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    Stephen Gitelman, MD

    TitleProfessor
    SchoolUCSF School of Medicine
    DepartmentPediatrics
    Address513 Parnassus Ave, Med Sci
    San Francisco CA 94143
    Phone415-476-3748

       Overview 
       Overview
      I am involved in a variety of different translational and clinical research projects, most related to diabetes. A number of the on-going studies are attempts to alter the course of autoimmune-mediated type 1 diabetes, often via immunomodulation, in order to preserve endogenous beta cell function. Some of the recent and on-going projects are described below.

      Most of this work occurs in multi-center clinical trials. I am the Clinical Center director for the NIH sponsored program TrialNet, a multi-center research consortium that develops trials to delay or prevent the onset of type 1 diabetes in those at risk, or prolong endogenous insulin secretion (the honeymoon phase) in those with new onset disease. UCSF is one of 14 national centers for this 7-year study. Current studies include:
      -natural history study to screen and predict who might develop type 1 diabetes
      -a prevention trial with omega 3 fatty acids to determine if treatment during pregnancy or shortly after birth can serve as a primary means to prevent type 1 diabetes
      -a new onset diabetes trial with mycophenolate mofetil with our without IL-2 receptor monoclonal antibody to determine if this will preserve endogenous insulin secretion
      -a new onset study with anti-CD20 monoclonal antibody to determine if this will preserve endogenous insulin secretion
      The consortium is continuing to develop additional prevention and new onset studies over time.

      In addition, I have served as the site director for a novel study evaluating the role of an anti-CD3 monoclonal antibody in prolonging the honeymoon phase in those with new onset type 1 diabetes. The initial phase 1 / 2 study results were published in the N Engl J Med 2002, and our 2 year follow-up data was just published (Diabetes 2005). These exciting results were confirmed in an independent study with a related drug in Europe, and have spawned a series of studies to build on these initial findings. We are now launching an NIH-sponsored phase 2 study for new onset diabetes, evaluating the efficacy of antibody treatment every 12 months for 2 courses. In addition to these efforts, we have several additional NIH-funded new onset type 1 diabetes studies that will soon begin. We are evaluating the window of opportunity for anti-CD3 therapy, with a trial planned for subjects from 4 to 12 months from diagnosis. We are developing clinical trials the assess the effect of anti-CD3 therapy coupled with antigen, and another study coupling with an incretin hormone analgoue, exenatide, which may help with beta cell regeneration. Finally, I am the study principal investigator for a multi-center new onset type 1 diabetes trial with anti-thymocyte globulin, sponsored by the Immune Tolerance Network.

      I am partnering with other members of the UCSF Diabetes Center to pursue other clinical trials, and translational studies that may help us better understand the pathogenesis of type 1 diabetes. Such studies include development of T cell assays; characterization of patients with novel disorders in carbohydrate metabolism; possible use of T regulatory cells as an immunotherapy. As technology advances, we anticipate to one day be able to use beta cells developed from stem cells as a definitive treatment for type 1 diabetes.


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       Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Orban T, Bundy B, Becker DJ, Dimeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Marks JB, Monzavi R, Moran A, Peakman M, Raskin P, Russell WE, Schatz D, Wherrett DK, Wilson DM, Krischer JP, Skyler JS. Costimulation Modulation With Abatacept in Patients With Recent-Onset Type 1 Diabetes: Follow-up 1 Year After Cessation of Treatment. Diabetes Care. 2014 Apr; 37(4):1069-75.
        View in: PubMed
      2. Rigby MR, Dimeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Patel CM, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Moran A, Russell WE, Pinckney A, Keyes-Elstein L, Howell M, Aggarwal S, Lim N, Phippard D, Nepom GT, McNamara J, Ehlers MR. Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Diabetes Endocrinol. 2013 Dec; 1(4):284-94.
        View in: PubMed
      3. Pescovitz MD, Greenbaum CJ, Bundy B, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, Moran A, Raskin P, Rodriguez H, Schatz DA, Wherrett DK, Wilson DM, Krischer JP, Skyler JS. B-Lymphocyte Depletion With Rituximab and ß-Cell Function: Two-Year Results. Diabetes Care. 2014 Feb; 37(2):453-9.
