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    Rita B Bortell PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    368 Plantation Street, AS7-2055
    Worcester MA 01605
    Phone508-856-3788
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

        Overview 
        Narrative

        Academic Background

        B.S., University of Florida, 1975
        M.S., University of Florida, 1981
        Ph.D., University of Florida College of Medicine, 1987

        Pathogenesis of autoimmune diabetes

        A major goal of our research is to understand the etiology and pathogenesis of diabetes, with a particular focus on cellular processes which contribute to pancreatic beta cell dysfunction. In one approach we utilize rodent models of spontaneous and virus-induced autoimmune type 1 diabetes to investigate beta cell endoplasmic reticulum (ER) stress during induction of the disease. We employ molecular, biochemical and cellular approaches to elucidate diabetes pathogenesis so as to develop therapies to prevent or reverse the disease. A second approach is focused on developing methods to increase the survival and function of human pancreatic islet transplants to cure those individuals who are already diabetic. For these studies we use novel strains of immunodeficient mice that can be engrafted with functional human cells and tissues, including human pancreatic islets and/or human immune systems. We are utilizing these “humanized” mice to investigate human beta cell function, regeneration and survival in response to various in vivo settings relevant to both type 1 and type 2 diabetes. Such approaches allow us to uncover molecular mechanisms important in preserving human beta cell function and survival, thus facilitating the translation of these discoveries into the clinic.



        Bibliographic 
        selected publications
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        1. diIorio P, Rittenhouse AR, Bortell R, Jurczyk A. Role of cilia in normal pancreas function and in diseased states. Birth Defects Res C Embryo Today. 2014 Jun; 102(2):126-38.
          View in: PubMed
        2. Jurczyk A, Bortell R, Alonso LC. Human ß-cell regeneration: progress, hurdles, and controversy. Curr Opin Endocrinol Diabetes Obes. 2014 Apr; 21(2):102-8.
          View in: PubMed
        3. 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.
          View in: PubMed
        4. Yang C, Jurczyk A, diIorio P, Norowski E, Brehm MA, Grant CW, Guberski DL, Greiner DL, Bortell R. Salicylate prevents virus-induced type 1 diabetes in the BBDR rat. PLoS One. 2013; 8(10):e78050.
          View in: PubMed
        5. 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.
          View in: PubMed
        6. 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.
          View in: PubMed
        7. Bortell R, Yang C. The BB rat as a model of human type 1 diabetes. Methods Mol Biol. 2012; 933:31-44.
          View in: PubMed
        8. Kruger AJ, Yang C, Tam SW, Hinerfeld D, Evans JE, Green KM, Leszyk J, Yang K, Guberski DL, Mordes JP, Greiner DL, Rossini AA, Bortell R. Haptoglobin as an early serum biomarker of virus-induced autoimmune type 1 diabetes in biobreeding diabetes resistant and LEW1.WR1 rats. Exp Biol Med (Maywood). 2010 Nov; 235(11):1328-37.
          View in: PubMed
        9. Jurczyk A, Roy N, Bajwa R, Gut P, Lipson K, Yang C, Covassin L, Racki WJ, Rossini AA, Phillips N, Stainier DY, Greiner DL, Brehm MA, Bortell R, diIorio P. Dynamic glucoregulation and mammalian-like responses to metabolic and developmental disruption in zebrafish. Gen Comp Endocrinol. 2011 Jan 15; 170(2):334-45.
          View in: PubMed
        10. Kruger AJ, Yang C, Lipson KL, Pino SC, Leif JH, Hogan CM, Whalen BJ, Guberski DL, Lee Y, Unger RH, Greiner DL, Rossini AA, Bortell R. Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats. Autoimmunity. 2011 Mar; 44(2):137-48.
          View in: PubMed
        11. 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.
          View in: PubMed
        12. Brehm MA, Bortell R, Diiorio P, Leif J, Laning J, Cuthbert A, Yang C, Herlihy M, Burzenski L, Gott B, Foreman O, Powers AC, Greiner DL, Shultz LD. Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice. Diabetes. 2010 Sep; 59(9):2265-70.
          View in: PubMed
        13. Pino SC, Kruger AJ, Bortell R. The role of innate immune pathways in type 1 diabetes pathogenesis. Curr Opin Endocrinol Diabetes Obes. 2010 Apr; 17(2):126-30.
          View in: PubMed
        14. Pino SC, O'Sullivan-Murphy B, Lidstone EA, Yang C, Lipson KL, Jurczyk A, diIorio P, Brehm MA, Mordes JP, Greiner DL, Rossini AA, Bortell R. CHOP mediates endoplasmic reticulum stress-induced apoptosis in Gimap5-deficient T cells. PLoS One. 2009; 4(5):e5468.
          View in: PubMed
        15. Chopra P, Diiorio P, Pino SC, Wilson SB, Phillips NE, Mordes JP, Rossini AA, Greiner DL, Shultz LD, Bortell R. Failure of alpha-galactosylceramide to prevent diabetes in virus-inducible models of type 1 diabetes in the rat. In Vivo. 2009 Mar-Apr; 23(2):195-201.
          View in: PubMed
        16. Bortell R, Pino SC, Greiner DL, Zipris D, Rossini AA. Closing the circle between the bedside and the bench: Toll-like receptors in models of virally induced diabetes. Ann N Y Acad Sci. 2008 Dec; 1150:112-22.
          View in: PubMed
        17. 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.
          View in: PubMed
        18. 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.
          View in: PubMed
        19. Morrison AR, Moss J, Stevens LA, Evans JE, Farrell C, Merithew E, Lambright DG, Greiner DL, Mordes JP, Rossini AA, Bortell R. ART2, a T cell surface mono-ADP-ribosyltransferase, generates extracellular poly(ADP-ribose). J Biol Chem. 2006 Nov 3; 281(44):33363-72.
          View in: PubMed
        20. Zheng X, Morrison AR, Chung AS, Moss J, Bortell R. Substrate specificity of soluble and membrane-associated ADP-ribosyltransferase ART2.1. J Cell Biochem. 2006 Jul 1; 98(4):851-60.
          View in: PubMed
        21. Todd DJ, Forsberg EM, Greiner DL, Mordes JP, Rossini AA, Bortell R. Deficiencies in gut NK cell number and function precede diabetes onset in BB rats. J Immunol. 2004 May 1; 172(9):5356-62.
          View in: PubMed
        22. Mordes JP, Bortell R, Blankenhorn EP, Rossini AA, Greiner DL. Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR J. 2004; 45(3):278-91.
          View in: PubMed
        23. Pandarpurkar M, Wilson-Fritch L, Corvera S, Markholst H, Hornum L, Greiner DL, Mordes JP, Rossini AA, Bortell R. Ian4 is required for mitochondrial integrity and T cell survival. Proc Natl Acad Sci U S A. 2003 Sep 2; 100(18):10382-7.
          View in: PubMed
        24. Bortell R, Moss J, McKenna RC, Rigby MR, Niedzwiecki D, Stevens LA, Patton WA, Mordes JP, Greiner DL, Rossini AA. Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: role of cell surface NAD glycohydrolase and pyrophosphatase activities. J Immunol. 2001 Aug 15; 167(4):2049-59.
          View in: PubMed
        25. Bortel R, Waite DJ, Whalen BJ, Todd D, Leif JH, Lesma E, Moss J, Mordes JP, Rossini AA, Greiner DL. Levels of Art2+ cells but not soluble Art2 protein correlate with expression of autoimmune diabetes in the BB rat. Autoimmunity. 2001 May; 33(3):199-211.
          View in: PubMed
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