Myra A. Lipes, M.D.
Dr. Lipes is an Investigator in the Section on Islet Transplantation and Cell Biology at Joslin and an Assistant Professor of Medicine at Harvard Medical School. She received her medical degree from McGill University in Montreal. After completing her residency training in Pediatrics, she was a medical staff fellow in the Endocrinology Program at the National Institutes of Health. She has been the recipient of the Mary K. Iacocca Faculty Fellowship, a Harcourt General Charitable Foundation New Investigator Award, a Career Development Award from the American Diabetes Association and a Charles H. Hood Foundation Child Health Research Award.
Dr. Lipes' research focuses on understanding the immunological mechanisms underlying type 1 diabetes and on developing strategies for disease prediction and intervention. As a basis for these studies, Dr. Lipes and team use transgenic mouse techniques in non-obese diabetic (NOD) mice, a model for human type 1 diabetes, and more recently, their studies have extended to humans with type 1 diabetes.
To examine the role of the high-risk type 1 diabetes-associated human HLA-DQ8 molecule in the development of diabetes, several transgenic NOD mouse lines were created that expressed different levels of DQ8 proteins but lacked their own immune response genes. Dr. Lipes and colleagues discovered that these “humanized” mice developed not only accelerated diabetes, but also an autoimmune form of heart disease (“myocarditis”), with the appearance of autoantibodies against heart proteins and destructive lymphocytic infiltrates in the heart.
Dr. Lipes and team recently isolated T cell clones directly from the affected hearts and showed that these clones can transfer disease into immunodeficient hosts. These findings raised the possibility that a subset of humans also develop autoimmune heart disease that is mediated by T cells. In collaboration with cardiologists at Brigham and Women’s Hospital, Dr. Lipes and team are testing this hypothesis and recently have developed new screening tests for this purpose.
Other studies focus on the role of cardiac tissue injury in inducing autoimmunity. Patients with type 1 diabetes experience excessive mortality following myocardial infarction, but the reasons for this have been poorly understood. The Lipes laboratory recently discovered that experimental myocardial infarction in NOD mice induces a dramatic post-infarct autoimmunity syndrome with infiltrates in the heart, autoantibody and T cell responses against cardiac antigens. Using its newly developed assays, the Lipes team has promising evidence that a similar response takes place in humans with type 1 diabetes. The results of these studies should open a new window on the pathogenesis of cardiovascular disease complications in type 1 diabetes and could lead to new therapeutic approaches.
A longstanding research interest is in the development of immunoresistant surrogate beta cells for the treatment of type 1 diabetes. These studies arose from the surprising discovery that pituitary cells could be engineered to produce large amounts of insulin, sufficient to cure diabetes when implanted into NOD mice. However, unlike transplanted islets, the insulin-producing pituitary cells evaded immune attack. These findings were unexpected because insulin is a major target of the immune response in type 1 diabetes.
Dr. Lipes and team are studying the molecular mechanisms by which the pituitary cells escape immune attack. If it were possible to engineer these same properties into transplanted islets, this could reduce or eliminate the need for immunosuppressive drug therapy. In parallel studies, the lab has shown that glucose-sensing properties can be introduced into the insulin-producing cells using viral gene delivery vectors and transgenic techniques. The lab is now evaluating the glucose-sensing capabilities and therapeutic potential of these bioengineered cells.
Medarova Z, Bonner-Weir S, Lipes MA, Moore A. Imaging b-cell death with a near-infrared probe. Diabetes 54:1780-1788, 2005.
Jaeckel E, Lipes MA, von Boehmer H. Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes. Nat Immunol 5:1028-1035, 2004.
Havari E, Lennon-Dumenil AM, Klein L, Neely D, Taylor JA, McInerney MF, Wucherpfennig KW, Lipes MA. Expression of the B7.1 costimulatory molecule on pancreatic b cells abrogates the requirement for CD4 T cells in the development of type 1 diabetes. J Immunol 173:787-796, 2004.
Taylor JA, Havari E, McInerney MF, Bronson RT, Wucherpfennig KW, Lipes MA. A spontaneous model for myocarditis using the human MHC molecule HLA-DQ8. J Immunol 172:2651-2658, 2004.
Faradji RN, Havari E, Chen Q, Gray J, Tornheim K, Corkey BE, Mulligan RC, Lipes MA. Glucose-induced toxicity in insulin-producing pituitary cells that coexpress GLUT2 and glucokinase: implications for metabolic engineering. J Biol Chem 276:36695-36702, 2001.
Page last updated: September 20, 2014