BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE John C. Hutton Professor and Research Director eRA COMMONS USER NAME HUTTON.JOHN EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION University of New South Wales, Sydney, Australia University of New South Wales, Sydney, Australia DEGREE (if applicable) YEAR(s) BSc PhD 1969 1974 FIELD OF STUDY Biochemistry/Physiology Biochemistry A. Positions and Honors: 1/73 - 12/73 Research Officer, School of Biochemistry, U. N.S.W. Sydney, Australia. 1974 - 1976 Visiting Research Scientist, Instituto de Genetica Humana, Universidad Mayor de San Andres, La Paz, Bolivia. 1976 - 1979 Postdoctoral Research Fellow, Laboratoire de Medecine Experimentale, Universite Libre de Bruxelles, Belgium. 1979 - 1980 C.J. Martin Research Fellow, University of Cambridge, Cambridge, U.K. 1981 - 1983 Senior Research Associate, University of Cambridge, Cambridge, U.K. 1983 - 1989 BDA Senior Research Fellow, University of Cambridge, Cambridge, U.K. 1985 - 1985 Research Scientist, Hagedorn Research Laboratories, Gentofte, Denmark. 1991 - 1992 Visiting Professor, Hormone Research Institute, UC- San Francisco. 1989 - 1995 Reader, University of Cambridge, Cambridge, U.K. 1996 - present Director of Research, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center (UCHSC), Denver, CO 1996 - 1997 Ad hoc, NIH/ NIDDK Endocrinology Study Section 1996 - 1999 Member, Medical Science Review Committee, Juvenile Diabetes Foundation International 1997 - present Member, NIH/ NIDDK Endocrinology Study Section 1996 - present Professor of Pediatrics, UCHSC, Denver, CO, 1996 - present Professor of Cellular & Structural Biology, UCHSC, Denver, CO 1965 1974 1976 1979 1980 1983 1988 1988 Australian Estates Award Fellow of Bolivian Academy of Sciences Nature Travel Award (journalism relating to Third World science) C.J. Martin Fellowship Research Fellowship, Wolfson College, University of Cambridge British Diabetic Association Senior Research Fellowship University Medal of the University of Granada, Spain Oskar Minkowski Prize (for distinguished research in the field of diabetes in Europe) B. Selected peer-reviewed publications: (selected from 150 publications) 1. Guest P C, Bailyes E M and Hutton J C (1997) Endoplasmic reticulum Ca2+ is important for the proteolytic processing and intracellular transport of proinsulin in the pancreatic beta-cell. Biochem. J. 323: 445-450. 2. Hutton JC. (1997) Tetrahymena: The key to the genetic analysis of the regulated pathway of polypeptide secretion? Proc Natl Acad Sci USA 94: 10490-10492. 3. Pouli AE, Karagenc N, Wasmeier C, Hutton JC, Bright N, Arden S, Schofield JG and Rutter GA. (1998) A phogrin-aequorin chimaera to image free Ca2+ in the vicinity of secretory granules. BiochemJ 330: 1399-1404. 4. Pouli AE, Emmanouilidou E, Zhao C, Wasmeier C, Hutton JC and Rutter GA. (1998) Secretory-granule dynamics visualized in vivo with a phogrin-green fluorescent protein chimaera. Biochem J. 333: 193199. 5. Creemers JW, Jackson RS and Hutton JC. (1998) Molecular and cellular regulation of prohormone processing. Semin Cell Dev Biol 9: 3-10. 6. Arden SD, Zahn T, Steegers S, Webb S, Bergman B, O’Brien RM and Hutton JC. (1999) Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein. Diabetes 48: 531-542. 7. Ebert DH, Bischof LJ, Streeper RS, Chapman SC, Svitek CA, Goldman JK, Mathews CE, Leiter EH, Hutton JC and O’Brien RM. (1999) Structure and promoter activity of an islet-specific glucose-6phosphatase catalytic subunit-related gene. Diabetes 48: 543-551. 8. Hurlbert MS, Zhou W, Wasmeier C, Kaddis FG, Hutton JC and Freed CR. (1999) Mice transgenic for an expanded CAG repeat in the Huntington’s disease gene develop diabetes. Diabetes 48: 649-651. 9. Kelemen K, Crawford ML, Gill RG, Hutton JC and Wegmann D. (1999) Cellular immune response to phogrin in the NOD mouse: Cloned T cells cause destruction of islet transplants. Diabetes, 48: 15291534. 