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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

该职业发展奖将使候选人能够扩展其旨在了解人类系统性红斑狼疮（SLE）发病机制的研究计划，建立一个以患者为中心的狼疮研究机构计划，并促进感兴趣的临床研究人员的发展在狼疮的研究中。该候选基因已证明补体受体 2 (CR2/CD21) 是 NZM2410 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，以便为已确定的疾病开发更有效的疗法，确定疾病发生前的干预策略，并表征疾病活动的生物标志物协助患者管理。她为两项以患者为导向的研究提供了资金。其中一个项目旨在鉴定 CR2 基因中与人类狼疮相关的功能性单核苷酸多态性 (SNP) 和 SNP 单倍型，并表征这些基因变异影响狼疮易感性的机制。第二个项目探讨 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 相关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（包括初级教师、研究员、住院医生以及医学和 MSTP 学生）提供了以患者为导向的研究的卓越体验。此外，候选人还将建立一个以患者为导向的狼疮机构研究项目，包括转化、结果和流行病学研究以及临床试验，以促进狼疮的临床研究，并为学员提供更多选择。在短期内，该职业发展奖将使候选人能够开发该研究项目，提高其以患者为导向的研究技能，并指导对临床研究职业感兴趣的学员。从长远来看，它将增进我们对狼疮发病机制的了解，导致该疾病的新疗法和预防措施的确定，并增加以患者为导向的研究中训练有素的研究人员的数量。