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Lisa Hammerle

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Research paper thumbnail of Ketosis-Prone Diabetes: Dissection of a Heterogeneous Syndrome Using an Immunogenetic and β-Cell Functional Classification, Prospective Analysis, and Clinical Outcomes

The Journal of Clinical Endocrinology & Metabolism, 2003

Ketosis-prone diabetes is heterogeneous. Its causes could include novel β-cell functional defects... more Ketosis-prone diabetes is heterogeneous. Its causes could include novel β-cell functional defects. To characterize such defects, 103 patients with diabetic ketoacidosis were evaluated for β-cell autoimmunity and human leukocyte antigen (HLA) class II alleles, with longitudinal measurements of β-cell function and biochemical and clinical parameters. They were classified into four Aβ groups, based on the presence of glutamic acid decarboxylase (GAD)65, GAD67, or IA-2 autoantibodies (A+ or A−) and β-cell functional reserve (β+ or β−). The group distribution was: 18 A+β−, 23 A−β−, 11 A+β+, and 51 A−β+. Collectively, the two β− groups differed from the two β+ groups in earlier onset and longer duration of diabetes, lower body mass index, less glycemic improvement, and persistent insulin requirement. HLA class II genotyping showed that the A−β− group differed from the A+β− group in having lower frequencies of two alleles strongly associated with autoimmune type 1 diabetes susceptibility: ...

Research paper thumbnail of Rat Islets Express Two Forms of the Microvesicular GABA Transporter VIAAT: Levels of Expression of VIAAT Parallel Islet Cell GAD67 Content

Research paper thumbnail of the Protein and Peptide Levels through Quantitative Proteomics at Both Ubiquitin Ligase Substrate Identification Genomics and Proteomics

Research paper thumbnail of Stable GAD65 Autoantibody Epitope Patterns in Type 1 Diabetes Children Five Years after Onset

Journal of Autoimmunity, Feb 28, 2002

Research paper thumbnail of A novel monoclonal antibody specific for the N-terminal end of GAD65

Journal of Neuroimmunology, 2001

Research paper thumbnail of Recognition of Glutamic Acid Decarboxylase (GAD) by Autoantibodies from Different GAD Antibody-Positive Phenotypes 1

The Journal of Clinical Endocrinology & Metabolism, 2000

Autoantibodies against the smaller isoform of glutamic acid decarboxylase (GAD) are markers for T... more Autoantibodies against the smaller isoform of glutamic acid decarboxylase (GAD) are markers for Type 1 diabetes. GAD65 autoantibody (GAD65Ab)-positive individuals in the general population are, however, mostly at low risk of developing Type 1 diabetes, suggesting that GAD65Ab phenotypes may be associated with different underlying pathogenic processes. The aim of this study was to test the hypothesis that Type 1 diabetes patients (n ϭ 243; group I), GAD65Ab-positive healthy individuals (n ϭ 28; group II), and healthy first-degree relatives of Type 1 diabetes patients (n ϭ 41; group III) have antibody phenotypes that recognize different GAD65 epitopes. Sera from groups I-III were tested for their binding to GAD65 and GAD67, as well as six different GAD65/67 fusion proteins. Regardless of group, sera reactive to both GAD65 and GAD67 showed broader epitope reactivity than GAD65-specific sera. Furthermore, Type 1 diabetes patients showed a more restricted epitope binding than healthy individuals and first-degree relatives, demonstrating significantly less binding to the N-terminal part of GAD65 and to GAD67. Our analysis demonstrates that the N-terminal part is essential for full antibody binding to GAD65, in particular, to the middle epitope. It is suggested that Type 1 diabetes is associated with restricted GAD65Ab epitope specificity. (J Clin Endocrinol Metab 85: [4671][4672][4673][4674][4675][4676][4677][4678][4679] 2000)

Research paper thumbnail of Ubiquitin Ligase Substrate Identification through Quantitative Proteomics at Both the Protein and Peptide Levels

Journal of Biological Chemistry, 2011

Background: Identification of ubiquitin ligase substrates remains an unmet challenge. Results: Tw... more Background: Identification of ubiquitin ligase substrates remains an unmet challenge. Results: Two proteomic strategies were used to identify novel substrates of the E3 ligase HRD1. Conclusion: These methods identified populations of substrates enriched for potential targets of endoplasmic reticulumassociated degradation. Significance: This approach should be broadly useful for E3 ligase substrate identification, and the identified substrates provide insight into the role of HRD1 in disease.