10. Wasmeier C and Hutton JC. (1999) Secretagogue-dependent phosphorylation of phogrin, an insulin granule membrane protein tyrosine phosphatase homologue. Biochem J 341: 563-569 11. Tree TIM, O’Byrne D, Tremble JM, MacFarlane WM, Haskins K, James RFL, Docherty K, Hutton JC and Banga JP. (2000) Evidence for recognition of novel islet T cell antigens by granule specific T cell lines from new onset type 1 diabetes. Clin Exp Immunol 121: 100-105. 12. Park YS, Kawasaki E, Kelemen K, Yu L, Schiller MR, Rewers M, Mizuta M, Eisenbarth GS and Hutton JC. (2000) Humoral autoreactivity to an alternatively spliced variant of ICA512/IA-2 in type 1 diabetes. Diabetologia 43: 1293-1301. 13. Zahn T R, MacMorris M A, Dong W, Day R and Hutton J C. (2001) IDA-1, a Caenorhabditis elegans homologue of the diabetic autoantigens IA-2 and phogrin, is expressed in peptideric neurons in the worm. J of Comparative Neurology 429: 127-143. 14. Diez J, Park Y S, Zeller M, Brown D, Garaza, D, Ricordi C, Hutton J, Eisenbarth G S and Pugliese A. (2001) Differential splicing of the IA-2 autoantigen mRNA in pancreas and lymphoid organs as a predisposing factor to autoimmunity in type 1 diabetes. Diabetes 50: 895-900. 15. Kelemen, K, Wegmann D R and Hutton J C. (2001) T cell epitope analysis on the autoantigen phogrin (IA-2) in the non obese diabetic mouse. Diabetes 50: 1729-1734. 16. Martin C C, Bischof L J, Bergman B, Hornbuckle L A, Hilliker C, Frigeri C, Wahl D, Svitek C A, Wong R, Goldman J K, Oeser J K, Leprêtre F, Froguel P, O’Brien R M and Hutton J C. (2001) Cloning and characterization of the Rat and Human Islet-Specific Glucose-6-Phosphatase Catalytic Subunit-Related Protein (IGRP) Genes. J of Biological Chemistry, 276: 25197-25207. 17. Bischof LJ, Martin CC, Svitek CA, Stadelmaier BT, Hornbuckle LA, Goldman JK, Oeser JK, Hutton JC and O’Brien RM. (2001) Characterization of the mouse islet-specific glucose-6-phosphatase catalytic subunit-related protein gene promoter by in situ footprinting. Diabetes 50: 502-514. 18. Wasmeier C and Hutton J C. (2001) Secretagogue-dependent phosphorylation of the insulin granule membrane protein phogrin is mediated by cAMP-dependent protein kinase. J of Biological Chemistry 276: 31919-31928. 19. Wasmeier C, Bright NA and Hutton JC. (2002) The lumenal domain of the integral membrane protein phogrin mediates targeting to secretory granules. Traffic, 3:654-665. 20. Achenbach P, Kelemen K, Wegmann DR, and Hutton JC (2002) Spontaneous peripheral T-cell responses to the IA-2 (phogrin) autoantigen in young nonobese diabetic mice. J of Autoimmunity 19(3): 111-116. 21. Jambal P, Masterson S, Nesterova A, Bouchard R, Bergman B, Hutton JC, Boxer LM, Reusch JE-B and Pugazhenthi S. (2003) Cytokine-mediated downregulation of the transcription factor CREB in pancreatic -cells. J Biol Chem. 2003 Jun 20;278(25):23055-65. 22. Nicolls MR, D’Antonio JM, Hutton JC, Gill RG, Czwornog JL and Duncan MW. (2003) Proteomics as a tool for discovery: Proteins implicated in Alzheimer’s Disease are highly expressed in normal pancreatic islets. J of Proteome Research 2:199-205. 23. Hutton JC, Eisenbarth GS. (2003) A pancreatic ß-cell-specific homolog of glucose-6-phosphatase emerges as a major target of cell-mediated autoimmunity in diabetes. Proc Natl Acad Sci U S A. 100(15):8626-8628 24. Boustead JN, Martin CC, Oeser JK, Svitek CA, Hunter SI, Hutton JC and O'Brien RM. (2004) Identification and characterization of a cDNA and gene encoding the mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein. Journal of Molecular Endocrinology, 32: 33-53. 25. Kelemen K, Gottlieb PA, Putnam AL, Davidson HW, Wegmann DR and Hutton JC (2004) HLA-DQ8 associated T cell responses to the diabetes autoantigen phogrin (IA-2) in human prediabetes. J. Immunol 172: 3955-3962. 