartoretto JL, Jain MK, Cooper MP, Urano F, Kim JK, Gray S. KLF15 is a molecular link between endoplasmic reticulum stress and insulin resistance. PLoS One. 2013; 8(10):e77851.
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        10. Kanekura K, Ishigaki S, Merksamer PI, Papa FR, Urano F. Establishment of a system for monitoring endoplasmic reticulum redox state in mammalian cells. Lab Invest. 2013 Nov; 93(11):1254-8.
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        11. Bonnycastle LL, Chines PS, Hara T, Huyghe JR, Swift AJ, Heikinheimo P, Mahadevan J, Peltonen S, Huopio H, Nuutila P, Narisu N, Goldfeder RL, Stitzel ML, Lu S, Boehnke M, Urano F, Collins FS, Laakso M. Autosomal dominant diabetes arising from a wolfram syndrome 1 mutation. Diabetes. 2013 Nov; 62(11):3943-50.
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        12. Hara T, Mahadevan J, Kanekura K, Hara M, Lu S, Urano F. Calcium Efflux From the Endoplasmic Reticulum Leads to ß-Cell Death. Endocrinology. 2014 Mar; 155(3):758-68.
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        13. Tohmonda T, Yoda M, Mizuochi H, Morioka H, Matsumoto M, Urano F, Toyama Y, Horiuchi K. The IRE1a-XBP1 pathway positively regulates parathyroid hormone (PTH)/PTH-related peptide receptor expression and is involved in pth-induced osteoclastogenesis. J Biol Chem. 2013 Jan 18; 288(3):1691-5.
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        14. Katsumata R, Ishigaki S, Katsuno M, Kawai K, Sone J, Huang Z, Adachi H, Tanaka F, Urano F, Sobue G. c-Abl inhibition delays motor neuron degeneration in the G93A mouse, an animal model of amyotrophic lateral sclerosis. PLoS One. 2012; 7(9):e46185.
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        15. Fonseca SG, Urano F, Weir GC, Gromada J, Burcin M. Wolfram syndrome 1 and adenylyl cyclase 8 interact at the plasma membrane to regulate insulin production and secretion. Nat Cell Biol. 2012 Oct; 14(10):1105-12.
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        16. Oslowski CM, Hara T, O'Sullivan-Murphy B, Kanekura K, Lu S, Hara M, Ishigaki S, Zhu LJ, Hayashi E, Hui ST, Greiner D, Kaufman RJ, Bortell R, Urano F. Thioredoxin-interacting protein mediates ER stress-induced ß cell death through initiation of the inflammasome. Cell Metab. 2012 Aug 8; 16(2):265-73.
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        17. Ishigaki S, Masuda A, Fujioka Y, Iguchi Y, Katsuno M, Shibata A, Urano F, Sobue G, Ohno K. Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions. Sci Rep. 2012; 2:529.
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        18. O'Sullivan-Murphy B, Urano F. ER stress as a trigger for ß-cell dysfunction and autoimmunity in type 1 diabetes. Diabetes. 2012 Apr; 61(4):780-1.
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        19. Matsuoka K, Hayashi S, Urano F, Zhu LJ, Okita H, Sago H, Nakazawa A. Squamous metaplasia in the cyst epithelium of type 1 congenital pulmonary airway malformation after thoracoamniotic shunt placement. Hum Pathol. 2012 Sep; 43(9):1413-7.
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        20. Alexandrov IM, Ivshina M, Jung DY, Friedline R, Ko HJ, Xu M, O'Sullivan-Murphy B, Bortell R, Huang YT, Urano F, Kim JK, Richter JD. Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance. PLoS Genet. 2012 Jan; 8(1):e1002457.
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        21. Meares GP, Hughes KJ, Naatz A, Papa FR, Urano F, Hansen PA, Benveniste EN, Corbett JA. IRE1-dependent activation of AMPK in response to nitric oxide. Mol Cell Biol. 2011 Nov; 31(21):4286-97.
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        22. Sharma M, Urano F, Jaeschke A. Cdc42 and Rac1 are major contributors to the saturated fatty acid-stimulated JNK pathway in hepatocytes. J Hepatol. 2012 Jan; 56(1):192-8.
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        23. Fonseca SG, Gromada J, Urano F. Endoplasmic reticulum stress and pancreatic ß-cell death. Trends Endocrinol Metab. 2011 Jul; 22(7):266-74.
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        24. Tohmonda T, Miyauchi Y, Ghosh R, Yoda M, Uchikawa S, Takito J, Morioka H, Nakamura M, Iwawaki T, Chiba K, Toyama Y, Urano F, Horiuchi K. The IRE1a-XBP1 pathway is essential for osteoblast differentiation through promoting transcription of Osterix. EMBO Rep. 2011 May; 12(5):451-7.
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        25. Oslowski CM, Urano F. Measuring ER stress and the unfolded protein response using mammalian tissue culture system. Methods Enzymol. 2011; 490:71-92.
