Head: TBD,

Mechanisms of and Therapies for Type-1 Diabetes

The major goal of these laboratories is to elucidate the immunological mechanisms underlying type 1 diabetes mellitus and to exploit the resultant knowledge to develop novel disease therapies. The NOD mouse model, which spontaneously develops an autoimmune disease strikingly similar to human type 1 diabetes, is employed to investigate the immunology and genetics of leukocyte invasion into the pancreatic islets and the
consequent destruction of b cells. Engineered mouse models are also used extensively to highlight particular facets of pathophysiology. Studies on diabetes patients are aimed at developing methods to permit better prediction of disease initiation as well as more accurate monitoring of its progression or reversal. The genetics of human diabetes is also studied to aid dissection of disease mechanisms. A certain number of pilot clinical trials to prevent, halt or monitor type 1 diabetes are currently in progress. This section’s efforts constitute a broad bench-to-bedside-back-to-bench approach, and exploits a number of cutting-edge technologies. Genetics, genomics, proteomics, bioinformatics, imaging, immunomodulation, siRNAs, gene-targeted mice, CHIPs, Treg cells, yeast two-hybrids, lentigenics, clinical trials are all part of its working vocabulary.


Jackson Lab:

Richard Jackson splits his time between the Research, Clinic and Strategic Initiatives Divisions. For many years, his research efforts have focused on devising strategies to prevent type 1 diabetes. One necessary step towards this goal is to more accurately identify individuals at risk of developing diabetes, and Dr. Jackson was an important contributor to seminal work on autoAb markers. At present, his primary research activity is to head an NIH-funded clinical trial that attempts to translate to humans a non-invasive method for imaging pancreas inflammation first developed in mouse models (see above). This approach relies on preferential extravasation of the MRI probe “Combidex” at sites of inflammation (see Fig). If successful, this imaging procedure will be extremely valuable in aiding complex diagnoses, monitoring disease course, and evaluating diabetes reversal after therapeutic intervention, in particular the last application.


Orban Lab:

Tihamer Orban’s efforts have been directed at predicting, preventing and monitoring type 1 diabetes. Dr. Orban is a participating PI in two major NIH-funded diabetes trial networks — TrialNet and the Immune Tolerance Network (ITN). Currently, his major research activity is a Phase I clinical trial that tests a novel antigen-based vaccination strategy: insulin B chain in Incomplete Freund’s Adjuvant. His group is also studying the behavior of peripheral-blood NK-T cell populations through diabetes progression, with the aim of identifying novel biomarkers.


Five recent “highpoints”: