CASE Center for Transdisciplinary Research on Energetic*

描述（由申请人提供）： 能量学和癌症跨学科研究案例中心的总体目标是有组织和科学地确定的。从理论上讲，我们寻求1）在凯斯大学建立一个富有成效的，持久的能量学和癌症跨学科研究计划，2）为新的和建立的科学家提供试点项目支持和培训机会，他们可以对能量学，能量平衡及其与癌症相关的后果进行综合研究，从癌症的病因和预防到生存，和3）建立合作关系，研究人员在整个我们的大学和其他TREC中心和大学，最大限度地和协同利用资源，显着影响与肥胖和癌症相关的问题。 在科学上，我们将进行一系列基于机制的实验室、临床和人群研究，以确定预防和控制肥胖的目标，并切断肥胖与癌症之间的联系。科学目标由三个方案和两个试点项目确定，这些项目高度互动，并得到三个TREC核心设施和17个综合癌症中心核心设施的支持。项目1试图确定肠道肿瘤诱导效应和分子信号通路与高脂饮食和肥胖的独特品系的小鼠染色体置换，使他们易感或抵抗高脂饮食的肥胖效应。项目2将检查候选基因变异和单倍型，相关的生物标志物和胰岛素抵抗综合征相关的血清标志物，以了解胰岛素抵抗综合征，相关基因和饮食因素如何在人类结肠肿瘤的病因学中协同作用。项目3将调查在青春期的关键生命过渡期肥胖和代谢功能障碍的决定因素。这项研究将利用一个独特的人群队列，作为克利夫兰儿童睡眠和健康研究的一部分，并将研究睡眠表型和睡眠障碍作为肥胖及其与代谢功能障碍的关系的一个新的和重要的决定因素。 试点项目1将研究ER应激途径的作用，将肥胖的代谢应激与胰岛素抵抗的发展联系起来，其后果以及确定中断这些途径以预防肥胖健康后果的分子靶点。

DESCRIPTION (provided by applicant): The overall goals of the Case Center for Transdisciplinary Research on Energetics and Cancer are defined organizationally and scientifically. Organizationally, we seek 1) to establish a productive, durable program for transdisciplinary research on energetics and cancer at Case University, 2) to provide pilot project support and training opportunities for new and established scientists who can conduct integrative research on energetics, energy balance and their consequences relative to cancer across the continuum from cancer causation and prevention through survival, and 3) to establish collaborative relations with investigators throughout our university and at other TREC Centers and universities to maximally and synergistically utilize resources to significantly impact problems associated with obesity and cancer. Scientifically, we will conduct a spectrum of mechanism-based laboratory, clinical, and population-based studies to identify targets for prevention and control of obesity and interruption of the linkage between obesity and cancer. The scientific aims are defined by three programs and two pilot projects which are highly interactive and are supported by three TREC core facilities and by the 17 Comprehensive Cancer Center core facilities. Project 1 seeks to determine the intestinal tumor-inducing effect and molecular signaling pathways associated with high-fat diet versus obesity in unique strains of mice with chromosomal substitutions rendering them susceptible or resistant to the obesigenic effects of hig hfat diets. Project 2 will examine candidate gene variance and haplotype, associated biomarkers, and insulin-resistance syndrome related serum markers to understand how insulin-resistance syndrome, related genes and dietary factors work in concert in the etiology of human colon neoplasia. Project 3 will investigate determinants of obesity and metabolic dysfunction during the critical life-transition period of adolescence. This study will capitalize on a unique population cohort followed as part of the Cleveland Children's Sleep and Health Study and will investigate sleep phenotype and sleep disturbances as a novel and important determinant of obesity and its relation to metabolic dysfunction. Pilot Project 1 will investigate the role of ER stress pathways linking the metabolic stress of obesity to development of insulin resistance, its consequences and the identification of molecular targets for interrupting these pathways to prevent health consequences of obesity.