IL29 and IL28B Variants Associated with Periodontal Disease Pathogenesis

IL29 和 IL28B 变异体与牙周病发病机制相关

• 批准号: 9303344
• 负责人: Thiago Morelli
• 金额: $ 6.35万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-02-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303344
• 关键词: Active Learning; Adaptive Immune System; Advisory Committees; Affect; Alleles; Applications Grants; Area; Award; Basic Science; Biological; Biological Markers; Caucasians; Cells; Clinical; Clinical Data; Clinical Research; Clinical Sciences; Committee Members; Complex; Data; Dendritic Cells; Dental Epidemiology; Dental Hygiene; Dentistry; Development; Development Plans; Disease; Disease susceptibility; Education; Environmental Risk Factor; Epidemiologist; Ethics; Etiology; Exhibits; Foundations; Funding; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genomics; Gills; Gingival Crevicular Fluid; Gingivitis; Goals; Grant; Group Meetings; Hereditary Disease; Human; Immunologist; In Vitro; Individual; Infection; Inflammatory; Inflammatory Response; Innate Immune Response; Investigation; K-Series Research Career Programs; Lead; Ligands; Link; Measures; Mediating; Mediator of activation protein; Medicine; Mendelian disorder; Mentored Patient-Oriented Research Career Development Award; Mentors; Microbe; Microbial Biofilms; Minor; Modeling; Molecular; Mouth Diseases; National Institute of Dental and Craniofacial Research; Oral health; Pathogenesis; Pathogenicity; Patients; Pattern; Periodontal Diseases; Periodontitis; Population; Population Study; Predisposition; Public Health; Publishing; Regulation; Reporting; Research; Research Design; Research Personnel; Research Project Grants; Research Proposals; Resources; Risk; Role; School Dentistry; Schools; Scientist; Single Nucleotide Polymorphism; Stents; Structure; Systemic disease; Time; Toll-like receptors; Training; Translational Research; Translations; United States National Institutes of Health; Variant; Viral; career; career development; clinical application; clinically relevant; cohort; collaborative environment; cytokine; experience; genetic epidemiology; genetic variant; genome wide association study; genome-wide; high standard; human subject; insight; member; microbial community; microbial host; novel; novel diagnostics; novel therapeutic intervention; oral commensal; osteoimmunology; pathogen; patient oriented research; professor; public health relevance; response; risk variant; skills; tool; transmission process; treatment strategy

 DESCRIPTION (provided by applicant): This grant application titled, "IL29 and IL28B variants associated with periodontal disease pathogenesis", is a Mentored Patient-Oriented Research Career Development Award (K23) proposal under the guidance of Steven Offenbacher (UNC, School of Dentistry). The training and research plan represent outgrowths of my clinical training and emerging translational research; the research project centers on the most pressing current clinical dilemma faced in Periodontal Pathogenesis: genetic predisposition. Results obtained from a genome- wide association study (GWAS) identified genes important for several aspects of periodontal disease, particularly IL29 and IL28B, which are involved with modulating the innate and adaptive immune system in response to bacterial and viral challenge. The overall goals of this career development award are to provide the candidate with the necessary didactic and experiential learning to facilitate his transition to an independent investigator and to determine the clinical relevance of minor allelic variants of IL28B and IL29 with the expression of chronic periodontitis. Aim 1 will be used to determine the impact of SNP variants on periodontal disease expression and local inflammatory response during stent-induced biofilm overgrowth. This model, which is a contemporary version of the classic experimental gingivitis model, will be used to evaluate the influence of IL28B and IL29 SNP variants on the clinical response to biofilm overgrowth, as compared to the dominant allelic variants. Aim 2 will evaluate in vitro the impact of SNP variants on cell-mediated, innate inflammatory response. This reverse translational aim will evaluate the impact of the minor allelic SNP variants of IL28B and IL29 on cytokine responses of dendritic cells. To accomplish the goals of this proposal, the candidate has access to a unique collaborative environment including Periodontists, Epidemiologist, Microbiologists, Immunologists, and a Biostatistician from the resources of the UNC Schools of Dentistry, Medicine, and Gillings Public Health. There are programmatic links between these schools and individuals that will allow on-going interactions with a very diverse group of clinicians and researchers who focus on the oral health. The primary mentor, Steven Offenbacher is a Professor of Periodontology at the School of Dentistry. He has an established record of NIH funding through NIDCR with expertise in most areas of periodontal research (both clinical and basic science) including education, systemic diseases, implantology, osteoimmunology, andgenetics. The Research Advisory Committee members, Ricardo Teles, Kari North, Jennifer Webster-Cyriaque, and John Preisser, each bring distinct strengths to the Committee. Dr. Teles has expertise in clinical research, periodontal disease pathogenesis, and microbial and host-derived biomarkers. Dr. North expertise includes Genetic Epidemiology and Statistical Genetics. Dr. Webster-Cyriaque is an immunologist with experience with molecular pathogenesis in oral disease and an established record of NIH funding. Dr. Preisser's main collaborative research is in dentistry, including oral epidemiology and biological mechanisms of periodontal disease. He has collaborated with the Offenbacher group for several years. The members of the Research Advisory Committee are accomplished researchers in their respective fields and will provide insights into the development and execution of the research strategy plan, and most importantly provide mentoring through my developmental career plan. The goals during the this five-year award period are to become an independent scientist, with deeper understanding of research design, the ethical treatment of human subjects, and the role of genomics on periodontal disease pathogenesis. The five-year framework of the grant will provide the tools and skills to become an independent researcher. The candidate will use the training and research accomplished in this award to prepare for a competitive R01 grant application.

