Tihamer Orban, M.D.
Dr. Orban is an Associate Investigator in the Section on Immunobiology at Joslin and an Instructor in Medicine at Harvard Medical School. He received his medical degree and board certification in Pediatrics from Medical School Szent-Gyorgyi Albert University Hungary. He is a member of the Endocrine Society, U.S.A., and of the Royal College of Paediatrics and Child Health, London, England.
Since coming to Joslin in 1993, Dr. Orban has been working to predict, prevent and monitor type 1 diabetes, which often develops over the course of several years before becoming clinically apparent. Recognizing the benefits of earlier diagnosis and treatment of patients at risk, Dr. Orban established humoral markers (found in blood serum) to: (1) identify at-risk people appropriate for prevention or intervention trials, and (2) understand how aggressively the disease may manifest in each person. To test these markers, Dr. Orban implemented assays, now used throughout the country. He also collaborated with investigators in other institutions to find other novel cellular and humoral markers for type 1 diabetes.
Dr. Orban is one of the Principal Investigators in three major networks—TrialNet, Immune Tolerance Network (ITN) and Autoimmune Center of Excellence (ACE)—that are funded by the National Institutes of Health (NIH) and dedicated to translating basic research into wider clinical application for the prediction, prevention and intervention of type 1 diabetes autoimmunity.
The ITN is currently funding a clinical trial that tests a novel antigen-based vaccination, developed by Dr. Orban, for type 1 diabetes. The therapy, which he pioneered for human use, aims to stop the immune system from attacking the body’s own insulin-producing beta cells by re-establishing self-tolerance. This clinical trial is now in phase 1 at Joslin and Children’s Hospital Boston and it is near completionSeveral patients in early stages of disease have been vaccinated, and no problems with side effects or with the patients’ overall response to the vaccine have been observed. The ITN is currently working on moving this novel antigen-based vaccination to a phase 2 clinical trial.
Since humoral markers already have contributed to an understanding of type 1 diabetes and the autoimmune process, Dr. Orban believes research can now focus on a better understanding of human T cells—the real culprits in autoimmunity. According to Dr. Orban, T cells hold the key to solving problems in the immune system and developing the most effective interventions to treat this devastating disease in children and young adults.
It is important to translate the data collected from animal models to the prediction and prevention of type 1 diabetes in people. In future work, Dr. Orban plans to use these data to design new clinical trials for patients with type 1 diabetes autoimmunity. He is encouraged that the NIH has funded three networks dedicated to translational science and plans to work closely with them to conduct research “with the patient and for the patient.”
Viglietta V, Kent SC, Orban T, Hafler DA. GAD65-reactive T cells are activated in patients with autoimmune type 1a diabetes. J Clin Invest 109:895-903, 2002.
Orban T, Landaker E, Ruan Z, Cordeman TP, Weitgasser R, Bonner-Weir S, Jackson RA, Patti ME. High-fructose diet preserves beta-cell mass and prevents diabetes in nonobese diabetic mice: a potential role for increased insulin receptor substrate-2 expression. Metabolism 50:1369-1376, 2001.
Orban T, Kent S, Malik P, Milner JD, Schuster K, Jackson RA, Hafler DA. Heterophile antibodies indicate progression of autoimmunity in human type 1 diabetes mellitus before clinical onset. Autoimmunity 34:247-264, 2001.
Malecki MT, Jhala US, Antonellis A, Fields L, Doria A, Orban T, Saad M, Warram JH, Montminy M, Krolewski AS. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet 23:323-328, 1999.
Wilson SB, Kent SC, Patton KT, Orban T, Jackson RA, Exley M, Porcelli S, Schatz DA, Atkinson MA, Balk SP, Strominger JL, Hafler DA. Extreme Th1 bias of invariant Va24JaQ T cells. Nature 391:177-181, 1998.