        View in: PubMed
      4. Gitelman SE, Gottlieb PA, Rigby MR, Felner EI, Willi SM, Fisher LK, Moran A, Gottschalk M, Moore WV, Pinckney A, Keyes-Elstein L, Aggarwal S, Phippard D, Sayre PH, Ding L, Bluestone JA, Ehlers MR. Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2013 Dec; 1(4):306-16.
        View in: PubMed
      5. Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, Boyle KD, Keyes-Elstein L, Aggarwal S, Phippard D, Sayre PH, McNamara J, Bluestone JA. Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes. 2013 Nov; 62(11):3766-74.
        View in: PubMed
      6. Thomas HR, Gitelman SE. Altering the course of type 1 diabetes: an update on prevention and new-onset clinical trials. Pediatr Diabetes. 2013 Aug; 14(5):311-21.
        View in: PubMed
      7. Benedict KA, Moassesfar S, Adi S, Gitelman SE, Brennan JL, McEnhill M, Stock PG, Portale AA, Posselt AM. Combined pancreatic islet and kidney transplantation in a child with unstable type 1 diabetes and end-stage renal disease. Am J Transplant. 2013 Aug; 13(8):2207-10.
        View in: PubMed
      8. Gerard-Gonzalez A, Gitelman SE, Cheng P, Dubose SN, Miller KM, Olson BA, Redondo MJ, Steck AK, Beck RW. Comparison of autoantibody-positive and autoantibody-negative pediatric participants enrolled in the T1D Exchange clinic registry. J Diabetes. 2013 Jun; 5(2):216-23.
        View in: PubMed
      9. Moran A, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Greenbaum CJ, Herold KC, Marks JB, Raskin P, Sanda S, Schatz D, Wherrett DK, Wilson DM, Krischer JP, Skyler JS. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet. 2013 Jun 1; 381(9881):1905-15.
        View in: PubMed
      10. Lenders CM, Lee PD, Feldman HA, Wilson DM, Abrams SH, Gitelman SE, Klish WJ, Wertz MS, Taylor GA, Alongi RT, Chen TC, Holick MF. A cross-sectional study of osteocalcin and body fat measures among obese adolescents. Obesity (Silver Spring). 2013 Apr; 21(4):808-14.
        View in: PubMed
      11. Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune therapy and ß-cell death in type 1 diabetes. Diabetes. 2013 May; 62(5):1676-80.
        View in: PubMed
      12. Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, Sherr J, Rosenthal SM, Adi S, Jalaludin MY, Michels AW, Dziura J, Bluestone JA. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013 Feb; 56(2):391-400.
        View in: PubMed
      13. Greenbaum CJ, Beam CA, Boulware D, Gitelman SE, Gottlieb PA, Herold KC, Lachin JM, McGee P, Palmer JP, Pescovitz MD, Krause-Steinrauf H, Skyler JS, Sosenko JM. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite Type 1 Diabetes TrialNet data. Diabetes. 2012 Aug; 61(8):2066-73.
        View in: PubMed
      14. Cheung CC, Cadnapaphornchai MA, Ranadive SA, Gitelman SE, Rosenthal SM. Persistent elevation of urine aquaporin-2 during water loading in a child with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by a R137L mutation in the V2 vasopressin receptor. Int J Pediatr Endocrinol. 2012; 2012(1):3.
        View in: PubMed
      15. Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Marks JB, Monzavi R, Moran A, Raskin P, Rodriguez H, Russell WE, Schatz D, Wherrett D, Wilson DM, Krischer JP, Skyler JS. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jul 30; 378(9789):412-9.
        View in: PubMed
      16. Wherrett DK, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Herold KC, Marks JB, Monzavi R, Moran A, Orban T, Palmer JP, Raskin P, Rodriguez H, Schatz D, Wilson DM, Krischer JP, Skyler JS. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet. 2011 Jul 23; 378(9788):319-27.
