Dr. Robert Intine – Rosalind Franklin University
Dr. Intine’s lab focuses on identifying the molecular mechanisms that cause the persistence and progression of diabetic complications, a phenomena termed metabolic memory. To this end, his lab has developed a zebrafish model of diabetes mellitus which exhibit metabolic memory following reversion to normal glycemia after pancreas regeneration. This provides a unique opportunity to study metabolic memory in the context of a true restoration of the normal glycemic state similar to what would be seen with human patients after transplantation. Dr. Intine intends to perform genome wide expression analysis to reveal the molecular pathways altered by metabolic memory as a foundation for the identification of therapeutic targets.
Dr. Boris Musset – Rush University Medical Center
Reactive oxygen species (ROS) are implicated in several diabetes-related diseases. They are involved in cell signaling, cell respiration and bacterial killing. During overproduction, they can cause severe damage of the body’s own cells. Dr. Musset has found that ROS production by human monocytes is strongly dependent on blood sugar concentrations. In diabetic patients the blood sugar concentration can change dramatically. The connection of blood sugar levels and ROS might be one of the reasons why diabetic patients develop more fatal progression of vascular diseases. He is investigating the biophysical mechanisms underlying this process.
Dr. Defu Zeng, M.D – Beckman Research Institute
Patients with refractory late-stage type 1 diabetes (T1D) are unable to control their glucose levels using insulin injections. Currently, the only effective therapy for such patients is islet transplantation. However, under the current protocol of immunosuppressants for prevention of rejection, the insulin-independence of the patients after islet transplantation only lasts an average of 3-5 years, due to the chronic rejection of the islet grafts. Dr. Zeng’s laboratory at City of Hope is developing a new novel treatment for refractory late-stage T1D in a mouse model, which involves a combination of non-toxic hematopoietic cell transplantation (HCT) and administration of growth factors including epidermal growth factor (EGF), gastrin, and/or exendin-4. Their preliminary data have shown that this combination therapy can reverse late-stage T1D in mice. They are now expanding the studies and exploring the mechanisms how the novel therapy leads to beta cell regeneration. This line of research may result in the development of a curative therapy for late-stage T1D and make islet transplantation procedure obsolete.
Dr. David Gracias – Johns Hopkins University
Dr. Gracias proposes to use lithographic processes that have revolutionized the microelectronics industry to precisely structure a three dimensional bio-artificial pancreas from the nano to the macro scale. This precision is combined with novel self-assembly and molecular surface modification methods to create a device that facilitates adequate diffusion to transplanted islet cells while also enabling immunoisolation.
Dr. Mina Peshavaria – University of Vermont
Dr. Peshavaria proposes to use genetic mouse models to test the role of AMP Kinase and mTOR signaling pathway in growth, proliferation and survival of pancreatic beta cells when levels of the classical insulin signaling pathway intermediates are reduced.
Dr. Jerry Nadler – Eastern Virginia Medical School
Dr. Nadler has identified two different drugs that together can reverse T1DM in diabetic non-obese diabetic (NOD) model, Lisofylline (LSF) and Exendin-4. Each drug acts in different ways to restore functional insulin secretion. LSF reduces a specific factor that leads to autoimmune damage while Exendin-4 helps insulin cells grow and function better. Both drugs have been used in clinical trials but never together or for this use. This study proposes to perform a short-term pilot study using Lisofylline alone and in combination with Exendin-4 in subjects with T1DM. The proposed plan is to obtain the necessary biomarker, blood levels and safety data that will then allow us to move forward and plan a major phase 2 multi-center study to fully evaluate efficacy of this novel combination treatment to restore insulin secretion in people with T1DM.
Dr. James L. Sherley – Boston Biomedical Research Institute
Dr. Sherley’s team of scientists in the Adult Stem Cell Technology Center at Boston Biomedical Research Institute recently developed a method for expanding adult human pancreatic stem cells in culture. The expanded stem cells produce differentiated progeny cells with both alpha-cell and beta-cell properties, indicating potential to produce pancreatic islets after transplantation into the body. Dr. Sherley’s team will work to adapt the expansion of the new stem cells to defined culture media that are suitable for future clinical evaluations; and they are currently working to engage clinical partners for this purpose. A major focus of the research will also be evaluation of the properties of the cells after transplantation into experimental mouse models and continued bioengineering of the cells to enhance their transplantability and pancreatic functions.
Dr. Denise Faustman – Massachusetts General Hospital
Dr. Faustman is leading the human clinical trial program at Massachusetts General Hospital (MGH) testing Bacillus Calmette-Guérin (BCG), an inexpensive generic drug, as a treatment for advanced type 1 diabetes. In the recently completed Phase I study, BCG was administered to adults who had been living with type 1 diabetes for an average of 15 years. This treatment not only helped eliminate the defective T cells that mistakenly attack and destroy the insulin-producing cells of the pancreas, it also temporarily restored the ability of the pancreas to produce small amounts of insulin. The next step, a Phase II human study, is currently being planned, with the goal of identifying a drug dose and schedule that will put advanced type 1 diabetes into remission for longer time periods and to greater degrees in the hope it will change complications and blood sugar control.