Research paper thumbnail of Stable GAD65 Autoantibody Epitope Patterns in Type 1 Diabetes Children Five Years after Onset

Journal of Autoimmunity, 2002

Research paper thumbnail of Site-directed mutagenesis of K396R of the 65 kDa glutamic acid decarboxylase active site obliterates enzyme activity but not antibody binding

FEBS Letters, 2001

The role of K396 in the enzymatic catalysis and the antigenicity of the 65 kDa isoform of glutama... more The role of K396 in the enzymatic catalysis and the antigenicity of the 65 kDa isoform of glutamate decarboxylase (GAD65) was analyzed using the K396R GAD65 mutant. GAD65 is a major autoantigen in Type 1 diabetes and autoantibodies directed to GAD65 are widely used markers for this disease. We found that (1) recombinant human GAD65 is fully enzymatically active; (2) the K396R mutation abolished GAD65 activity; and (3) the K396R mutant retained full antigenicity to GAD65 autoantibodies in serum from Type 1 diabetes patients, but not to polyclonal antibodies raised to the catalytic domain. ß

Research paper thumbnail of Expression of the Vesicular Inhibitory Amino Acid Transporter in Pancreatic Islet Cells : Distribution of the Transporter Within Rat Islets

Diabetes, 2002

Analysis, cloning, and expression of human VIAAT cDNA. A candidate human VIAAT gene was identifie... more Analysis, cloning, and expression of human VIAAT cDNA. A candidate human VIAAT gene was identified by using BLAST (

Research paper thumbnail of Preservation of Enzyme Activity and Antigenicity after Mutagenesis of the Membrane Anchoring Domain of GAD65

Research paper thumbnail of Ketosis-prone diabetes: Dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes

Journal of Clinical Endocrinology Amp Metabolism, Dec 1, 2003

Research paper thumbnail of Ketosis-Prone Diabetes: Dissection of a Heterogeneous Syndrome Using an Immunogenetic and β-Cell Functional Classification, Prospective Analysis, and Clinical Outcomes

The Journal of Clinical Endocrinology & Metabolism, 2003

Ketosis-prone diabetes is heterogeneous. Its causes could include novel β-cell functional defects... more Ketosis-prone diabetes is heterogeneous. Its causes could include novel β-cell functional defects. To characterize such defects, 103 patients with diabetic ketoacidosis were evaluated for β-cell autoimmunity and human leukocyte antigen (HLA) class II alleles, with longitudinal measurements of β-cell function and biochemical and clinical parameters. They were classified into four Aβ groups, based on the presence of glutamic acid decarboxylase (GAD)65, GAD67, or IA-2 autoantibodies (A+ or A−) and β-cell functional reserve (β+ or β−). The group distribution was: 18 A+β−, 23 A−β−, 11 A+β+, and 51 A−β+. Collectively, the two β− groups differed from the two β+ groups in earlier onset and longer duration of diabetes, lower body mass index, less glycemic improvement, and persistent insulin requirement. HLA class II genotyping showed that the A−β− group differed from the A+β− group in having lower frequencies of two alleles strongly associated with autoimmune type 1 diabetes susceptibility: ...

Research paper thumbnail of Rat Islets Express Two Forms of the Microvesicular GABA Transporter VIAAT: Levels of Expression of VIAAT Parallel Islet Cell GAD67 Content

Research paper thumbnail of the Protein and Peptide Levels through Quantitative Proteomics at Both Ubiquitin Ligase Substrate Identification Genomics and Proteomics

Research paper thumbnail of Stable GAD65 Autoantibody Epitope Patterns in Type 1 Diabetes Children Five Years after Onset

Journal of Autoimmunity, Feb 28, 2002

Research paper thumbnail of A novel monoclonal antibody specific for the N-terminal end of GAD65

