Welcome to the Hampe Laboratory
The Hampe laboratory focuses on the understanding of human autoimmune diseases with the long-term goal to develop therapies aimed at their cure and prevention. Particular areas of research are autoimmune diabetes and Stiff Person Syndrome. Both diseases are autoimmune-mediated and are characterized by the presence of autoantibodies directed to the 65kDa isoform of glutamate decarboxylase (GAD65Ab). GAD65 is one of two enzymes that catalyze the formation of the inhibitory neurotransmitter GABA. It is primarily expressed in the central nervous system and in the insulin-producing beta cells of the pancreas. While its role in neurotransmission is well understood, its function in the pancreatic beta cells remains an enigma.
GAD65Ab in autoimmune diabetes. Conformational epitopes: GAD65Ab in autoimmune diabetes are dependent on the conformational integrity of the antigen. Traditional epitope mapping assays using deletion mutation, fusion proteins etc often compromise the conformation and lead to biased results. We developed a novel epitope mapping assay that depends on competition of the serum antibodies with recombinant Fab derived from GAD65-specific monoclonal antibodies. Using this novel technique, we identified disease-specific GAD65Ab epitopes. We also succeeded to detect antibody maturation towards these epitopes during progression of disease. Anti-idiotypic antibodies Recently we identified the presence of anti-idiotypic antibodies directed against GAD65Ab in the majority of healthy individuals. Anti-idiotypic antibodies have been described as a regulatory element in the humoral immune response. Importantly anti-idiotypic antibody titers are elevated during remission in patients with autoimmune disease. Currently we investigate the role of anti-idiotypic antibodies in the disease pathogenesis both in humans and in animal models for type 1 diabetes.
GAD65Ab in Stiff Person Syndrome. A pathogenic role GAD65Ab in Stiff Person Syndrome and other GAD65Ab-associated movement disorders has been suggested based on the finding that GAD65Ab in this disease inhibit the enzymatic activity of GAD65 and that SPS patients have decreased levels of GABA. Rats that are intracerebellar injected with GAD65Ab show significant changes in their neurophysiology and their behavior. These findings strongly support a pathogenic role of GAD65Ab in the pathogenesis. Currently we are developing an animal model for Stiff Person Syndrome and Cerebellar Ataxia to investigate the natural history of GAD65Ab in these diseases. The research is currently funded through the National Institutes of Health and the United States – Israel Binational Science Foundation.
Larsson HE, Jönsson I, Lernmark A, Ivarsson S, Radtke JR, Hampe CS; Diabetes Prediction in Skåne (DiPiS); Type 1 Diabetes Trial Network. Decline in titers of anti-idiotypic antibodies specific to autoantibodies to GAD65 (GAD65Ab) precedes development of GAD65Ab and type 1 diabetes. PLoS One. 8:e65173, 2013.
Oak S, Gaur LK, Radtke J, Patel R, Iyer D, Ram N, Gaba R, Balasubramanyam A, Hampe CS. Masked and Overt Autoantibodies Specific to the DPD Epitope of 65-kDa Glutamate Decarboxylase (GAD65-DPD) Are Associated With Preserved β-Cell Functional Reserve in Ketosis-Prone Diabetes. J Clin Endocrinol Metab. E1040-1044, 2014.
Current and Recent Members of the Hampe Laboratory
Chris Hampe received her PhD at the Weizmann Institute of Science in Israel in 1997. She did her post-doctoral training in Dr. Åke Lernmark’s laboratory at the University of Washington, Seattle and is currently a Research Associate Professor at the Diabetes and Obesity Center of Excellence at the University of Washington.. Xin Wang received his MD at Nanjing Medical University, China in 2001 and his PhD at Nanjing Medical University, China in 2007. He is currently a visiting scholar at Dr. Hampe’s laboratory. Jared Radtke received his BA from Ohio Wesleyan University in 2003. He is currently a Research Scientist.
Diabetes and Obesity Center of Excellence
University of Washington School of Medicine
South Lake Union Campus
850 Republican Street Rm S230
Seattle, WA 98109-8055
Fax: (206) 543-3567
Christiane Hampe: (206) 221-5275
Lab: (206) 616-0148
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