Exploring knowledge gaps in childhood caries through integrated biological and clinical research

项目概要/摘要 龋齿是最常见的慢性传染性儿童疾病，对儿童的 生活质量尽管龋齿是可以预防的，但龋齿的高患病率仍然存在， 改善对这一年轻弱势群体的诊断和治疗干预。来 近年来，龋病研究取得了重大进展。尽管取得了这些进展，但研究差距仍然存在， 限制了回答两个基本问题的能力：1）为什么不是所有具有升高水平的个体 变形链球菌（Streptococcus mutans，Sm）是一种重要的致龋细菌，它能引起龋病吗？2)主持人如何 遗传变异导致龋齿的易感性？前者仍然是一个重大的谜， 口腔微生物学领域。虽然宿主易感性已被认为是一个重要的决定因素， 医学传染病，它仍然是龋齿研究中研究不足的因素。Nini Tran博士，助理 加州大学洛杉矶分校牙科学院教授，是一位儿科牙医科学家，受过全面的培训， 长期致力于研究事业。职业发展计划使Tran博士能够获得 在三个领域的额外专业知识：1）微生物学和微生物组研究，2）生物统计学和 生物信息学; 3）唾液诊断学。Tran博士将得到杰出的多学科指导的支持 我们的团队拥有专业知识，涵盖了她的研究和职业发展的所有要素。大卫黄博士，一个先驱 在唾液诊断领域，是她的主要导师;史文源博士，杰夫米勒博士，雷娜特勒克斯博士，博士。 何雪松博士、弗洛伊德Dewhirst博士和Ann格里芬博士是微生物学和微生物组学方面的领先专家; 大卫Elashoff提供生物统计学支持，而杰夫姆克林博士具有下一代的专业知识 测序和生物信息学分析。通过量身定制的课程、讲习班和 拟议的研究，博士陈将发展关键技能，以实现她成为一个成功的目标， 儿童龋齿诊断和治疗领域的独立临床医生和科学家。本研究 调查了一个不和谐的学龄前儿童群体，他们的龋齿状况与预期的相矛盾， 在他们的Sm水平上与相应的对应物相比。整合创新的研究设计和新颖的 工具，研究计划的目的是1）表征Sm菌株的个性和它的生态关系， 不同的微生物群落，2）探索与儿童龋齿相关的唾液宿主生物标志物，以及3）验证 Sm相关微生物毒力特征和宿主唾液生物标志物， 龋齿评估这项研究将为R 01提案奠定基础，重点是口腔微生物组间的相互作用。 种间相互作用，宿主和口腔微生物间相互作用与儿童龋齿易感性有关， 儿童龋齿诊断和治疗的发展。最后，这个奖项将使陈博士 成为一名顶级的儿科牙医科学家，并使她能够为该领域做出重大贡献。 民国儿童牙科医学

Project Summary/Abstract Dental caries, the most common, chronic, infectious childhood disease, has a substantial impact on children’s quality of life. The high prevalence of dental caries that persists despite its preventability necessitates improvement in diagnostics and therapeutic interventions for this young and vulnerable population. Over the years, significant progress has been made in caries research. Despite these advances, research gaps remain, limiting the ability to answer two fundamental questions: 1) Why do not all individuals with elevated levels of Streptococcus mutans (Sm), an important infectious, cariogenic bacterium, develop caries? 2) How does host genetic variation contribute to the susceptibility to dental caries? The former continues to be a major enigma in the field of oral microbiology. Though host susceptibility has been recognized as an important determinant in medical infectious diseases, it remains an under-studied factor in caries research. Dr. Nini Tran, an Assistant Professor at the UCLA School of Dentistry, is a pediatric dentist-scientist with a well-rounded training and a long-standing commitment to a research career. The career development plan enables Dr. Tran to gain additional expertise in three areas: 1) Microbiology and microbiome research, 2) biostatistics and bioinformatics, 3) saliva diagnostics. Dr. Tran will be supported by an outstanding multidisciplinary mentoring team with expertise to cover all elements of her research and career development. Dr. David Wong, a pioneer in the field of saliva diagnostics, is her primary mentor; Dr. Wenyuan Shi, Dr. Jeff Miller, Dr. Renate Lux, Dr. Xuesong He, Dr. Floyd Dewhirst, and Dr. Ann Griffen are the leading microbiology and microbiome experts; Dr. David Elashoff provides biostatistics support, while Dr. Jeff McLean has expertise in next-generation sequencing and bioinformatics analyses. Through a tailored curriculum of courses, workshops and the proposed research, Dr. Tran will develop crucial skills to achieve her goal of becoming a successful independent clinician-scientist in the field of childhood caries diagnostics and therapeutics. This research investigates a discordant, preschool child population whose caries status contradicts what is expected based on their Sm level in comparison to the accordance counterpart. Integrating innovative study design and novel tools, the research plan aims to 1) characterize Sm strain individuality and its ecological relationship within different microbial communities, 2) explore salivary host biomarkers related to childhood caries, and 3) validate Sm-associated microbial virulence signatures and host salivary biomarkers for precise and comprehensive caries assessment. This research will generate the basis for R01 proposals, focusing on oral microbiome inter- species interaction, and host and oral microbial interaction related to childhood caries susceptibility, and the development of diagnostics and therapeutics for childhood caries. Finally, this award will position Dr. Tran to become a top tier pediatric dentist-scientist, and enable her to make a significant contribution to the field of pediatric dentistry.