Journal of Neuroimmunology, 2001

Research paper thumbnail of Recognition of Glutamic Acid Decarboxylase (GAD) by Autoantibodies from Different GAD Antibody-Positive Phenotypes 1

The Journal of Clinical Endocrinology & Metabolism, 2000

Autoantibodies against the smaller isoform of glutamic acid decarboxylase (GAD) are markers for T... more Autoantibodies against the smaller isoform of glutamic acid decarboxylase (GAD) are markers for Type 1 diabetes. GAD65 autoantibody (GAD65Ab)-positive individuals in the general population are, however, mostly at low risk of developing Type 1 diabetes, suggesting that GAD65Ab phenotypes may be associated with different underlying pathogenic processes. The aim of this study was to test the hypothesis that Type 1 diabetes patients (n ϭ 243; group I), GAD65Ab-positive healthy individuals (n ϭ 28; group II), and healthy first-degree relatives of Type 1 diabetes patients (n ϭ 41; group III) have antibody phenotypes that recognize different GAD65 epitopes. Sera from groups I-III were tested for their binding to GAD65 and GAD67, as well as six different GAD65/67 fusion proteins. Regardless of group, sera reactive to both GAD65 and GAD67 showed broader epitope reactivity than GAD65-specific sera. Furthermore, Type 1 diabetes patients showed a more restricted epitope binding than healthy individuals and first-degree relatives, demonstrating significantly less binding to the N-terminal part of GAD65 and to GAD67. Our analysis demonstrates that the N-terminal part is essential for full antibody binding to GAD65, in particular, to the middle epitope. It is suggested that Type 1 diabetes is associated with restricted GAD65Ab epitope specificity. (J Clin Endocrinol Metab 85: [4671][4672][4673][4674][4675][4676][4677][4678][4679] 2000)

Research paper thumbnail of Ubiquitin Ligase Substrate Identification through Quantitative Proteomics at Both the Protein and Peptide Levels

Journal of Biological Chemistry, 2011

Background: Identification of ubiquitin ligase substrates remains an unmet challenge. Results: Tw... more Background: Identification of ubiquitin ligase substrates remains an unmet challenge. Results: Two proteomic strategies were used to identify novel substrates of the E3 ligase HRD1. Conclusion: These methods identified populations of substrates enriched for potential targets of endoplasmic reticulumassociated degradation. Significance: This approach should be broadly useful for E3 ligase substrate identification, and the identified substrates provide insight into the role of HRD1 in disease.

Research paper thumbnail of Stable GAD65 Autoantibody Epitope Patterns in Type 1 Diabetes Children Five Years after Onset

Journal of Autoimmunity, 2002

Research paper thumbnail of Site-directed mutagenesis of K396R of the 65 kDa glutamic acid decarboxylase active site obliterates enzyme activity but not antibody binding

FEBS Letters, 2001

The role of K396 in the enzymatic catalysis and the antigenicity of the 65 kDa isoform of glutama... more The role of K396 in the enzymatic catalysis and the antigenicity of the 65 kDa isoform of glutamate decarboxylase (GAD65) was analyzed using the K396R GAD65 mutant. GAD65 is a major autoantigen in Type 1 diabetes and autoantibodies directed to GAD65 are widely used markers for this disease. We found that (1) recombinant human GAD65 is fully enzymatically active; (2) the K396R mutation abolished GAD65 activity; and (3) the K396R mutant retained full antigenicity to GAD65 autoantibodies in serum from Type 1 diabetes patients, but not to polyclonal antibodies raised to the catalytic domain. ß

Research paper thumbnail of Expression of the Vesicular Inhibitory Amino Acid Transporter in Pancreatic Islet Cells : Distribution of the Transporter Within Rat Islets

Diabetes, 2002

Analysis, cloning, and expression of human VIAAT cDNA. A candidate human VIAAT gene was identifie... more Analysis, cloning, and expression of human VIAAT cDNA. A candidate human VIAAT gene was identified by using BLAST (

Research paper thumbnail of Preservation of Enzyme Activity and Antigenicity after Mutagenesis of the Membrane Anchoring Domain of GAD65

Research paper thumbnail of Ketosis-prone diabetes: Dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes

Journal of Clinical Endocrinology Amp Metabolism, Dec 1, 2003

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