        View in: PubMed
      17. Glaser NS, Geller DH, Haqq A, Gitelman S, Malloy M. Detecting and treating hyperlipidemia in children with type 1 diabetes mellitus: are standard guidelines applicable to this special population? Pediatr Diabetes. 2011 Jun; 12(4 Pt 2):442-59.
        View in: PubMed
      18. Sullivan MM, O'Brien CR, Gitelman SE, Shapiro SE, Rushakoff RJ. Impact of an interactive online nursing educational module on insulin errors in hospitalized pediatric patients. Diabetes Care. 2010 Aug; 33(8):1744-6.
        View in: PubMed
      19. Rochdi MD, Vargas GA, Carpentier E, Oligny-Longpré G, Chen S, Kovoor A, Gitelman SE, Rosenthal SM, von Zastrow M, Bouvier M. Functional characterization of vasopressin type 2 receptor substitutions (R137H/C/L) leading to nephrogenic diabetes insipidus and nephrogenic syndrome of inappropriate antidiuresis: implications for treatments. Mol Pharmacol. 2010 May; 77(5):836-45.
        View in: PubMed
      20. Cho YH, Gitelman S, Rosenthal S, Ambler G. Long-term outcomes in a family with nephrogenic syndrome of inappropriate antidiuresis. Int J Pediatr Endocrinol. 2009; 2009:431527.
        View in: PubMed
      21. Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, McGee PF, Moran AM, Raskin P, Rodriguez H, Schatz DA, Wherrett D, Wilson DM, Lachin JM, Skyler JS. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009 Nov 26; 361(22):2143-52.
        View in: PubMed
      22. Gitelman SE, Haller MJ, Schatz D. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2009 Aug 12; 302(6):624; author reply 624-5.
        View in: PubMed
      23. Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, Lee PD, Abrams SH, Gitelman SE, Wertz MS, Klish WJ, Taylor GA, Chen TC, Holick MF. Relation of body fat indexes to vitamin D status and deficiency among obese adolescents. Am J Clin Nutr. 2009 Sep; 90(3):459-67.
        View in: PubMed
      24. Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, Sayre P, Bianchine P, Wong E, Seyfert-Margolis V, Bourcier K, Bluestone JA. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009 Aug; 132(2):166-73.
        View in: PubMed
      25. Huang EA, Gitelman SE. The effect of oral alpha-lipoic acid on oxidative stress in adolescents with type 1 diabetes mellitus. Pediatr Diabetes. 2008 Jun; 9(3 Pt 2):69-73.
        View in: PubMed
      26. Bremer AA, Nobuhara KK, Gitelman SE. Congenital hyperinsulinism in an infant caused by a macroscopic insulin-producing lesion. J Pediatr Endocrinol Metab. 2007 Mar; 20(3):437-40.
        View in: PubMed
      27. Rosenthal SM, Feldman BJ, Vargas GA, Gitelman SE. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD): a paradigm for activating mutations causing endocrine dysfunction. Pediatr Endocrinol Rev. 2006 Dec; 4 Suppl 1:66-70.
        View in: PubMed
      28. Seyfert-Margolis V, Gisler TD, Asare AL, Wang RS, Dosch HM, Brooks-Worrell B, Eisenbarth GS, Palmer JP, Greenbaum CJ, Gitelman SE, Nepom GT, Bluestone JA, Herold KC. Analysis of T-cell assays to measure autoimmune responses in subjects with type 1 diabetes: results of a blinded controlled study. Diabetes. 2006 Sep; 55(9):2588-94.
        View in: PubMed
      29. Gitelman SE, Feldman BJ, Rosenthal SM. Nephrogenic syndrome of inappropriate antidiuresis: a novel disorder in water balance in pediatric patients. Am J Med. 2006 Jul; 119(7 Suppl 1):S54-8.
        View in: PubMed
      30. Huang EA, Feldman BJ, Schwartz ID, Geller DH, Rosenthal SM, Gitelman SE. Oral urea for the treatment of chronic syndrome of inappropriate antidiuresis in children. J Pediatr. 2006 Jan; 148(1):128-31.
