PLANNING INTERDISCIPLINARY STUDIES OF DIABETIC HEART: TRANSLATIONAL & CLINICAL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。预计转化研究和临床实施途径将转化和转移基础发现途径的输出，形成从实验室到床边的连续体。翻译和临床实施都将在人体中进行。它们将涉及下列要素：o根据特定的基因型和表型标准对患者分组（一般为20-30人）进行小规模研究，以检验基础发现途径产生的科学假设；o建立生物标志物、基因型、和表型特征，确定患者选择和分层的最佳标准，通过生物标志物状态选择的患者群体中的概念验证研究，用于预测所建议的预防/治疗策略的有效性的更大规模结果。规划过程将涉及开发方法，将发现产品从动物模型转化为技术平台上的人类。总体规划模板将包括两个阶段的过程，以评估和验证发现路径科学家发现的生物标志物。首先，严格的表型策略将被设计用于小群体的研究，以评估分子、生化和成像生物标志物在检测疾病方面的潜在效用。例如，该小组将解决将在动物模型中开发的复杂成像方法转化为实际人类应用的计划，例如心脏代谢成像以识别有心肌病风险的个体糖尿病患者或纳米颗粒引导策略以检测易损的动脉粥样硬化斑块。其次，在第一阶段研究后显示出希望的生物标志物将在国家人口结果研究中得到验证。在某些情况下，设想开发替代标记是必要的。最后，将建立一个生物标志物小组（糖尿病心血管生物标志物小组或DCBP）的生成策略。预计DCBP在发现早期疾病、提供风险分层或评估新疗法方面的应用将最终进行前瞻性评估。以下11个研究学科将包括转化研究和临床实施计划小组的初始成员：人类心血管生理学和病理生理学、人类内分泌学和中间代谢学、成像科学、成像物理学、人类遗传学和药物遗传学、生物统计学、计算生物学、放射化学、生物工程、生物医学伦理学和人口统计学

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