A MULTILEVEL APPROACH TO ENERGY BALANCE AND CANCER ACROSS THE LIFECOURSE

项目总结（见说明）： 利用圣路易斯华盛顿大学教师的广泛科学专业知识以及来自其他机构的合作者和顾问，我们建议建立在现有的跨学科方法的基础上，并创建一个中心，以解决肥胖和癌症的机制，“从细胞到社会”。我们包括超越传统的风险因素癌症协会的项目，看看多层次和多代协会以及传统的癌症风险行为的相互作用。我们利用密苏里州提供的独特机会来研究人口，因为它具有种族/民族的多样性， 社会经济地位。我们将描述孕前饮食，营养和建筑环境政策影响不活动，身体活动和能量平衡的机制，以影响整个生命过程中的体重和致癌作用。具体而言，我们的目标是： 1.在小鼠模型中研究母体高脂肪饮食和代谢生物能量学变化对雄性小鼠后代前列腺发育和前列腺癌易感性的影响; 2.研究体力活动和肥胖在膀胱切除术后排尿和性功能中的作用; 3.以非霍奇金淋巴瘤为初始平台，结合风险和死亡率的生物、临床和社会决定因素，开发跨生命过程和世代的肥胖模型，可应用于不同的癌症结果; 4.研究影响能量平衡和肥胖的营养和建筑环境相关政策; 5.在跨学科的环境中培养博士后研究员，从事能量学和癌症的职业，并使我们大学的学者接触肥胖和癌症的跨学科工作; 6.通过建立在中心主题和资源基础上的小规模创新跨学科研究促进科学协同作用; 7.通过建立一个由优秀的行政，预算和技术资源支持的杰出的跨学科中心，最大限度地提高TREC相关研究和核心的效率和生产力。 为了实现这些目标，我们提出了四个研究项目和五个核心，形成一个有凝聚力的， 跨学科中心侧重于研究、培训/职业发展和传播。

PROJECT SUMMARY (See instructions): Drawing on the broad scientific expertise of faculty at Washington University in St. Louis and collaborators and consultants from other institutions, we propose to build on existing transdisciplinary approaches and create a center to address mechanisms of obesity and cancer, "from cell to society". We include projects that move beyond traditional risk factor-cancer associations to look at multilevel and multigenerational associations as well as the interaction of traditional cancer risk behaviors. We leverage the unique opportunity Missouri provides to study human populations given its diversity across race/ethnicity and socioeconomic status. We will delineate mechanisms by which preconception diet, nutrition & built environment polices impact inactivity and physical activity and energy balance to influence body weight and carcinogenesis across the life course. Specifically we aim to: 1. Investigate in a mouse model the effect of maternal high fat diet and changes in metabolic bioenergetics on prostate gland development and susceptibility to prostate cancer in male mouse offspring; 2. Study the role of physical activity and obesity in post-prostatectomy urinary and sexual function; 3. Develop models of obesity across the life course and generations incorporating biologic, clinical and social determinants of risk and mortality, which can be applied to different cancer outcomes, using non-Hodgkin Lymphoma as the initial platform; 4. Study policies relating to nutrition and built environment that impact energy balance and obesity; 5. Train postdoctoral fellows in a transdisciplinary environment to pursue careers in energetics and cancer and expose scholars from across our university to transdisciplinary work in obesity and cancer; 6. Foster scientific synergy via smaller-scale innovative transdisciplinary research that builds on the Center's theme and resources; and 7. Maximize efficiency and productivity of TREC-related studies and cores by building an outstanding transdisciplinary center supported by outstanding administrative, budgetary, and technology resources. To address these aims, we propose four research projects and five cores that form a cohesive, transdisciplinary center focused on research, training/career development, and dissemination.