MSKCC Pilot Center for Precision Disease Modeling

 描述(申请人提供)：在哺乳动物遗传学研究中，没有比人类疾病更广泛的话题了。人类已经描述了数以千计的疾病、紊乱和综合征，并通过基因组技术的进步，正在以更多的分子细节来描述这些疾病、障碍和综合征。现在，医学研究的一个根本挑战是开发和开发最相关和最具预测性的模型系统，以了解这种基因变异的生理影响，最终目标是改善患者的护理和治疗。在过去的二十年里，用于研究正常和疾病状态下的基因功能的方法范围已经急剧增加。然而，随着我们的知识深度的增长，我们的期望也在增长--无论是对概括人类状况的实验模型的准确性，以及它们可以应用于提出生物问题的速度和范围。MSKCC精密疾病建模试点中心就是为了迎接这一挑战而设立的，它将联合和扩展现有的基础设施和研究，以创建一个创新中心，能够有效地利用体内模型以及临床前和联合临床研究的基因组信息，以增强对疾病的理解和治疗。该中心将包括两个核心：一个由基因组、小鼠建模和小鼠医院单位组成的临床前/联合临床核心和一个生物信息学核心。这些高度整合的核心资源将用于支持作为试点项目的三个疾病建模单位，以说明和帮助磨练该中心的能力。每个疾病建模项目都解决了与疾病的理解和治疗相关的重大和创新的基础、翻译和临床问题，范围包括早衰综合征早期骨髓衰竭的机制基础、结直肠癌的分子起源和相关性，以及为急性白血病患者开发精确的治疗策略。MSKCC精确疾病建模试点中心的主要目标是：(1)协调和加强MSKCC正在进行的基因组学、计算和动物建模工作，以建立一个综合的精密疾病建模试点中心；(2)为中心的疾病建模单元提供技术基础设施和支持；以及(3)向MSKCC调查人员和纽约其他机构提供中心的能力。此外，该中心将与NIH和其他试点中心合作，利用资源实现最大的国家影响。总而言之，该中心将为实现人类基因组学的潜力提供蓝图，以指导开发可用于开发新的治疗方法来改善疾病的准确模型。

 DESCRIPTION (provided by applicant): There is no broader topic in mammalian genetic research than human disease. Literally thousands of human diseases, disorders and syndromes have been described and through advances in genome technologies, are being characterized in much greater molecular detail. Now, a fundamental challenge for medical research is to develop and exploit the most relevant and predictive model systems to understand the physiological impact of this genetic variation, with the ultimate goal of improving patient care and treatment. Already in the past two decades, the range of approaches used to study gene function in normal and diseased states has increased dramatically. However, as our depth of knowledge has grown so too have our expectations - both in the accuracy of experimental models to recapitulate human conditions, as well as the speed and scope at which they can be applied to ask biological questions. The MSKCC Pilot Center for Precision Disease Modeling was conceived to take up this challenge, and will unite and expand existing infrastructure and research to create an innovative center with the ability to effectively utilize genomic information in vivo models, and preclinical and co-clinical studies to enhance the understanding and treatment of disease. The Center will include two Cores: a Preclinical/Co-Clinical Core consisting of Genomic, Mouse Modeling, and Mouse Hospital Units and a Bioinformatics Core. These highly integrated core resources will be used to support three Disease Modeling Units that serve as pilot projects to illustrate and help hone the capabilities of the Center. Each of th Disease Modeling projects address significant and innovative basic, translational, and clinical questions relevant to the understanding and treatment of diseases, ranging from the mechanistic basis for early bone marrow failure in premature aging syndromes, the molecular origins and dependencies of colorectal cancers, and the development of precision treatment strategies for patients with acute leukemia. The major goals of the MSKCC Pilot Center for Precision Disease modeling are to: (1) Coordinate and enhance ongoing genomics, computational, and animal modeling efforts at MSKCC to produce an integrated Pilot Center for Precision Disease Modeling; (2) Provide technical infrastructure and support for the Center's Disease Modeling Units; and (3) Make available Center capabilities to MSKCC investigators and other NYC institutions. Additionally, the Center will work with the NIH and other pilot centers to leverage resources to achieve the greatest national impact. In summary, the center will provide a blueprint for realizing the potential of human genomics to guide the development of accurate models that can be use to develop novel therapies to ameliorate disease.