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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DE019872-04
Application #
8691407
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
King, Lynn M
Project Start
2010-07-02
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$131,003
Indirect Cost
$8,503
Name
University of Michigan Ann Arbor
Department
Dentistry
Type
Schools of Dentistry
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Lin, Zhao; Rios, Hector F; Cochran, David L (2015) Emerging regenerative approaches for periodontal reconstruction: a systematic review from the AAP Regeneration Workshop. J Periodontol 86:S134-52
Rios, Hector F; Bashutski, Jill D; McAllister, Bradley S et al. (2015) Emerging Regenerative Approaches for Periodontal Reconstruction: Practical Applications From the AAP Regeneration Workshop. Clin Adv Periodontics 5:40-46
Cochran, David L; Cobb, Charles M; Bashutski, Jill D et al. (2015) Emerging regenerative approaches for periodontal reconstruction: a consensus report from the AAP Regeneration Workshop. J Periodontol 86:S153-6
Padial-Molina, Miguel; Rodriguez, Juan C; Volk, Sarah L et al. (2015) Standardized in vivo model for studying novel regenerative approaches for multitissue bone-ligament interfaces. Nat Protoc 10:1038-49
Padial-Molina, M; Volk, S L; Rios, H F (2014) Periostin increases migration and proliferation of human periodontal ligament fibroblasts challenged by tumor necrosis factor -? and Porphyromonas gingivalis lipopolysaccharides. J Periodontal Res 49:405-14
Rios, H F; Bonewald, L F; Conway, S J (2014) Lessons from the matricellular factor periostin. J Dent Res 93:843-5
Padial-Molina, Miguel; Volk, Sarah L; Rodriguez, Juan C et al. (2013) Tumor necrosis factor-ýý and Porphyromonas gingivalis lipopolysaccharides decrease periostin in human periodontal ligament fibroblasts. J Periodontol 84:694-703
Padial-Molina, Miguel; Marchesan, Julie T; Taut, Andrei D et al. (2012) Methods to validate tooth-supporting regenerative therapies. Methods Mol Biol 887:135-48
Padial-Molina, M; Volk, S L; Taut, A D et al. (2012) Periostin is down-regulated during periodontal inflammation. J Dent Res 91:1078-84
Rios, Hector F; Lin, Zhao; Oh, Bina et al. (2011) Cell- and gene-based therapeutic strategies for periodontal regenerative medicine. J Periodontol 82:1223-37

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