Analysis of Lupus Susceptibility Genes for Treatment and Prevention of Disease

狼疮易感基因分析用于治疗和预防疾病

• 批准号: 8291280
• 负责人: SUSAN A. BOACKLE
• 金额: $ 14.78万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-24 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8291280
• 关键词: 1q32; 5' Untranslated Regions; Address; Affect; Alleles; Alternative Splicing; Animal Model; Antigen Presentation; Antigen-Antibody Complex; Antigens; Applications Grants; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Bacterial Artificial Chromosomes; Binding; Biological Markers; CD46 Antigen; Candidate Disease Gene; Caucasians; Caucasoid Race; Cell physiology; Childhood; Chinese People; Chromosomes; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Collaborations; Colorado; Complement; Complement 3d Receptors; Complement Activation; Complement Receptor; Data; Department of Defense; Development; Disease; Epidemiology; Ethnic group; Exons; Faculty; Family member; First Degree Relative; Follicular Dendritic Cells; Fostering; Foundations; Functional disorder; Funding; Funding Agency; Gene Cluster; Genes; Genetic; Genetic Transcription; Genetic Variation; Goals; Grant; Haplotypes; Human; Immune response; In Vitro; Individual; Intervention; K-Series Research Career Programs; Lead; Ligand Binding; Link; Linkage Disequilibrium; Lupus; Mature B-Lymphocyte; Measures; Medical; Medical Research; Membrane Glycoproteins; Mentors; Methods; Minor; Modeling; Mus; Oklahoma; Outcome; Parents; Pathogenesis; Patients; Phenotype; Play; Population; Positioning Attribute; Predisposition; Preventive; Process; Protein Isoforms; Proteins; RNA Splicing; Research; Research Personnel; Research Support; Risk; Role; Secure; Self Tolerance; Single Nucleotide Polymorphism; Staging; Students; Susceptibility Gene; Systemic Lupus Erythematosus; Therapeutic; To autoantigen; Training; Transgenic Mice; United States National Institutes of Health; Universities; autoreactive B cell; base; career; cofactor; cohort; cost; design; disorder prevention; effective therapy; experience; genetic variant; human disease; human subject; in vivo; interest; investigator training; mouse development; mouse model; patient oriented research; pre-clinical; prevent; programs; sample collection; skills; transcription factor; vector

This career development award will allow the candidate to expand her research program directed towards understanding the pathogenesis of human systemic lupus erythematosus (SLE), to build an institutional program in patient-oriented research focused on lupus, and to foster the development of clinical researchers interested in the study of lupus. The candidate has demonstrated that complement receptor 2 (CR2/CD21) is a strong candidate gene for lupus susceptibility in the NZM2410 mouse model of lupus as well as in human disease. Her long-term goals are to dissect the functional relevance of lupus susceptibility genes in the pathogenesis of lupus in order to develop more effective therapies for established disease, to identify strategies for intervention prior to the development of disease, and to characterize biomarkers for disease activity to assist in patient management. She has funding for two patient-oriented studies. One project aims to identify functional single-nucleotide polymorphisms (SNPs) and SNP haplotypes in the CR2 gene that are associated with human lupus and characterize the mechanism by which these gene variants influence lupus susceptibility. The second project addresses whether B cell levels of CR2 are a biomarker for lupus disease activity. A third project developed for this grant mechanism will address whether complement-related genes in linkage with CR2 contribute to the association of CR2 SNPs with SLE and whether CR2 risk alleles are associated with the development of preclinical autoimmunity. These projects offer an excellent experience in patient-oriented research to mentees, including junior faculty, fellows, residents, and medical and MSTP students. In addition, the candidate will build an institutional patient-oriented research program in lupus encompassing translational, outcomes, and epidemiological research as well as clinical trials to facilitate clinical research in lupus and offer additional options for trainees. In the short term, this career development award will allow the candidate in develop this research program, enhance her skills in patient-oriented research, and mentor trainees interested in careers in clinical research. In the long term, it will advance our understanding of the pathogenesis of lupus, lead to the identification of new therapies and preventive measures for this disease, and increase the number of well-trained investigators in patient-oriented research.

该职业发展奖将允许候选人扩大她的研究计划，旨在了解人类系统性红斑狼疮（SLE）的发病机制，建立以患者为导向的研究机构计划，重点关注狼疮，并促进对狼疮研究感兴趣的临床研究人员的发展。该候选人已经证明，补体受体2（CR2/CD 21）是NZM 2410狼疮小鼠模型以及人类疾病中狼疮易感性的强候选基因。她的长期目标是剖析狼疮易感基因在狼疮发病机制中的功能相关性，以便为已建立的疾病开发更有效的治疗方法，在疾病发展之前确定干预策略，并表征疾病活动的生物标志物，以协助患者管理。她资助了两项以病人为导向的研究。其中一个项目旨在鉴定与人类狼疮相关的CR2基因中的功能性单核苷酸多态性（SNP）和SNP单倍型，并描述这些基因变异影响狼疮易感性的机制。第二个项目解决了CR2的B细胞水平是否是狼疮疾病活动的生物标志物。为该资助机制开发的第三个项目将解决与CR2连锁的补体相关基因是否有助于CR2 SNP与SLE的关联，以及CR2风险等位基因是否与临床前自身免疫的发展相关。这些项目为学员提供了以患者为导向的研究方面的良好体验，包括初级教师，研究员，居民以及医学和MSTP学生。此外，候选人将建立一个以患者为导向的机构狼疮研究计划，包括翻译，成果和流行病学研究以及临床试验，以促进狼疮的临床研究，并为学员提供额外的选择。在短期内，这个职业发展奖将允许候选人开发这个研究计划，提高她在以患者为导向的研究中的技能，并指导对临床研究职业感兴趣的学员。从长远来看，它将促进我们对狼疮发病机制的理解，导致确定这种疾病的新疗法和预防措施，并增加训练有素的研究人员的数量。