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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

基本信息

批准号：
9254587
负责人：
Lori Broderick
金额：
$ 17.65万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
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/9254587
关键词：
Adenitis Advisory Committees Affect Antigens Aphthous Stomatitis B-Lymphocytes Biological Response Modifiers Blood Buffaloes California Candidate Disease Gene Cell Compartmentation Cell Proliferation Cell physiology Cells Cervical Child Childhood Clinical Coculture Techniques DNA DNA Methylation DNA Sequence Alteration 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 Generations Genes Genetic Genomics Genotype Global Change 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 Operative Surgical Procedures Oropharyngeal Parents Pathogenesis Pathway interactions Patients Pediatrics Periodicity Pharyngitis Physicians Population Principal Investigator Production Program Development Quality of life Recording of previous events Recurrence Reporting Research Residencies Resolution Role Saliva Sampling Scientist Source Stomatitis Symptoms Syndrome T-Lymphocyte Time Tissues Tonsil Tonsillectomy Training Training Programs Training Technics Universities Variant autoinflammatory career career development chromatin immunoprecipitation clinical phenotype cytokine exome sequencing genome wide methylation histone acetyltransferase histone modification immunoregulation member offspring pediatric department prednisolone primary outcome professor public health relevance response segregation skills therapeutic target trait translational scientist tumor immunology

项目摘要

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(由申请者提供)：这份建议书描述了一项为期5年的内科科学家职业发展培训计划。这位首席研究员在布法罗大学完成了肿瘤免疫学博士论文，并在加州大学圣地亚哥分校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应用于儿科免疫失调的分子遗传学培训来扩展她的科学技能。哈尔·霍夫曼博士是加州大学圣地亚哥分校的儿科学和医学教授，将指导这位首席研究员的科学和职业发展。霍夫曼博士是全球公认的自体炎症性疾病领域的领导者。一个由科学家组成的顾问委员会将提供额外的职业和项目指导，其中包括在基因组学在儿科疾病中的作用方面拥有专业知识的凯利·弗雷泽博士。此外，密集的研讨会、研讨会、期刊俱乐部和特定的实验室技术培训将伴随着充足的受保护研究时间。加州大学圣迭戈分校儿科的学术环境支持独立的、转译的调查人员的发展。科学研究将集中于周期性发热、口腔炎、咽炎和腺炎综合征(PFAPA)的遗传和免疫调节机制，这是一种儿童系统性炎症性疾病，其特征是在其他健康的儿童中反复发作发烧、口咽症状、颈炎和白细胞增多。PFAPA的潜在病因尚不清楚，治疗方法也有限；这两个问题都对患者及其家人的生活质量产生了负面影响。该项目的具体目标是：1)使用从有PFAPA病史的多成员家庭收集的DNA来确定PFAPA综合征的遗传基础；2)研究接受扁桃体切除术的PFAPA患者组织中基因表达的模式，重点是IL-1相关途径和B细胞；3)评估扁桃体DNA甲基化和组蛋白乙酰化事件在PFAPA发病机制中的作用。