Type 1 diabetes is a complicated, complex disease. Conquering this multi-faceted condition requires people working from all angles. At Joslin Diabetes Center, researchers are up to the task.
In type 1 diabetes, the immune system mistakenly attacks the pancreas. Many research teams at Joslin are working to better understand this complex autoimmune process, including scientists in the Human Immunology Program Project (HIPP).
Stephan Kissler, Ph.D. studies the genes involved in type 1 diabetes, which are spread over more than 50 genomic regions. But little is known about specific gene variants and how they impact the immune system. His goal is to uncover key defects in immune regulation that could be targeted to treat or cure type 1 diabetes.
Myra Lipes, MD, recently discovered that when people with type 1 diabetes suffer a heart attack, they have a greater chance of developing further heart damage, caused by factors triggering an autoimmune response against cardiac muscle tissue. Her research is focused on how to selectively stop this detrimental response.
Jason Gaglia, MD, MMSc, is harnessing the power of magnetic nanoparticle-enhanced magnetic resonance imaging (MNP-MRI) to visualize changes in the pancreas. This technique holds tremendous promise for studying the disease process and the effect of new diabetes treatments.
Thomas Serwold, PhD, focuses on how immune cells called T cells develop in the thymus, where they learn to tolerate the body’s own cells. But if this process is imperfect, “bad” T cells may survive. His lab is investigating how to detect and trap destructive T cells before they can attack pancreatic beta cells. Dr. Serwold is also using stem cell technology to regenerate the “good” T-cells and re-educate the “bad” T-cells.
Aldo Rossini MD is the senior advisor of HIPP. During his research career, he has studied the mechanisms involved in loss of immune tolerance that occurs in type 1 diabetes and strategies to reestablish immune tolerance to prevent the disease.
The immune system attacks and destroys beta cells, leaving people with type 1 diabetes without a supply of insulin. Curing the disease will need to consist of a new supply of the insulin-secreting beta cells. Researchers at Joslin are figuring out exactly how beta cells work, how they die, and how they can be replenished.
Rohit Kulkarni, M.D., Ph.D., studies the role of insulin and insulin growth factor in glucose sensing in beta cells, protection against cell death and in regulating which genes get turned on when in islet cells. He is also looking into creating new beta cells by turning adult cells into stem cells, which can then become β (beta) cells. Dr. Kulkarni has also discovered a new growth factor from the liver that can induce the beta cell to grow.
Gordon Weir, M.D., tries to understand what happens to beta cells in type 1 diabetes by studying normally functioning beta cells. He also wants to improve beta cell transplantation by finding new sources of beta cells, perfecting existing transplant procedures, and figuring out how to protect the newly transplanted beta cells from autoimmune attack. To this last point, he is collaborating with Dr. Robert Langer at MIT to develop materials which can encapsulate beta cells. This device could release insulin and hopefully will not induce inflammatory immune responses from the host.
Susan Bonner-Weir, Ph.D., aims to elucidate the process by which the pancreas and its constituent islets grow and develop in order to find new sources of beta cells. She has found evidence suggesting the ductal cells, also found in the pancreas, could become functional beta cells.
Peng Yi, M.D., discovered betatrophin, a hormone that stimulates the production of beta cells while in Dr. Doug Melton’s lab. He hopes that by understanding how this hormone functions, he will be able to create a treatment to induce beta cell proliferation in people with type 1 diabetes.
Arun Sharma, Ph.D., investigates the process by which beta cells grow, mature and eventually secrete insulin. He focuses on the role of MafA in beta cell development. MafA is a protein that helps beta-cell-precursors become glucose-responsive, insulin-secreting cells.
TECHNOLOGY AND CLINICAL STUDIES
While a cure is in the works, type 1 diabetes needs the best treatments. A number of researchers at Joslin focus on how to make living life with diabetes as manageable as possible.
Howard Wolpert, M.D., works with diabetes technology, such as insulin pumps and continuous glucose monitors. Dr. Wolpert’s research uses such technology to study things like nutrients’ roles in type 1 diabetes management.
Lori Laffel, M.D., M.P.H., is the Chief of the Pediatric, Adolescent and Young Adult Section. She studies how family involvement and external support, such as the Joslin “Care Ambassador” model, increases the likelihood that children will continue good diabetes care during late adolescence. She also works to understand the importance of technology in diabetes management for children, including continuous glucose monitors and wireless communication devices.
To help patients, basic research needs to make its way into treatments. Translational research allows scientists to take discoveries from the bench to the bedside.
George King, M.D., is the Chief Scientific Officer. He has been leading the Medalist Study for the last 7 years. The Medalist Study is focused on a group of type 1 diabetic patients numbering 1000 who have had diabetes for 50 years or longer. The goal of the study is to identify protective factors for the eye and kidney which could prevent these complications even in the presence of hyperglycemia. In addition, the Medalist Study has opened the doors to the idea that regeneration of the beta cell could be a treatment for a majority of people with chronic type 1 diabetes.
Andrzej Krolewski, M.D., Ph.D., has been studying diabetic nephropathy or kidney disease in type 1 diabetic patients for over 30 years. His recent work has shown potential biomarkers for early stages of diabetic kidney disease. This is critical in order to intervene and prevent the development of kidney disease in 30 to 40 percent of type 1 diabetic patients.
Alessandro Doria, M.D., Ph.D., M.P.H., has been focused on genetics of diabetes. His recent work which is funded by NIH at $24.3 million to test the treatment with allopurinol, a generic drug, to lower uric acid, can prevent the progression of diabetic kidney disease in patients with type 1 diabetes.