INBRE: MUSC: ENHANCEMENT OF BIOENGINEERING PROGRAM AT MUSC

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 MUSC致力于INBRE网络的成功，并将在需要时通过再生医学与细胞生物学系提供机构支持，以补充核心设施的INBRE资金（详见本竞争性更新申请的G部分）和指导，目标教师试点（种子）项目。该计划在向联邦和私人机构提交多项赠款方面发挥了重要作用。再生医学系将分配足够的机构支持，以确保目标教师有保护的时间所要求的NCRR准则，全职技术人员和用品足以支付动物和其他费用。与目前的SC INBRE赠款一样，目标教师将免费完全访问所有INBRE和COBRE核心。每个试点项目的教员都将有一个目标导师，并将参加代表COBRE和INBRE目标教员组织的每月辅导会议。每年征求试点项目，并由全球COBRE导师（Tom博格博士、Richard Swaja博士、Martin Morad博士）以及Markwald博士和Argraves博士组成的指导小组进行审查。为了竞争一个试点项目，需要一个具体的4页建议书，格式如Ghatak博士的项目所示，新SC INBRE第一年的目标项目。所有项目都基于再生医学主题，直接与“发现周期”格式相关。对于后者，我们指的是从鉴定患有心脏发育（出生）缺陷或成人心血管疾病（例如二尖瓣脱垂）的患者群体中的基因开始的周期。一旦基因被识别，动物或培养模型建立，以了解机制和潜在的治疗目标。药理学或分子方法用于确定抑制或刺激潜在靶点是否会改变疾病的进展或结果。然后建立转化试验以在人类患者群体中测试药理学试剂，从而完成周期。发现周期的一个范例是氯沙坦治疗马凡氏综合征，这是通过鉴定基因突变（tumin）、其机制和治疗靶点（TGF β信号传导）来确定的。SC INBRE的竞争性更新申请中描述的试点项目是基于这样的发现，即基质细胞蛋白CCN 1突变时会导致儿童不同程度的人类房室间隔缺损或瓣膜病变。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. MUSC is committed to the success of the INBRE network and will provide institutional support through the Department of Regenerative Medicine & Cell Biology, when needed, to supplement INBRE funding of core facilities (detailed in Section G of this competitive renewal application) and mentored, target faculty pilot (seed) projects. This program has been instrumental in developing multiple grant submissions to both federal and private agencies. The Department of Regenerative Medicine will allocate sufficient institutional support to assure that target faculty have protected time as required by the NCRR guidelines, a full time technician and supplies sufficient to cover animal and other costs. As in the current SC INBRE grant, target faculty will have full access without cost to all INBRE and COBRE cores. Each pilot project faculty person will have a target mentor and also will be expected to participate in monthly mentoring sessions organized on behalf of COBRE and INBRE target faculty. Pilot projects are solicited annually and reviewed by a mentoring team of global COBRE mentors (Drs. Tom Borg, Richard Swaja, Dr. Martin Morad) and both Drs. Markwald and Argraves. To compete for a pilot project, a specific 4 page proposal is required, in the format shown in Dr. Ghatak's project, target project for year one of the new SC INBRE. All projects have been based on a regenerative medicine theme that directly can be related to a "Cycle of Discovery" format. By the latter, we mean a cycle that starts with the identification of genes in a patient population with either a cardiac developmental (birth) defects or an adult cardiovascular disease (e.g. mitral valve prolapse). Once the gene is identified, animal or culture models are established to understand mechanisms and potential therapeutic targets. Pharmacological or molecular approaches are used to determine if inhibiting or stimulating potential targets modifies progression or outcome of the disease. Translational trials are then set up to test the pharmacological agent in human patient populations, thus completing the cycle. A paradigm for the cycle of discovery would be losartan treatment for Marfan's syndrome, which was determined by identifying the genetic mutation (fibrillin), its mechanism and a therapeutic target (TGF beta signaling). The pilot project described in this competitive renewal application for SC INBRE is based on the finding that a matricellular protein, CCN1, when mutated, causes human atrioventricular septal defect or valve lesions to varying degrees in children.