Dr. Gaglia is a physician scientist; many of his research projects are inspired by questions raised in the clinic, with type 1 diabetes being a major focus. He is developing clinically applicable techniques to monitor insulitis (the destructive process that leads to type 1 diabetes), peripheral markers of diabetes related autoimmunity, and measures of the insulin-producing pancreatic beta cells themselves. In collaboration with other investigators, Dr. Gaglia is applying these techniques to learn more about the underlying processes that lead to type 1 diabetes as well as developing novel treatment strategies for this disease.

Monitoring inflammation in the pancreas via magnetic nanoparticle enhanced magnetic resonance imaging:

Type 1 diabetes results from autoimmune destruction of the pancreatic beta cells. Although there are many animal models of diabetes, due to the inaccessibility of the pancreas, it has been very difficult to study this process in humans. Teamed with Drs. Diane Mathis and Christophe Benoist at Harvard Medical School and Dr. Ralph Weissleder at Massachusetts General Hospital, Dr. Gaglia has been using magnetic nanoparticle enhanced magnetic resonance imaging (MNP-MRI) to visualize changes in the pancreas associated with the inflammatory infiltrate that can cause type 1 diabetes. This new technique has great promise in bettering our understanding of type 1 diabetes and facilitating development of immunomodulatory therapies for this disease.

Measurement of beta cell mass:

Insulin is produced by the pancreatic beta cells and inadequate insulin production leads to diabetes. Unfortunately, it has been difficult to accurately measure the small fraction of the pancreas that is made up of beta cells. Dr. Gaglia has been collaborating with investigators at Joslin, Harvard Medical School, and Massachusetts General Hospital to develop new probes for imaging beta-cell mass. Several such probes targeting the GLP-1 receptor on beta cells are showing promise in animal models of diabetes. It is hoped that this approach will be translatable to a clinically applicable imaging strategy.

Reprogramming pancreatic exocrine cells to become insulin producing beta cells:

 This project builds upon prior work by Drs. Douglas Melton, Qiao Zhou, and Gordon Weir to reprogram exocrine pancreas cells into insulin producing cells using the transcription factors PDX-1, Ngn3, and MafA. In collaboration with Drs. Zhou and Weir, Dr. Gaglia is working to overcome many of the barriers to clinical implementation of such a strategy. Specifically, a more immune friendly delivery method is being developed and the immune responses of animals with pre-existing type 1 diabetes are being studied.

Monitoring autoimmunity in diabetes:

 Currently, islet-antigen-targeted autoantibody tests are used as a peripheral marker of the autoimmunity that leads to type 1 diabetes. However, these autoantibodies are immunologically distant from the destructive processes that cause diabetes. Using MNP-MRI as a noninvasive gold-standard, Dr. Gaglia’s lab is developing new peripheral assays of autoimmunity in diabetes. 

Clinical trials in type 1 diabetes:

 As described above, Dr. Gaglia is leading a clinical trial to further develop MNP-MRI for noninvasively monitoring diabetes at the level of the pancreas. He is also working with additional investigators to bring this technique to other type 1 diabetes clinical trials.