        View in: PubMed
      31. Sapru A, Gitelman SE, Bhatia S, Dubin RF, Newman TB, Flori H. Prevalence and characteristics of type 2 diabetes mellitus in 9-18 year-old children with diabetic ketoacidosis. J Pediatr Endocrinol Metab. 2005 Sep; 18(9):865-72.
        View in: PubMed
      32. Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun; 54(6):1763-9.
        View in: PubMed
      33. Feldman BJ, Rosenthal SM, Vargas GA, Fenwick RG, Huang EA, Matsuda-Abedini M, Lustig RH, Mathias RS, Portale AA, Miller WL, Gitelman SE. Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med. 2005 May 5; 352(18):1884-90.
        View in: PubMed
      34. Wilson DM, Buckingham BA, Kunselman EL, Sullivan MM, Paguntalan HU, Gitelman SE. A two-center randomized controlled feasibility trial of insulin pump therapy in young children with diabetes. Diabetes Care. 2005 Jan; 28(1):15-9.
        View in: PubMed
      35. Conrad SC, Mastrototaro JJ, Gitelman SE. The use of a continuous glucose monitoring system in hypoglycemic disorders. J Pediatr Endocrinol Metab. 2004 Mar; 17(3):281-8.
        View in: PubMed
      36. Steele C, Hagopian WA, Gitelman S, Masharani U, Cavaghan M, Rother KI, Donaldson D, Harlan DM, Bluestone J, Herold KC. Insulin secretion in type 1 diabetes. Diabetes. 2004 Feb; 53(2):426-33.
        View in: PubMed
      37. Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30; 346(22):1692-8.
        View in: PubMed
      38. Conrad SC, McGrath MT, Gitelman SE. Transition from multiple daily injections to continuous subcutaneous insulin infusion in type 1 diabetes mellitus. J Pediatr. 2002 Feb; 140(2):235-40.
        View in: PubMed
      39. Greenspan LC, Gitelman SE, Leung MA, Glidden DV, Mathias RS. Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis. Pediatr Nephrol. 2002 Jan; 17(1):1-5.
        View in: PubMed
      40. Roll U, Turck CW, Gitelman SE, Rosenthal SM, Nolte MS, Masharani U, Ziegler AG, Baekkeskov S. Peptide mapping and characterisation of glycation patterns of the glima 38 antigen recognised by autoantibodies in Type I diabetic patients. Diabetologia. 2000 May; 43(5):598-608.
        View in: PubMed
      41. Filvaroff E, Erlebacher A, Ye J, Gitelman SE, Lotz J, Heillman M, Derynck R. Inhibition of TGF-beta receptor signaling in osteoblasts leads to decreased bone remodeling and increased trabecular bone mass. Development. 1999 Oct; 126(19):4267-79.
        View in: PubMed
      42. Perr HA, Ye J, Gitelman SE. Smooth muscle expresses bone morphogenetic protein (Vgr-1/BMP-6) in human fetal intestine. Biol Neonate. 1999 Mar; 75(3):210-4.
        View in: PubMed
      43. Schwitzgebel VM, Gitelman SE. Neonatal hyperinsulinism. Clin Perinatol. 1998 Dec; 25(4):1015-38, viii.
        View in: PubMed
      44. Devoe DJ, Miller WL, Conte FA, Kaplan SL, Grumbach MM, Rosenthal SM, Wilson CB, Gitelman SE. Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab. 1997 Oct; 82(10):3196-202.
        View in: PubMed
      45. Mootha SL, Barkovich AJ, Grumbach MM, Edwards MS, Gitelman SE, Kaplan SL, Conte FA. Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the occult intracranial germinoma in children and adolescents. J Clin Endocrinol Metab. 1997 May; 82(5):1362-7.
        View in: PubMed
      46. Gitelman SE, Kobrin M, Lee A, Fet V, Lyons K, Hogan BL, Derynck R. Structure and sequence of the mouse Bmp6 gene. Mamm Genome. 1997 Mar; 8(3):212-4.
