PLANNING INTERDISCIPLINARY STUDIES OF DIABETIC HEART: TRANSLATIONAL & CLINICAL

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is anticipated that the Translational Research and Clinical Implementation Pathway will translate and transfer output from the Fundamental Discovery Pathway forming a continuum from bench-to-bedside. Both translation and clinical mplementation will be conducted in humans. They will involve the following elements: o small-scale studies in groups of patients (generally numbering 20-30) stratified according to specific genotypic and phenotypic criteria to test scientific hypotheses generated by the Fundamental Discovery Pathways o establishing relevant databases with biomarker, genotype, and phenotype characteristics o determining the optimal criteria for patient selection and stratification o proof-of-concept studies in patient populations selected by biomarker status o larger scale outcomes powered to predict efficacy of proposed prevention/treatment strategies The planning process will involve the development of approaches to translate discovery products from animal models to umans on the Technology Platform. The general planning template will involve a two-stage process to evaluate and validate biomarkers identified by the Discovery Pathway scientists. First, rigorous phenotyping strategies will be devised for studies in small groups of humans to assess the potential utility of molecular, biochemical and imaging biomarkers to detect disease. For example, the group will address plans for transforming sophisticated imaging approaches developed in animal models into practical human application such as metabolic imaging of the heart to identify the individual diabetic at risk for ardiomyopathy or nanoparticle-guided strategies to detect the vulnerable atherosclerotic plaque. Second, biomarkers that show promise following the first phase studies will be validated in national population outcomes studies. In some cases, it is envisioned that the development of surrogate markers will be necessary. Finally, strategies for the generation of a panel of biomarkers (the Diabetic Cardiovascular Biomarker Panel or DCBP) will be established. It is envisioned that the utility of the DCBP to detect early disease, provide risk stratification, or evaluate novel therapies will ultimately be evaluated in prospective. The following eleven research disciplines will comprise the initial membership of the Translational Research and Clinical Implementation planning group, Human Cardiovascular Physiology and Pathophysiology, Human Endocrinology and Intermediary Metabolism, Imaging Sciences, Imaging Physics, Human Genetics and Pharmaeogeneties, Biostatisties, Computational Biology, Radiologieal Chemistry, Bioengineering, Biomedical Ethics, and Population S