INBRE: MUSC: ENHANCEMENT OF BIOENGINEERING PROGRAM AT MUSC

INBRE：MUSC：加强 MUSC 的生物工程项目

• 批准号: 8360739
• 负责人: ROGER R MARKWALD
• 金额: $ 17.08万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360739
• 关键词: Adult; Animals; Biomedical Engineering; Biomedical Research; Cardiac; Cardiovascular Diseases; Cellular biology; Centers of Research Excellence; Child; Commit; Congenital Abnormality; Core Facility; Development; Disease Outcome; Faculty; Funding; Gene Mutation; Genes; Grant; Guidelines; Human; Lesion; Losartan; Marfan Syndrome; Mentors; Mitral Valve Prolapse; Modeling; Molecular; Mutate; National Center for Research Resources; Persons; Pilot Projects; Principal Investigator; Proteins; Regenerative Medicine; Research; Research Infrastructure; Resources; Seeds; Signal Transduction; Source; South Carolina; Testing; Time; Transforming Growth Factor beta; United States National Institutes of Health; atrioventricular septal defect; base; cost; fibrillin; patient population; programs; success; therapeutic target

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 MUSC致力于近型网络的成功，并将在需要时通过再生医学和细胞生物学部提供机构支持，以补充核心设施的近亲资金（此竞争性更新应用的G节中详细介绍），并进行了指导，目标教师试点（种子）项目。该计划有助于向联邦和私人机构开发多个赠款。再生医学系将分配足够的机构支持，以确保目标教师按照NCRR指南的要求，这是一名全职技术人员，并提供了足以支付动物和其他费用的供应。与当前的SC Inbre赠款一样，Target教职员工将完全访问，而无需全部近亲和cobre核心。每个试点项目教师都将有目标导师，并且还有望代表Cobre和Inbre Target教师参加每月的指导会议。飞行员项目每年都会征集，并由全球柯布尔指导者的指导团队（汤姆·博格博士，理查德·斯瓦贾，马丁·莫拉德博士）和两个博士进行审查。 Markwald和Argraves。为了竞争试点项目，需要以Ghatak博士的项目为“新SC Inbre”中的目标项目的格式进行特定的4页建议。所有项目均基于再生医学主题，该主题可以与“发现周期”形式直接相关。到后者，我们的意思是一个循环，该周期是从心脏发育（出生）缺陷或成人心血管疾病（例如二尖瓣脱垂）的患者人群中鉴定基因的。一旦确定了基因，就建立了动物或培养模型以了解机制和潜在的治疗靶标。药理或分子方法用于确定抑制或刺激潜在靶标是否会改变疾病的进展或结果。然后建立翻译试验以测试人类患者人群中的药理学剂，从而完成周期。发现循环的范例将是氯萨坦对马凡氏综合征的治疗，该治疗方法是通过鉴定遗传突变（原纤维素），其机制和治疗靶标（TGFβ信号传导）来确定的。在此竞争性更新应用中描述的SC INBRE的试点项目基于以下发现：当突变时，母细胞蛋白CCN1在儿童中导致人室室内间隔缺陷或瓣膜病变。