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Shawn Eck

Peter Engelmann, PhD

Pavol Fabian

Klara Farkas, M.D. Ph.D

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Janos Kis, M.D.

Lisa Kuhn, RN

Hui Li

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Patryk Moskwa, M.D. Ph.D

Derek Peterson

Irene Reske

Geoffrey Richman

Zheng Ruan

Susan Sweatt, RN

Laszlo Szereday, M.D.

Andras Treszl, M.D.

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Tihamer Orban, M.D.

Investigator

Joslin Diabetes Center

10/1/1993 -

More details.....

Tihamer Orban, M.D.
torban@joslin.harvard.edu

Since arriving at Joslin in 1993, Tihamer Orban, M.D., has been working to predict, prevent and monitor type 1 diabetes, which often develops over the course of several years before it becomes clinically apparent. Recognizing the benefits of earlier diagnosis and treatment of patients at risk, Dr. Orban established humoral markers — found in the serum of the blood — both to identify people at risk for prevention/ intervention trials and to understand how aggressively the disease will be manifested clinically in each person. To test these markers, Dr. Orban implemented assays that are now in wide use around the country. To find additional novel cellular and humoral markers for type 1 diabetes, Dr. Orban has collaborated with investigators in other institutions.

Dr. Orban is one of the Principal Investigators in three major NIH-funded networks—TrialNet; Immune Tolerance Network (ITN); and Autoimmune Center of Excellence (ACE)—that are dedicated to translating basic research into wider clinical applications for type 1 diabetes autoimmunity prediction, prevention and intervention.

Visit the TrialNet Website for more information: www.DiabetesTrialnet.org

The ITN is currently funding a clinical trial which tests a novel antigen-based vaccination for autoimmune type 1 diabetes developed by Dr. Orban. This therapy—which Dr. Orban has 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 FDA-approved clinical trial is now in Phase I at Joslin and Children’s Hospital Boston. Several patients in early stages of disease have been vaccinated and the results are encouraging: monitoring of insulin production and the immune system have revealed no problems with side effects or the patients’ overall response to the vaccine.

See the ITN Website for more information specific to Dr. Orban's clinical trial: Immune Tolerance Network

It is Dr. Orban’s belief that since humoral markers have contributed to an understanding of type 1 diabetes and the autoimmune process, the research focus can now move to a better understanding of human T cells. He considers T cells the “culprits” that hold the key to solving problems in the immune system in case of autoimmunity and providing direction for the development of the most effective interventions to treat this devastating disease in children and young adults.

In future work, Dr. Orban plans to expand human clinical trials. It is important to translate the large amount of data already collected from animal models to the prediction and prevention of type 1 diabetes in humans. In addition, these data should be used to design new interventional clinical trials in 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.”

Biographic Sketch:

Dr. Orban is an Instructor in Medicine at Harvard Medical School and an Associate Investigator in the Section of Immunology and Immunogenetics at Joslin Diabetes Center. 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 a member of the Royal College of Paediatrics and Child Health, London, UK.

Selected References:

Wilson B, Kent S, Patton T, Orban T, Exley M, Porcelli S, Balk S, Jackson R, Strominger J, Hafler D. In human autoimmune diabetes there is an extreme Th1 bias of invariant V alpha J alpha Q T-cells. Nature 391:177-181,1998.

Malecki MT, Jhala US, Antonellis A, Fields L, Doria A, Orban T, Saad M, Warram J, Montminy M and Krolewski A. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet 23:323, 1999.

Orban T, Kent S, Malik P, Milner J, Schuster K, Jackson R, and Hafler D. Heterophile antibodies indicate progression of autoimmunity in human Type 1 diabetes mellitus before clinical onset. Autoimmunity 34: 247-264, 2001.

Orban T, Landaker E, Ruan Z, Cordeman T, Weitgasser R, Bonner-Weir S, Jackson R, Patti ME. High fructose diet preserves b-cell mass and prevents diabetes in NOD mice: a potential role for increased IRS-2 expression. Metabolism 50:1369-1376, 2001.

Viglietta V, Kent S, Orban T, Hafler D, GAD65-reactive T-cells are activated in patients with autoimmune type 1a diabetes. J Clin Invest 109:895-903, 2002.