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        26. Oslowski CM, Urano F. The binary switch that controls the life and death decisions of ER stressed ß cells. Curr Opin Cell Biol. 2011 Apr; 23(2):207-15.
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        27. Jurczyk A, Pino SC, O'Sullivan-Murphy B, Addorio M, Lidstone EA, Diiorio P, Lipson KL, Standley C, Fogarty K, Lifshitz L, Urano F, Mordes JP, Greiner DL, Rossini AA, Bortell R. A novel role for the centrosomal protein, pericentrin, in regulation of insulin secretory vesicle docking in mouse pancreatic beta-cells. PLoS One. 2010; 5(7):e11812.
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        28. Oslowski CM, Urano F. The binary switch between life and death of endoplasmic reticulum-stressed beta cells. Curr Opin Endocrinol Diabetes Obes. 2010 Apr; 17(2):107-12.
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        29. Ghosh R, Lipson KL, Sargent KE, Mercurio AM, Hunt JS, Ron D, Urano F. Transcriptional regulation of VEGF-A by the unfolded protein response pathway. PLoS One. 2010; 5(3):e9575.
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        30. Fonseca SG, Ishigaki S, Oslowski CM, Lu S, Lipson KL, Ghosh R, Hayashi E, Ishihara H, Oka Y, Permutt MA, Urano F. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells. J Clin Invest. 2010 Mar; 120(3):744-55.
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        31. Fonseca SG, Urano F, Burcin M, Gromada J. Stress hypERactivation in the ß-cell. Islets. 2010 Jan-Feb; 2(1):1-9.
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        32. Fonseca SG, Burcin M, Gromada J, Urano F. Endoplasmic reticulum stress in beta-cells and development of diabetes. Curr Opin Pharmacol. 2009 Dec; 9(6):763-70.
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        33. Kakiuchi C, Ishigaki S, Oslowski CM, Fonseca SG, Kato T, Urano F. Valproate, a mood stabilizer, induces WFS1 expression and modulates its interaction with ER stress protein GRP94. PLoS One. 2009; 4(1):e4134.
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        34. Pino SC, O'Sullivan-Murphy B, Lidstone EA, Thornley TB, Jurczyk A, Urano F, Greiner DL, Mordes JP, Rossini AA, Bortell R. Protein kinase C signaling during T cell activation induces the endoplasmic reticulum stress response. Cell Stress Chaperones. 2008 Dec; 13(4):421-34.
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        35. Lipson KL, Ghosh R, Urano F. The role of IRE1alpha in the degradation of insulin mRNA in pancreatic beta-cells. PLoS One. 2008; 3(2):e1648.
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        36. Luo D, He Y, Zhang H, Yu L, Chen H, Xu Z, Tang S, Urano F, Min W. AIP1 is critical in transducing IRE1-mediated endoplasmic reticulum stress response. J Biol Chem. 2008 May 2; 283(18):11905-12.
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        37. Fonseca SG, Lipson KL, Urano F. Endoplasmic reticulum stress signaling in pancreatic beta-cells. Antioxid Redox Signal. 2007 Dec; 9(12):2335-44.
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        38. Urano F. [ER stress signaling in pancreatic beta-cells]. Seikagaku. 2007 Nov; 79(11):1055-9.
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        39. Chambers KT, Unverferth JA, Weber SM, Wek RC, Urano F, Corbett JA. The role of nitric oxide and the unfolded protein response in cytokine-induced beta-cell death. Diabetes. 2008 Jan; 57(1):124-32.
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        40. Ishigaki S, Niwa J, Yamada S, Takahashi M, Ito T, Sone J, Doyu M, Urano F, Sobue G. Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity. Neurobiol Dis. 2007 Feb; 25(2):331-41.
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        41. Ohta E, Funayama M, Ichinose H, Toyoshima I, Urano F, Matsuo M, Tomoko N, Yukihiko K, Yoshino S, Yokoyama H, Shimazu H, Maeda K, Hasegawa K, Obata F. Novel mutations in the guanosine triphosphate cyclohydrolase 1 gene associated with DYT5 dystonia. Arch Neurol. 2006 Nov; 63(11):1605-10.
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        42. Hatori M, Doi H, Watanabe M, Sasano H, Hosaka M, Kotajima S, Urano F, Hata J, Kokubun S. Establishment and characterization of a clonal human extraskeletal Ewing's sarcoma cell line, EES1. Tohoku J Exp Med. 2006 Nov; 210(3):221-30.
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        43. Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 2006 Dec; 26(24):9220-31.
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        44. Lipson KL, Fonseca SG, Ishigaki S, Nguyen LX, Foss E, Bortell R, Rossini AA, Urano F. Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1. Cell Metab. 2006 Sep; 4(3):245-54.
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        45. Lipson KL, Fonseca SG, Urano F. Endoplasmic reticulum stress-induced apoptosis and auto-immunity in diabetes. Curr Mol Med. 2006 Feb; 6(1):71-7.
