Center for Musculoskeletal Disease Research (CMDR)

项目摘要/摘要 骨质疏松症、骨关节炎、骨骼发育异常以及 恶性肿瘤，如多发性骨髓瘤和乳腺癌转移，都会对肌肉骨骼产生负面影响。 系统。这些疾病影响到相当大比例的美国人口的健康，并导致显著的 残疾和高昂的医疗保健费用，而且不断需要更好地了解其原因和 以支持开发更有效和耐受性更好的治疗方法。为应付这方面的需要，我们建议 建立和发展肌肉骨骼疾病研究的专题和多学科中心 在阿肯色大学医学科学(UAMS)。CMDR的科学主题是分子 以及肌肉骨骼疾病的遗传分析，以及将骨骼作为其疾病一部分的疾病 这一过程将导致对其原因的更好理解，并将支持新疗法的开发。我们的 研究这些条件的方法将利用最先进的方法来分析基因组 转录组，细胞和动物的遗传操作，以及骨骼表型。成功的关键 这一方法的目的是增加研究与科学研究相一致的研究人员的数量 通过发展初级调查员和招聘新的和已有的调查员，中心的主题。 我们将在肌肉骨骼研究的坚实基础上建立CMDR，并实施一个组织 和管理计划，以创建一个自给自足的生物医学研究卓越中心(目标1)。我们会 还为青年研究人员和支持提供多学科发展和独特的研究机会 他们达到了独立点(目标2)。最后，我们将通过以下方式创建多样化的高效调查团队 提供获取有效和有用的研究核心的途径，这些研究核心将为 UAMS及其附属机构的研究基础设施(目标3)。总体中心组织和 管理计划包括行政核心、三个研究核心和四个研究项目，由 有前途的初级调查员。行政核心将监督该中心的建立和运作， 三个研究核心，以及一个教师发展计划。整合互动的师资队伍建设 该计划将包括一个正式的指导计划，指导四名初级调查人员走向独立。Cmdr 研究核心包括一个遗传模型核心，它将使用尖端方法对基因进行操作 细胞和老鼠，一个骨组织和成像核心，将分析老鼠和人类的硬组织，以及一个 生物信息学核心，将分析由小鼠细胞的分子分析产生的大数据集 和人体样本。本组织和管理计划的成功实施将是长期的 建立一个自给自足的生物医学研究卓越中心，产生新的和重要的成果 从而为各种涉及肌肉骨骼系统的疾病提供更有效的治疗方法。

PROJECT SUMMARY/ABSTRACT Conditions such as osteoporosis, osteoarthritis, developmental abnormalities of the skeleton, as well as malignancies, such as multiple myeloma and breast cancer metastases, all negatively affect the musculoskeletal system. These conditions affect the health of a sizable percentage of the US population and lead to significant disability and substantial health care costs, and there is an ongoing need to better understand their causes and to support the development of more effective and well-tolerated therapies. To address this need, we propose to establish and develop a thematic and multidisciplinary Center for Musculoskeletal Disease Research (CMDR) at the University of Arkansas for Medical Sciences (UAMS). The scientific theme of the CMDR is that molecular and genetic analysis of musculoskeletal diseases, and conditions that involve the skeleton as part of their disease process, will lead to a better understanding of their causes and will support development of novel therapies. Our approach to studying these conditions will take advantage of state-of-the-art approaches to analyze the genome and transcriptome, the genetic manipulation of cells and animals, and skeletal phenotyping. A key to the success of this approach will be to increase the number of investigators whose research is aligned with the scientific theme of the Center via development of junior investigators and recruitment of new and established investigators. We will establish the CMDR on a strong foundation of musculoskeletal research and implement an Organization and Management Plan to create a self-sustaining Center of Biomedical Research Excellence (Aim 1). We will also provide multidisciplinary development and unique research opportunities to young investigators and support them to the point of independence (Aim 2). Lastly, we will create diverse teams of productive investigators by providing access to effective and useful research cores that produce significant and long-lasting benefits to the research infrastructure of UAMS and its affiliated institutions (Aim 3). The Overall Center Organization and Management Plan includes the Administrative Core, three research cores, and four research projects, led by promising junior investigators. The Administrative Core will oversee establishment and operation of the center, the three research cores, and a faculty development plan. The integrated and interactive faculty development plan will include a formal mentoring program that will guide four junior investigators to independence. The CMDR research cores include a Genetic Models Core that will use cutting-edge approaches to genetically manipulate cells and mice, a Bone Histology and Imaging Core that will analyze mouse and human hard tissues, and a Bioinformatics Core that will analyze the large datasets generated by the molecular analyses of cells from mouse and human samples. Successful implementation of this Organization and Management Plan will in the long-term lead to a self-sustaining Center of Biomedical Research Excellence that will generate novel and important results leading to more effective therapies for a variety of conditions that involve the musculoskeletal system.