This proposal for a Mentored Patient-Oriented Research Career Development Award (K23) application is divided into didactic, applied clinical and translational research components. The didactic component will provide educational experiences to allow the principal investigator to design, conduct, and analyze patient-oriented research. A detailed instructional plan is described in the application. The clinical and translational research training component will provide the candidate an opportunity to work closely with experienced clinical and basic science investigators. The project will combine 1) in vivo, retrospective assessment of the severity of any postradiation dental lesions as related to factors such as radiation field parameters, the radiation dose to which teeth were exposed, and the use of salivary gland radiation protector drugs; 2) in vitro chemical, mechanical, and morphologic analyses of structure and properties of in vivo irradiated teeth as compared to non-irradiated teeth; 3) the structure/property relationships will be used in finite element modeling of the stress distribution within irradiated teeth under simulated functional loading conditions; 4) developing the infrastructure and acquiring the preliminary data to continue the investigation as a prospective, longitudinal clinical trial for future grant applications in order to correlate the initiation and progression of post-radiation dental lesions to additional clinical factors such as xerostomia and occlusal patterns, as well as radiation dose, field parameters, and the use radiation protector drugs. This project will enable the candidate to obtain research skills in the following areas: 1) retrospective and prospective methodology in the clinical evaluation of patient factors related to therapeutic radiation-induced dental lesions; 2) laboratory evaluation of the associated changes in the structure and properties of teeth exposed to therapeutic radiation; 3) finite element calculation and modeling of stress distribution patterns that develop in these teeth under simulated functional loading. By completing the objectives outlined in the project, Dr. Walker will develop skills necessary to function as an independent clinical researcher and have the opportunity to collaborate with basic scientists to gain insight into how laboratory analyses can be incorporated into patient-based investigations. A key strength of this project is the associated feedback mechanism that relates the clinical problem to both clinical and laboratory data, the integration of scientific principles into clinical practice.