Molecular Genetics and Immunoregulatory mechanisms of PFAPA syndrome

PFAPA综合征的分子遗传学和免疫调节机制

• 批准号: 8635233
• 负责人: Lori Broderick
• 金额: $ 13.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635233
• 关键词: Adenitis; Advisory Committees; Affect; Antigens; Aphthous Stomatitis; B-Cell Development; B-Lymphocytes; Biological Response Modifiers; Blood; Buffaloes; California; Candidate Disease Gene; Cell Proliferation; Cell physiology; Cells; Cervical; Child; Childhood; Clinical; Coculture Techniques; DNA; DNA Methylation; Data; Dendritic Cells; Development; Development Plans; Disease; Doctor of Philosophy; Educational workshop; Environment; Epigenetic Process; Etiology; Evaluation; Event; Familial Mediterranean Fever; Family; Fellowship; Fever; Functional disorder; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Gene Mutation; Generations; Genes; Genetic; Genomics; Genotype; Goals; Histone Acetylation; Histone Deacetylase; Histone Deacetylase Inhibitor; Hypersensitivity; Immune; Immune system; Immunology; In Vitro; Inflammatory; Inherited; Interleukin-1; Investigation; Journals; Laboratories; Leukocytosis; Maintenance; Medical; Medicine; Memory B-Lymphocyte; Mentors; Methylation; Methyltransferase; Microarray Analysis; Modification; Molecular Genetics; Molecular Profiling; Mutation; Natural Immunity; Obstructive Sleep Apnea; Oropharyngeal; Parents; Pathogenesis; Pathway interactions; Patients; Pediatrics; Pharyngitis; Physicians; Population; Principal Investigator; Production; Program Development; Quality of life; Recording of previous events; Recurrence; Regulation; Reporting; Research; Research Personnel; Residencies; Resolution; Role; Saliva; Sampling; Scientist; Source; Stomatitis; Symptoms; Syndrome; T-Lymphocyte; Time; Tissues; Tonsil; Tonsillectomy; Training; Training Programs; Training Technics; Universities; Variant; base; career; career development; chromatin immunoprecipitation; clinical phenotype; cytokine; exome sequencing; histone acetyltransferase; histone modification; member; offspring; pediatric department; prednisolone; primary outcome; professor; public health relevance; response; segregation; skills; therapeutic target; trait; tumor immunology

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of a career as a physician- scientist. The principal investigator has completed a PhD thesis at the University at Buffalo in tumor immunology, and Pediatric residency and Allergy/Immunology fellowship training at the University of California at San Diego. She will expand upon her scientific skills through a focused career development plan and training in molecular genetics as applied to immune dysregulation in pediatrics. Dr. Hal Hoffman is a Professor of Pediatrics and Medicine at UC San Diego and will mentor the principal investigator's scientific and career development. Dr. Hoffman is a globally recognized leader in autoinflammatory disorders. An advisory committee of scientists, including Dr. Kelly Frazer who has expertise in the role of genomics in pediatric disease, will provide additional career and project guidance. In addition, intensive workshops, seminars, journal clubs, and specific laboratory technique training will accompany ample protected research time. The academic environment in the Department of Pediatrics at UCSD supports the development of independent, translational investigators. Scientific investigations will focus on the genetic and immunoregulatory mechanisms of Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome, a systemic inflammatory disorder of childhood characterized by recurrent episodes of fever, oropharyngeal signs, cervical adenitis and leukocytosis in otherwise healthy children. The underlying etiology of PFAPA is unknown and therapies are limited; both are issues which negatively impact the quality of life for patients and their families. The specific goals of this project are: 1) to identify the genetic basis of PFAPA syndrome using DNA collected from families with multiple members that have a history of PFAPA, 2) to investigate the patterns of gene expression in tissue from PFAPA patients undergoing tonsillectomy with a focus on IL-1-related pathways and B cells, and 3) to evaluate the role of DNA methylation and histone acetylation events in tonsils as a regulatory mechanism in the pathogenesis of PFAPA.

描述（由申请人提供）：本提案描述了一个为期5年的培训计划，作为一个医生，科学家的职业发展。主要研究者在布法罗大学完成了肿瘤免疫学博士论文，并在圣地亚哥的加州大学完成了儿科住院医师和过敏/免疫学奖学金培训。她将通过有重点的职业发展计划和分子遗传学培训来扩展她的科学技能，以应用于儿科免疫失调。Hal霍夫曼博士是加州大学圣地亚哥分校的儿科和医学教授，他将指导主要研究者的科学和职业发展。霍夫曼博士是全球公认的自身炎症性疾病的领导者。一个科学家咨询委员会，包括凯利弗雷泽博士谁在儿科疾病的基因组学的作用的专业知识，将提供额外的职业和项目指导。此外，密集的讲习班，研讨会，期刊俱乐部和具体的实验室技术培训将伴随着充足的保护研究时间。UCSD儿科系的学术环境支持独立的翻译研究人员的发展。 科学研究将集中于周期性发热、口疮性口炎、咽炎和腺样体炎（PFAPA）综合征的遗传和免疫调节机制，这是一种儿童全身性炎症性疾病，其特征是在其他健康儿童中反复发作发热、口咽体征、颈淋巴结炎和白细胞增多。PFAPA的潜在病因尚不清楚，治疗方法有限;这两个问题都会对患者及其家属的生活质量产生负面影响。该项目的具体目标是：1）使用从具有PFAPA病史的多个成员的家族收集的DNA鉴定PFAPA综合征的遗传基础，2）研究来自经历扁桃体切除术的PFAPA患者的组织中的基因表达模式，重点是IL-1相关途径和B细胞，评估扁桃体中DNA甲基化和组蛋白乙酰化事件在PFAPA发病机制中的调节作用。