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Functional analysis of SIRPG, a T cell-specific autoimmune gene

T细胞特异性自身免疫基因SIRPG的功能分析

基本信息

批准号：
10557874
负责人：
I-CHENG HO
金额：
$ 22.38万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10557874
关键词：
Ablation Address Amino Acids Antibodies Autoimmune Autoimmune Diseases Biological Assay CD47 gene Cell surface Cells Clustered Regularly Interspaced Short Palindromic Repeats Coculture Techniques Consensus Data Family Flow Cytometry Gene Expression Profile Genes Genetic Engineering Genetic Transcription Genetic Variation Genetic study Genomic DNA Genotype Goals Health Homologous Gene Human Immunoglobulins In Vitro Individual Insulin-Dependent Diabetes Mellitus Intervention Investigation Lupus Mediating Membrane Molecular Conformation Mus Natural Killer Cells Nucleotides Observational Study Outcome Pathogenesis Pathogenicity Phenotype Physiological Role SHPS-1 protein Signal Transduction Single Nucleotide Polymorphism System T-Lymphocyte Technology Untranslated RNA Variant autoimmune pathogenesis base editing cytokine genome wide association study high risk immune function improved member multiple omics multiple sclerosis patient novel novel therapeutic intervention receptor transcriptome sequencing

项目摘要

Project Summary Recent genetic studies have identified numerous genetic variations that are associated with higher risk of autoimmune diseases. For example, several genetic variations at the SIRPG gene are associated with higher risk of type 1 diabetes. SIRPG is expressed almost exclusively in T lymphocytes. However, its physiological function is still unknown due to the lack of a mouse homologue. Nor do we understand how its genetic variations contribute to the pathogenesis of type 1 diabetes. These important questions will be addressed in this project with cutting edge genetic engineering technology to ablate SIRPG or reproduce its genetic variations in human T cells. Data generated from this project will advance our understanding of not only the function of SIRPG but also the pathogenesis of type 1 diabetes, and eventually lead to novel therapeutic approaches of autoimmune diseases.

项目摘要最近的遗传学研究已经确定了许多与高风险相关的遗传变异，自身免疫性疾病例如，SIRPG基因的几种遗传变异与较高的 1型糖尿病的风险SIRPG几乎仅在T淋巴细胞中表达。然而，其生理由于缺乏小鼠同源物，其功能仍然未知。我们也不知道它的基因变异有助于1型糖尿病的发病机制。这些重要问题将在该项目采用先进的基因工程技术来消除SIRPG或复制其基因，人类T细胞的变异。从这个项目产生的数据将促进我们的理解，不仅 SIRPG的功能，而且1型糖尿病的发病机制，并最终导致新的治疗自身免疫性疾病的方法。