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Regenerative Therapies for Diabetes - Ezio Bonifacio

Type I diabetes is characterized by insulin deficiency primarily caused by the autoimmune-mediated destruction of insulin secreting beta cells located in the pancreas.
Understanding how the autoimmunity initiates and is perpetuated is relevant to introducing therapies that will prevent beta cell destructive immunity.

Previous and current research

The pathogenesis of diabetes mellitus hinges on the loss of pancreatic islet beta cells which in type 1 diabetes is mediated by autoimmunity. We have studied how autoimmunity develops in the course of the disease in children, the target beta cell antigens and epitopes, and the factors that predispose to autoimmunity. We discovered that autoimmunity develops most frequently around 1 to 2 years of age and that the proinsulin prohormone is the primary target antigen. more

Future projects and goals

  • Identify the mechanisms of autoreactive T effector and T regulatory expansion in man that can be harnessed to maintain or re-instate self-immune tolerance.
  • Markers of autoimmunity for the early identification of infants and children who will develop type 1 diabetes.
  • Clinical primary antigen-specific prevention trials in genetically susceptible infants.
  • Establish a newborn testing and primary prevention program.

Selected publications

Heninger A-K, Eugster A, Kuehn D, Buettner F, Kuhn M, Lindner A, Dietz S, Jergens S, WIlhelm C, Beyerlein A, Ziegler A-G, Bonifacio E. A divergent population of autoantigen-responsive CD4+ T cells in infants prior to β cell autoimmunity. Science Translational Medicine. 2017; 378 (9)

Bonifacio E, Ziegler A-G, Klingensmith G, Schober E, Bingley PJ, Rottenkolber M, Theil A, Eugster A, Puff R, Peplow C, Buettner F, Lange K, Eisenbarth G, Hasford J, Achenbach P. Effects of high dose oral insulin on immune responses in children at high risk for type 1 diabetes: the Pre-POINT randomized clinical trial. JAMA 2015; 313(15):1541-9

Bonifacio E. Predicting type 1 diabetes using biomarkers. Diabetes Care 2015;38(6):989-96

Eugster A, Lindner A, Catani M, Heninger AK, Dahl A, Klemroth S, Kühn D, Dietz S, Bickle M, Ziegler AG, Bonifacio E. High Diversity in the TCR Repertoire of GAD65 Autoantigen-Specific Human CD4+ T Cells. J Immunol. 2015; 194(6):2531-8

Ziegler AG, Rewers M, Simell O, Simell T, Lempainen J, Steck A, Winkler C, Ilonen J, Veijola R, Knip M, Bonifacio E, Eisenbarth GS. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013;309(23):2473-9

Heninger AK, Monti P, Wilhelm C, Schwaiger P, Kuehn D, Ziegler AG, Bonifacio E. Activation of islet autoreactive naïve T cells in infants is influenced by homeostatic mechanisms and antigen presenting capacity. Diabetes 2013; 62(6):2059-66

Eugster_et_al._2015_TCR_sequences.xlsx

Contact

Group Leader

Prof. Ezio Bonifacio, PhD
ezio.bonifacio[at]crt-dresden.de

Assistant to Group Leader

Lydia Ventola
lydia.ventola[at]crt-dresden.de
Phone: +49 (0)351 458 82101

Lab Activities

Master Course Regerative Biology and Medicine

  • Reg. Biology and Medicine Cell- and Organ-based Research
  • Reg. Biology and Medicine Scientific Working Methods and Conduct
  • Reg. Biology and Medicine Organ Systems and Disease

Funding