Joslin Investigator Details

A Harvard Medical School Affiliate

Welcome to the Joslin Research Website


	Joslin Investigator:

Myra Lipes, M.D.

Investigator Specifics:

Professional Details:

CV not available

Member of Section:

Current Fellows, Students, or Lab Members:

Lisbeth Cornivelli

Raju Gottumukkala, Ph.D.

Panagiota Stamou, Ph.D.

Past Fellows, etc.:

Edward Boschetti

Yanyan Hao

Evis Havari

Tao Li

Devon Neely

Muhammad Tani Tabiin

Heather Thomas

Investigators

Adjunct Investigators

Fellows & Team Members

DERC Cores

Research Sections

Joslin Resources

Myra Lipes, M.D.

Investigator

Joslin Diabetes Center

DERC Core Director: Transgenics Mouse Facility

Joslin Diabetes Center

9/1/1987 -

The laboratory of Myra Lipes, M.D., is focused on investigating the cellular and molecular events that initiate beta cell autoimmunity, and on developing genetic strategies to prevent and treat type 1 diabetes.

A number of different transgenic and knockout NOD mouse model systems have been created in her lab for these purposes. For example, insulin has been shown to be a major autoantigen in humans and in NOD mice. It was therefore predicted that recurrent autoimmunity might be a barrier to the transplantation of non-islet cells that were genetically engineered to produce insulin. To examine whether insulin-producing non-islet cells would by targeted by the autoimmune cascade that destroys beta cells, the Lipes lab created transgenic NOD mice that produced insulin in the pituitary. These studies showed that the pituitary cells from the transgenic mice produced abundant amounts of insulin, similar to the islet beta cells. Surprisingly, however, unlike insulin-producing beta cells, the insulin-producing pituitary cells were protected against autoimmune destruction, including by insulin-specific T-cell clones that rapidly destroyed the islet beta cells.

The ability of the pituitary cells to produce large amounts of insulin, along with their ability to elude attack by cells of the immune system, suggested that these cells might be used to treat type 1 diabetes. Remarkably, transplantation of small amounts of these insulin-producing cells cured diabetes in NOD mice. In view of these results, the Lipes lab is now using viral gene delivery systems and transgenic mouse techniques to bioengineer into these pituitary cells the capability to secrete insulin in response to glucose and meals. These steps could create a source of artificial beta cells that could be used to treat type 1 diabetes.

Other studies in the Lipes Lab are focused on understanding the mechanism whereby immune response genes predispose to the development of type 1 diabetes. The primary gene for diabetes susceptibility in both humans and NOD mice is located within the class II major histocompatibility complex (MHC) region. The Lipes lab has recently created transgenic NOD mice in which their own class II MHC genes were removed by gene targeting techniques, and replaced with the human DQ8 gene, DQA1*0301/DQB1*0302, which confers the highest risk for developing diabetes in humans. These "humanized" mice will be used to determine how these key immune response genes function in the development of diabetes. These mice will also be used to test whether diabetes in these mice can be prevented with synthetic DQ8 blockers that are being developed by collaborators at Harvard University.

Selected References:

Lipes, M.A., Rosenzweig, A., Tan, K-N., Tanigawa, G., Ladd, D., Seidman, J.G., Eisenbarth, G.S., Progression to Diabetes in Nonobese Diabetic (NOD) Mice with Transgenic T Cell Receptors, Science, 1993, 259: 1165-1169.

Araki, E., Lipes, M.A., Patti, M.E., Bruning, J.C., Haag, B., Johnson, R.S., Kahn, C.R., Alternative Pathway of Insulin Signaling in Mice with Targeted Disruption of the IRS-1 Gene, Nature, 1994, 372: 186-190.

Lipes, M.A., Cooper, E.M., Skelly, R., Rhodes, C.J., Boschetti, E., Weir, G.C., Davalli, A.M., Insulin-secreting Non-islet Cells Are Resistant to Automimmune Destruction, Proc. Natl. Acad. Sci, USA, 1996, 93: 8595-8600.

Lipes, M.A., Davalli, A.M., and Cooper, E.M., Engineering Insulin Expression in Non-Islet Cells: Implications for Beta-cell Replacement Therapy for IDDM, Acta Diabetologica, 1997, 34: 2-5.

Faradji R, Havari E, Chen Q, Gray J, Tornheim K, Corkey B, Mulligan RC, Lipes MA: Glucose-induced toxicity in insulin-producing pituitary cells coexpressing GLUT2 and glucokinase: Implications for metabolic engineering. J. Biol. Chem. 2001; 276: 36695-36702.

Moore A, Sun Z, Corey D, Hoegemann D, Weissleder R, Lipes MA: MRI of insulitis in autoimmune diabetes. Magn Reson Med 2002; 47: 751-758.

Wolpert HA, Faradji RN, Parent R, Bonner-Weir S, Lipes MA: Metabolic decompensation in pump users due to lyspro insulin precipitation. British Medical Journal 2002; 324: 1253.

Biographical Sketch:

Dr. Lipes is an Investigator in the Section on Immunology and Immunogenetics at Joslin and Assistant Professor of Medicine at Harvard Medical School. She is also Director of the Transgenic Mouse Care Facility at the Joslin. 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 NIH and a Research Associate in the Cell Biology and Metabolism Branch of the National Institutes of Child Health and Human Development at NIH. She has been the recipient of the Mary K. Iacocca 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.