The Importance of Periostin in Periodontal Health and Disease

描述(由申请人提供)：应聘者在口腔和分子生物学方面的背景以及他在牙周病学方面的培训使他拥有探索创新方法来理解和解决临床相关健康问题的工具。本申请中提出的培训和研究旨在提高他的调查技能，将重要的实验室发现转化为临床领域，最终目标是发展成为一名独立的临床和翻译科学家。拟议的课程将在1-2年内完成。在第1-3年，将进行上述研究，并将利用这些数据准备R01拨款申请。在人类中，牙周完整性的丧失导致牙周破坏被称为牙周炎。众所周知，牙周炎是由易感宿主中的特定牙周病原体引发的。然而，这些微生物破坏细胞-基质相互作用调节的机制尚不清楚。调节这些相互作用的蛋白质统称为基质细胞分子。该研究计划的目标是研究Periostin，一种新的基质细胞分子和牙周膜标记物，在牙周健康和疾病中的重要性。我们已经证明，随着时间的推移，Periostin缺失的小鼠会遭受严重的牙槽骨丢失，导致牙齿脱落。我们假设，在牙周病期间，周围素水平降低，导致宿主对牙周破裂的易感性增加。这一发现的临床验证是根本的，因为它可能会触发创新解决方案的开发，最终将帮助患者。拟议的职业发展计划旨在确保有足够的时间来实现两个主要目标：1)获得将基于实验室的研究结果转化为临床研究的额外培训，包括进一步的统计培训和资质；2)利用收集的数据和新开发的临床研究专业知识，使他成为未来以患者为导向的研究的独立调查者奖的合格候选人。该项目将使Rios博士能够进一步探索Periostin和牙周疾病之间的可能关系，这是开发人类临床试验所必需的。 公共卫生相关性：产生的数据将对我们在细胞-基质动态及其在牙周动态平衡中的作用的牙周生物学的理解有重要的影响。这些研究可能会突出确定牙周病易感性的新途径，这些途径可以作为治疗炎症性牙周病的靶点。

DESCRIPTION (provided by applicant): The candidate's background in Oral and Molecular Biology as well as his training in Periodontics equips him with the tools to explore innovative approaches to understand and address clinically relevant health problems. The training and the research proposed in this application are designed to increase his investigating skills to translate important laboratory findings into the clinical arena, with the ultimate goal of developing into an independent clinical and translational scientist. In the Years 1-2, the proposed curriculum will be completed. In Years 1-3, the research described will be conducted and the data will be utilized to prepare an R01 grant application. In humans, loss of periodontal integrity leading to periodontal destruction is known as periodontitis. It is known that periodontitis is triggered by specific periodontal pathogens in a susceptible host. However, the mechanism by which these microorganisms compromise the modulation of cell-matrix interactions is not clearly understood. The proteins modulating these interactions are known collectively as matricellular molecules. The goal of the research proposal is to study the importance of Periostin, a novel matricellular molecule and periodontal ligament marker, in periodontal health and disease. We have shown that Periostin null mice suffer severe alveolar bone loss over time resulting in tooth loss. We hypothesize that Periostin levels are decreased during periodontal disease, leading to increased host susceptibility to periodontal breakdown. The clinical validation of this finding is fundamental as it may trigger the development of innovative solutions that will ultimately help the patients. The proposed career development plan is designed to secure sufficient time to achieve two main objectives: 1) to gain additional training in the translational application of laboratory based research findings to clinical research, including further statistical training, and grantsmanship; and 2) to use the data collected and newly developed clinical research expertise to position him as a qualified candidate for a future independent investigator award in patient-oriented research. This project will allow Dr. Rios to further explore the possible relationship between Periostin and periodontal disease necessary for the development of human clinical trials. PUBLIC HEALTH RELEVANCE: The data generated will have important implications for our understanding of periodontal biology in the context of cell-matrix dynamics and their role in periodontal homeostasis. These studies may highlight novel pathways that determine periodontal disease susceptibility that could be targeted in the treatment of inflammatory periodontal diseases.