Christiane Hampe, PhD

Background:

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.

Focus:

Dr. Hampe's research interests center on human autoimmune diseases and the role of autoantibodies in disease pathogenesis with particular interest in Type 1 diabetes and Stiff Person Syndrome.  More specifically, areas of focus are as follows.

Identification of autoantibodies and their epitopes in different forms of diabetes, and during progression to type 1 diabetes
The major autoantibodies in type 1 diabetes are defined as being specific to insulin (IAA), the tyrosine-phosphatase-like protein IA-2 (IA2Ab), and the 65kDa isoform of glutamate decarboxylase (GAD65Ab). GAD65Ab in type 1 diabetes are especially 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 were able to identify disease-specific GAD65Ab epitopes. We also succeeded to detect antibody maturation towards these epitopes during progression of disease.

The studies encompass the following areas:
• Characterization of the molecular aspects autoantigen-autoantibody interaction (Drs. M, Rowley, G. Fenalti, I.R. Mackay, P.J. Banga).
• Identification of disease-specific autoantibodies and their epitopes in different forms of autoimmune diabetes to aid in diagnosis and classification (Drs. A. Balasubramanyam, I. Hirsch, S. Kahn, T. Maruyama, O. Rolandsson, J. Palmer).
• Identification of disease-specific autoantibodies and their epitopes in Stiff Person Syndrome to aid in better diagnosis.
• Analysis of genetic and environmental effects in autoimmune diabetes (M. Metzker, Z. Laron).
• Identification of autoantibodies and their epitopes during progression to type 1 diabetes (A. Lernmark, M. Schlosser, M. Pietropaolo, J. Ludvigsson).

Anti-idiotypic antibodies
Recently we identified the presence of masked GAD65Ab in the majority of healthy individuals. These autoantibodies are not detected in the regular radioligand binding assay, because they are masked by anti-idiotypic antibodies. Removal of the anti-idiotypic antibodies allows their detection. 
Currently we investigate the role of anti-idiotypic antibodies in the disease pathogenesis both in humans and in animal models for type 1 diabetes. 
The studies encompass the following projects:
• Monoclonal GAD65Ab and their anti-idiotypic antibodies in type 1 diabetes of the NOD mouse (Drs R. LeBoeuf, I. Sweet, J. Taborsky).
• GAD65Ab-specific anti-idiotypic antibodies in the progression to type 1 diabetes.

Role of GAD65Ab in disease pathogenesis
The  central hypothesis is that autoantibody modulation of T cell mediated  autoimmunity plays a key role in the pathogenesis of type 1 diabetes. It is well established  that antibodies can modulate T cell responses either by enhanced  antigen uptake (receptor-mediated endocytosis) or alteration of  antigen processing, or both.  Antibodies can both suppress or boost the presentation of certain peptides, hence the analysis of  heterogeneous GAD65Abs, as present in patients’ sera, will be  difficult.  We use monoclonal GAD65-specific antibodies to test how they deviate the T cell response  already shown to be enhanced by GAD65Ab-positive sera (J. Heinecke).
 

Representative Publications:

Oak S, Gilliam LK, Landin-Olsson M, Törn C, Kockum I, Pennington CR, Rowley MJ, Christie MR, Banga JP, Hampe CS The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes Proc Natl Acad Sci USA 105:5471-6 2008.
 
Hall T R, Bogdani M, LeBoeuf R, Kirk, E, Maziarz M, Banga J P, Oak, S, Pennington C, Hampe CS  Modulation of diabetes in NOD mice by GAD65-specific monoclonal antibodies is epitope specific and accompanied by anti-idiotypic antibodies Immunology;123:547-54 2008.
 
Bekris, LM, Jensen, RA, Lagerquist, E, Hall, TR, Agardh CD, Cilio CM, Lethagen AL, Lernmark, A, Robertson RA, Hampe CS GAD65 autoantibody epitopes in adult patients with latent autoimmune diabetes following GAD65 vaccination Diabet Med 24:521-6 2007.
 
Fenalti G,  Law RHP, Buckle AM, Langendorf C, Tuck K, Rosado CJ,  Faux NG, Mahmood K, Hampe CS, Banga JP, Wilce M, Schmidberger J, Rossjohn J, El-Kabbani O, Pike RN, Smith AI,  Mackay IR,  Rowley MJ,  Whisstock JC   GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop Nat Struct Mol Biol 14:280-6 2007.
 
Maruyama T, Oak S, Hall TR, Banga JP, Ortqvist E, Ettinger RA, Endl  J, Hampe CS  Autoantibody epitopes to the smaller isoform of glutamate decarboxylase do not differ in Swedish and Japanese type 1 diabetes patients and may be associated with high risk HLA class II alleles Clin Exp Immunol  150:416-21 2007.
 
View Expanded Publication List

Current Collaborations:

Within the Diabetes and Obesity Center of Excellence and its Affiliated Members
Irl Hirsch, MD
Jay Taborsky, PhD
Ian Sweet, PhD
Jay Heinecke, MD
Renee LeBoeuf, PhD
Steven Kahn, MB, ChB
Jerry Palmer, MD
Jerry Nepom, MD, PhD
 
Outside the Diabetes and Obesity Center of Excellence
Ake Lernmark, Sweden
Olav Rolandsson, Sweden
Johnny Ludvigsson,  Sweden
Ashok Balasubramanyam, Houston
Taro Maruyama, Japan
Paul Banga, UK
Merrill Rowley, Australia
Massimo Pietropaolo, Michigan

Lab Members:

Shilpa Oak, PhD
Jared Radtke, Lab Manager