        View in: PubMed
      47. Silverman LA, Gitelman SE. Immunoreactive inhibin, müllerian inhibitory substance, and activin as biochemical markers for juvenile granulosa cell tumors. J Pediatr. 1996 Dec; 129(6):918-21.
        View in: PubMed
      48. Tee MK, Babalola GO, Aza-Blanc P, Speek M, Gitelman SE, Miller WL. A promoter within intron 35 of the human C4A gene initiates abundant adrenal-specific transcription of a 1 kb RNA: location of a cryptic CYP21 promoter element? Hum Mol Genet. 1995 Nov; 4(11):2109-16.
        View in: PubMed
      49. Gitelman SE, Kirk M, Ye JQ, Filvaroff EH, Kahn AJ, Derynck R. Vgr-1/BMP-6 induces osteoblastic differentiation of pluripotential mesenchymal cells. Cell Growth Differ. 1995 Jul; 6(7):827-36.
        View in: PubMed
      50. Erlebacher A, Filvaroff EH, Gitelman SE, Derynck R. Toward a molecular understanding of skeletal development. Cell. 1995 Feb 10; 80(3):371-8.
        View in: PubMed
      51. Gitelman SE, Kobrin MS, Ye JQ, Lopez AR, Lee A, Derynck R. Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo. J Cell Biol. 1994 Sep; 126(6):1595-609.
        View in: PubMed
      52. Bristow J, Tee MK, Gitelman SE, Mellon SH, Miller WL. Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B. J Cell Biol. 1993 Jul; 122(1):265-78.
        View in: PubMed
      53. Bristow J, Gitelman SE, Tee MK, Staels B, Miller WL. Abundant adrenal-specific transcription of the human P450c21A "pseudogene". J Biol Chem. 1993 Jun 15; 268(17):12919-24.
        View in: PubMed
      54. Fries MH, Lebo RV, Schonberg SA, Golabi M, Seltzer WK, Gitelman SE, Golbus MS. Mental retardation locus in Xp21 chromosome microdeletion. Am J Med Genet. 1993 Jun 1; 46(4):363-8.
        View in: PubMed
      55. Saenger P, Lin D, Gitelman SE, Miller WL. Congenital lipoid adrenal hyperplasia--genes for P450scc, side chain cleavage enzyme, are normal. J Steroid Biochem Mol Biol. 1993 Apr; 45(1-3):87-97.
        View in: PubMed
      56. Miller WL, Gitelman SE, Bristow J, Morel Y. Analysis of the duplicated human C4/P450c21/X gene cluster. J Steroid Biochem Mol Biol. 1992 Dec; 43(8):961-71.
        View in: PubMed
      57. Gitelman SE, Bristow J, Miller WL. Mechanism and consequences of the duplication of the human C4/P450c21/gene X locus. Mol Cell Biol. 1992 Jul; 12(7):3313-4.
        View in: PubMed
      58. Gitelman SE, Bristow J, Miller WL. Mechanism and consequences of the duplication of the human C4/P450c21/gene X locus. Mol Cell Biol. 1992 May; 12(5):2124-34.
        View in: PubMed
      59. Lin D, Gitelman SE, Saenger P, Miller WL. Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia. J Clin Invest. 1991 Dec; 88(6):1955-62.
        View in: PubMed
      60. Gitelman SE. Cloning of the LH/CG receptor: implications for a unique G-protein coupled receptor. Trends Endocrinol Metab. 1990 Mar-Apr; 1(4):181-4.
        View in: PubMed
      61. Morel Y, Bristow J, Gitelman SE, Miller WL. Transcript encoded on the opposite strand of the human steroid 21-hydroxylase/complement component C4 gene locus. Proc Natl Acad Sci U S A. 1989 Sep; 86(17):6582-6.
        View in: PubMed
      62. Gitelman SE, Witman GB. Purification of calmodulin from Chlamydomonas: calmodulin occurs in cell bodies and flagella. J Cell Biol. 1980 Dec; 87(3 Pt 1):764-70.
        View in: PubMed
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