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        46. Furuya H, Murai H, Takasugi K, Ohyagi Y, Urano F, Kishi T, Ichinose H, Kira J. A case of late-onset Segawa syndrome (autosomal dominant dopa-responsive dystonia) with a novel mutation of the GTP-cyclohydrase I (GCH1) gene. Clin Neurol Neurosurg. 2006 Dec; 108(8):784-6.
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        47. Fonseca SG, Fukuma M, Lipson KL, Nguyen LX, Allen JR, Oka Y, Urano F. WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells. J Biol Chem. 2005 Nov 25; 280(47):39609-15.
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        48. Li XG, Okada T, Kodera M, Nara Y, Takino N, Muramatsu C, Ikeguchi K, Urano F, Ichinose H, Metzger D, Chambon P, Nakano I, Ozawa K, Muramatsu S. Viral-mediated temporally controlled dopamine production in a rat model of Parkinson disease. Mol Ther. 2006 Jan; 13(1):160-6.
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        49. Kanemoto S, Kondo S, Ogata M, Murakami T, Urano F, Imaizumi K. XBP1 activates the transcription of its target genes via an ACGT core sequence under ER stress. Biochem Biophys Res Commun. 2005 Jun 17; 331(4):1146-53.
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        50. Kubota K, Lee DH, Tsuchiya M, Young CS, Everett ET, Martinez-Mier EA, Snead ML, Nguyen L, Urano F, Bartlett JD. Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation. J Biol Chem. 2005 Jun 17; 280(24):23194-202.
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        51. Allen JR, Nguyen LX, Sargent KE, Lipson KL, Hackett A, Urano F. High ER stress in beta-cells stimulates intracellular degradation of misfolded insulin. Biochem Biophys Res Commun. 2004 Nov 5; 324(1):166-70.
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        52. Yoneda T, Benedetti C, Urano F, Clark SG, Harding HP, Ron D. Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. J Cell Sci. 2004 Aug 15; 117(Pt 18):4055-66.
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        53. Kikuchi A, Takeda A, Fujihara K, Kimpara T, Shiga Y, Tanji H, Nagai M, Ichinose H, Urano F, Okamura N, Arai H, Itoyama Y. Arg(184)His mutant GTP cyclohydrolase I, causing recessive hyperphenylalaninemia, is responsible for dopa-responsive dystonia with parkinsonism: a case report. Mov Disord. 2004 May; 19(5):590-3.
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        54. Urano F. [Stress signaling from the endoplasmic reticulum]. Tanpakushitsu Kakusan Koso. 2004 May; 49(7 Suppl):1002-5.
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        55. Matsushita K, Okita H, Suzuki A, Shimoda K, Fukuma M, Yamada T, Urano F, Honda T, Sano M, Iwanaga S, Ogawa S, Hata J, Umezawa A. Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene. Mol Cell Endocrinol. 2003 May 30; 203(1-2):105-16.
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        56. Chen J, Kuhlencordt P, Urano F, Ichinose H, Astern J, Huang PL. Effects of chronic treatment with L-arginine on atherosclerosis in apoE knockout and apoE/inducible NO synthase double-knockout mice. Arterioscler Thromb Vasc Biol. 2003 Jan 1; 23(1):97-103.
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        57. Urano F, Calfon M, Yoneda T, Yun C, Kiraly M, Clark SG, Ron D. A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response. J Cell Biol. 2002 Aug 19; 158(4):639-46.
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        58. Yoneda T, Urano F, Ron D. Transmission of proteotoxicity across cellular compartments. Genes Dev. 2002 Jun 1; 16(11):1307-13.
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        59. Yoshizawa J, Maie M, Eto T, Higashimoto Y, Saito T, Horie H, Urano F. A case of intra-abdominal desmoplastic small-round-cell tumor with elevated serum CA125. Pediatr Surg Int. 2002 May; 18(4):238-40.
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        60. Yabe H, Fukuma M, Urano F, Yoshida K, Kato S, Toyama Y, Hata J, Umezawa A. Lack of matrix metalloproteinase (MMP)-1 and -3 expression in Ewing sarcoma may be due to loss of accessibility of the MMP regulatory element to the specific fusion protein in vivo. Biochem Biophys Res Commun. 2002 Apr 26; 293(1):61-71.
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        61. Harding HP, Calfon M, Urano F, Novoa I, Ron D. Transcriptional and translational control in the Mammalian unfolded protein response. Annu Rev Cell Dev Biol. 2002; 18:575-99.
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        62. Kawasaki H, Suemori H, Mizuseki K, Watanabe K, Urano F, Ichinose H, Haruta M, Takahashi M, Yoshikawa K, Nishikawa S, Nakatsuji N, Sasai Y. Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc Natl Acad Sci U S A. 2002 Feb 5; 99(3):1580-5.
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        63. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature. 2002 Jan 3; 415(6867):92-6.
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