26. Zahn TR, Angleson JK, MacMorris MA, Domke E, Hutton JF, Schwartz C and Hutton JC (2004) Dense core vesicle dynamics in C. elegans neurons and the role of kinesin UNC-104. Traffic 5: 544-559. 27. Frigeri C, Martin CC, Svitek CA, Oeser JK, Hutton JC, Gannon M, O'Brien RM. (2004) The proximal islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen promoter is sufficient to initiate but not maintain transgene expression in mouse islets in vivo. Diabetes. 53(7):1754-64. 28. Nakayama M, Moriyama H, Abiru N, Babu SR, Sikora K, Li M, Miao D, Hutton JC, Elliott JF, Eisenbarth GS (2004) Establishment of Native Insulin-Negative NOD Mice and the Methodology to Distinguish Specific Insulin Knockout Genotypes and a B:16 Alanine Preproinsulin Transgene. Ann N Y Acad Sci. Dec;1037:193-198. 29. Limesand SW, Jensen J, Hutton JC, Hay Jr WW. (2005) Diminished ß-Cell Replication Contributes to Reduced ß-Cell Mass in Fetal Sheep with Intrauterine Growth Restriction. Am J Physiol Regul Integra Comp Physiol. May;88(5):R1297-305. 30. Wasmeier C, Burgos PV, Trudeau T, Davidson HW, Hutton JC (2005) An extended tyrosine-targeting motif for endocytosis and recycling of the dense core vesicle membrane protein phogrin. Traffic. Jun;6(6):474-87. 31. Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, Yu L, Wegmann D, Hutton JC, Elliott JF, Eisenbarth GS (2005) Gene Rescue of insulin null autoimmune mice: primacy of an insulin peptide for type 1 diabetes. Nature 435:220-223 32. Dogra RS, Vaidyanathan P, Prabakar KR, Marshall K, Hutton JC, Pugliese A (2006) Alternative Splicing of the Islet Specific Glucose-6-phosphatase Catalytic-subunit Related Protein (IGRP) Gene Results in Differential Expression in Human Thymus and Spleen Compared to Pancreas. Diabetologia, 49:953-957 33. Hutton JC, Wong R, Davidson HW (2006) Curr. Protocols in Cell Biology (in press) 34. Limesand SW, Rozance PJ, Zerbe GO, Hutton JC, Hay WW Jr. (2006) Attenuated insulin release and storage in fetal sheep pancreatic islets with intrauterine growth restriction. Endocrinology. 2006 Mar;147(3):1488-9 35. Gianani R, Putnam A, Still T, Yu L, Miao D, Gill RG, Beilke J, Supon P, Valentine A, Iveson A, Dunn S, Eisenbarth GS, Hutton J, Gottlieb P, Wiseman A (2006) Initial results of screening of non - diabetic organ donors for expression of islet autoantibodies. J Clin Endocrinol Metab 91:1855-1861 36. Babaya N, Nakayama M, Moriyama H, Gianani R, Still T, Hutton JC, Eisenbarth GS (2006) A new model of insulin gene deficient diabetes: male NOD mice with a single copy of insulin 1 and no insulin 2 gene Diabetologia 49:1222-1228 37. Juhl J, Wong R, Mellizer G, Sarkar S,,Gradwohl G, Jensen J, Hutton JC (2006) Definition of the pancreatic islet-specific transcriptome in mouse (submitted) 38. Sarkar SA, Wong R, Hackl SE, Moua O, Valentine A, Gill R, Davidson HW, Hutton JC (2007) Induction of Indoleamine 2,3, dioxygenase by interferon gamma in human islets Diabetes (in press) 39. Wang Y, Oeser JK, Yang C, Sarkar S, Hackl SI, Hasty AH, McGuiness OP, Hutton JC, O’Brien RM (2006) Deletion of the gene encoding the mouse ubiquitously expressed glucose-6-phosphataserelated subunit protein (UGRP)/G6Pase-ß results in lowered plasma cholesterol and elevated glucagon J. Biol Chem (online) 40. Wang Y, Martin CC, Oeser JK, Sarkar S, McGuiness OP, Hutton JC, Jacobsen PB, O’Brien RM (2007) Deletion of the gene encoding the islet-specific glucose-6-phosphatase-related subunit protein (IGRP) autoantigen results in mild fasting hypoglycemia Diabetologia (in press) 41. Wang,Y, Flemming BP, Allen SR, Martin CC, Walters J, Oeser JK, Hutton JC, O’Brien RM (2007) Intron sequences of islet-specific glucose-6-phosphatase-related subunit protein (IGRP) are required for postnatal expression of promoter transgene constructs in vivo. (in press)