Anatomic variations in muscle gene expression
肌肉基因表达的解剖学变异
基本信息
- 批准号:7197256
- 负责人:
- 金额:$ 16.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-04-06 至 2010-02-28
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnatomyAnimal ModelAttentionBiochemistryChildhoodClassificationComplexDYSF geneDataDystrophinEnvironmentFunctional disorderGene ExpressionGene ProteinsGene-ModifiedGenesGeneticGenomicsHistologicHumanIndividualKnowledgeLaboratoriesLimb-Girdle Muscular DystrophiesLocalizedMapsMembraneMentorsMolecularMolecular ProfilingMusMuscleMuscle FibersMuscular DystrophiesMutationMyopathyNeurologistNeuromuscular DiseasesPathogenesisPhenotypePhysiciansProcessProteinsRangeResearch PersonnelResearch Project GrantsSarcolemmaScientistSkeletal MuscleSpecimenTechniquesTherapy Clinical TrialsTrainingVariantdesigndisease phenotypehuman diseasemouse modelprogramsrepairedresponse
项目摘要
DESCRIPTION (provided by applicant):
The candidate is a pediatric neurologist specializing in neuromuscular diseases who wishes to acquire the training needed to become an independent physician scientist. He plans to study the pathophysiology of the muscular dystrophies and take courses in genomics and biochemistry. The environment consists of mentors, colleagues, and collaborators who have the expertise needed for such training, as well as a well equipped laboratory. The candidate hopes to use genomic techniques to correlate animal models to human disease and identify targets for the pharmacologic treatment of neuromuscular diseases. The research project addresses the selective involvement of different skeletal muscles in the muscular dystrophies. This finding has long remained unexplained, and cannot be attributed solely to anatomic or histologic features. Gene expression techniques and divergent phenotypes among the dysferlinopathies provide a new means of approaching this question. The overall hypothesis is that differences between muscles at the molecular level are related to their varying responses to genetic insults; these differences will be examined in both normal and dysferlin-deficient muscle. Aim 1 is to create a molecular map of human skeletal muscle groups using gene expression analysis. The resulting data will be compared to that already available for mouse muscles; the interspecies correlation will assist in the interpretation of therapeutic trials in mice. Aim 2 is to identify gene expression differences between muscle specimens obtained from individuals displaying two different phenotypes of dysferlin deficiency, limb girdle muscular dystrophy 2B and Miyoshi myopathy. Aim 3 is to perform analyses on the protein products of genes identified in Aims 1 and 2 to determine associations with dysferlin and dystrophin. Proteins that are determined to interact with dysferlin and dystrophin may be potentially targets for pharmacologic therapies.
描述(由申请人提供):
候选人是一名儿科神经学家,专门研究神经肌肉疾病,希望获得成为独立医生科学家所需的培训。他计划研究肌肉萎缩症的病理生理学,并学习基因组学和生物化学课程。该环境由具有此类培训所需专业知识的导师,同事和合作者以及设备齐全的实验室组成。候选人希望利用基因组技术将动物模型与人类疾病联系起来,并确定神经肌肉疾病药物治疗的靶点。该研究项目解决了不同骨骼肌在肌营养不良症中的选择性参与。这一发现长期以来一直无法解释,不能仅仅归因于解剖或组织学特征。基因表达技术和dysferlinopathies中不同的表型提供了解决这个问题的新方法。总体假设是,在分子水平上的肌肉之间的差异与它们对遗传损伤的不同反应有关;这些差异将在正常和dysferlin缺乏的肌肉中进行检查。目的1是利用基因表达分析建立人类骨骼肌群的分子图谱。将所得数据与小鼠肌肉的现有数据进行比较;种间相关性将有助于解释小鼠治疗试验。目的2是确定从表现出两种不同表型的dysferlin缺乏症、肢带型肌营养不良症2B和三好肌病的个体获得的肌肉样本之间的基因表达差异。目的3是对目的1和2中鉴定的基因的蛋白产物进行分析,以确定与dysferlin和dystrophin的关联。确定与dysferlin和dystrophin相互作用的蛋白质可能是药物治疗的潜在靶点。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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PETER B. KANG其他文献
PETER B. KANG的其他文献
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{{ truncateString('PETER B. KANG', 18)}}的其他基金
Foundations for a Phase 1 Clinical Trial ofCell-based Therapy for Duchenne Muscular Dystrophy
杜氏肌营养不良症细胞疗法一期临床试验的基础
- 批准号:
10517066 - 财政年份:2022
- 资助金额:
$ 16.81万 - 项目类别:
Foundations for a Phase 1 Clinical Trial ofCell-based Therapy for Duchenne Muscular Dystrophy
杜氏肌营养不良症细胞疗法一期临床试验的基础
- 批准号:
10665798 - 财政年份:2022
- 资助金额:
$ 16.81万 - 项目类别:
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