 描述（由应用程序提供）：该赠款申请为“与牙周疾病发病机理相关的IL29和IL28B变体”，是一项受过指导的面向患者的研究职业发展奖（K23）的建议，在Steven Offenbacher（UNC，牙科学院）的指导下。培训和研究计划代表了我的临床培训和新兴转化研究的生长；研究项目集中在牙周发病机理中面临的最紧迫的当前临床困境：遗传倾向。从全基因组关联研究（GWAS）获得的结果确定了对牙周疾病的多个方面，尤其是IL29和IL28B重要的基因，这些基因涉及对细菌和病毒挑战的调节对天生和适应性免疫系统的调节。 该职业发展奖的总体目标是为候选人提供必要的教学和经验丰富的学习，以促进他向独立研究者的过渡，并确定IL28B和IL29的次要等位基因变体的临床相关性，并表达慢性牙周炎。 AIM 1将用于确定SNP变体对支架诱导的生物膜过度生长期间牙周疾病表达和局部炎症反应的影响。 AIM 2将在体外评估SNP变体对细胞介导的先天炎症反应的影响。这种反向翻译目标将评估IL28B和IL29的次要等位基因SNP变体对树突状细胞细胞因子反应的影响。 为了实现该提案的目标，候选人可以访问独特的协作环境，包括牙周病学家，流行病学家，微生物学家，免疫学家，以及来自UNC牙科，医学和吉林斯公共卫生学院资源的生物统计学家。这些学校与个人之间存在程序化联系，这些联系将允许与专注于口腔健康的非常多样化的临床医生和研究人员进行持续的互动。 主要导师史蒂芬·奥芬巴赫（Steven Offenbacher）是牙科学院牙周病学教授。他通过NIDCR拥有既定的NIH资金记录，并在大多数牙周研究领域（临床和基础科学）领域具有专业知识，包括教育，全身疾病，不抗抑制，骨气免疫学和遗传学。研究咨询委员会成员Ricardo Teles，Kari North，Jennifer Webster-Cyriaque和John Preisser为委员会带来了不同的优势。 Teles博士在临床研究，牙周疾病发病机理以及微生物和宿主衍生的生物标志物方面具有专业知识。 North博士的专业知识包括遗传流行病学和统计遗传学。 Webster-Cyriaque博士是一名免疫学家，具有口腔疾病中分子发病机理的经验，并具有NIH资金的既定记录。 Preisser博士的主要合作研究是牙科，包括口腔流行病学和牙周疾病的生物学机制。他已经与Offenbacher集团合作了几年。研究咨询委员会的成员是各自领域的成就研究人员，并将提供有关研究战略计划的制定和执行的见解，最重要的是通过我的发展职业计划提供心理。 五年奖励期间的目标是成为一名独立科学家，对研究设计，人类受试者的道德处理以及基因组学对牙周疾病发病机理的作用有了更深入的了解。赠款的五年框架​​将为成为独立研究人员提供工具和技能。候选人将使用该奖项中完成的培训和研究来为有竞争力的R01赠款申请做准备。

项目成果

Gingival crevicular fluid as a source of biomarkers for periodontitis.

• DOI: 10.1111/prd.12107
• 发表时间: 2016-02
• 期刊: Periodontology 2000
• 影响因子: 18.6
• 作者: Barros SP;Williams R;Offenbacher S;Morelli T
• 通讯作者: Morelli T