Clinical and Translational Studies in Muscle Disease

肌肉疾病的临床和转化研究

基本信息

批准号：
9905490
负责人：
CONRAD C WEIHL
金额：
$ 17.26万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9905490
关键词：
Academy American Animal Model Award Bioinformatics Biological Assay Biological Markers Biopsy Cell Line Cell model Cells Chalk Clinic Clinical Clinical Investigator Clinical Research Collection Complement DNA Dermal Development Disease Disease model Educational Status Faculty Family Fibroblasts Functional disorder Future Genes Genetic Genetic Diseases Genetic Predisposition to Disease Genotype Goals Grant Inclusion Bodies Infrastructure Inherited Laboratories Lead Learning Limb-Girdle Muscular Dystrophies Mentors Mentorship Midcareer Investigator Award in Patient-Oriented Research Modeling Morbidity - disease rate Muscle Muscle Weakness Muscular Dystrophies Myoblasts Myopathy Natural History Neurology Pathogenesis Pathogenicity Pathologic Patients Phenotype Physicians Postdoctoral Fellow Pre-Clinical Model Proteins Research Research Infrastructure Research Personnel Sarcomeres Scientist Series Serum Severities Students Therapeutic Intervention Time Tissues Training Training Support Translational Research Universities Washington base biobank career career development clinical infrastructure cohort disease phenotype exome sequencing experience genetic variant genome sequencing graduate student induced pluripotent stem cell interest medical schools mortality muscle form neuromuscular next generation novel patient oriented research programs repository skills stem cell differentiation symposium targeted sequencing therapeutic target transcriptome sequencing translational model translational study whole genome

项目摘要

The overarching goal of this K24 application is to further my development as a clinical investigator and support the training of future physician scientists. My patient oriented research interests relate to understanding the clinical, pathologic, genetic and pathomechanistic underpinnings of inherited and acquired forms of muscle weakness. With the support of this grant, I will continue to perform genetic discovery of patients with muscle disease, increase our biorepository and develop phenotypic assays to understand novel disease pathogenesis. In addition, I will increase my mentorship responsibilities of graduate students, resident physicians, fellows and junior faculty within the neuromuscular group and Department of Neurology at Washington University School of Medicine. Moreover, I will learn valuable skills related to whole genome sequencing, RNA sequencing and induce pluripotent stem cell differentiation. A K24 grant would protect 50% effort and relieve future clinical and administrative responsibilities. The two interrelated aims of this proposal are 1) Perform genetic discovery on patients with unresolved inherited and acquired myopathies using whole genome and RNA sequencing strategies. 2) Develop and phenotype iPSC derived myoblast models of inherited and acquired myopathies. These aims will be achieved utilizing our existing biorepository within the Washington University School of Medicine Neuromuscular Genetics Project and the acquisition of new patients and patient material. Support through a K24 Midcareer Investigator Award in Patient-Oriented Research would come at a critical time in my career as I solidify my independent research program and increase my availability to mentor graduate students, post- doctoral fellows, residents, neuromuscular fellows and junior faculty in translational myology. Upon completion of this award, I will have integrated clinical trainees into our existing translational research infrastructure and created a successful pipeline to generate the next generation of clinician-scientists focused on muscle diseases.

此 K24 应用程序的总体目标是进一步促进我作为临床医生的发展研究者并支持未来医师科学家的培训。我的以患者为导向的研究兴趣涉及了解临床、病理、遗传和病理机制遗传性和后天性肌肉无力的基础。在这个的支持下资助，我将继续对肌肉疾病患者进行基因发现，增加我们的研究生物储存库并开发表型分析以了解新的疾病发病机制。在此外，我将增加对研究生、住院医师、神经肌肉组和神经病学系的研究员和初级教师华盛顿大学医学院。此外，我将学习与整体相关的宝贵技能基因组测序、RNA测序和诱导多能干细胞分化。一个K24 拨款将保护 50% 的努力并减轻未来的临床和行政责任。这该提案的两个相互关联的目标是 1) 对患有以下疾病的患者进行基因发现使用全基因组和 RNA 测序解决未解决的遗传性和获得性肌病策略。 2) 开发遗传性和获得性的 iPSC 衍生的成肌细胞模型并进行表型分析肌病。这些目标将利用我们现有的生物样本库来实现华盛顿大学医学院神经肌肉遗传学项目及收购新患者和患者材料。通过 K24 职业生涯中期调查员奖提供支持以患者为导向的研究将在我职业生涯的关键时刻到来，因为我巩固了我的独立的研究计划，并增加我指导研究生、毕业后的机会转化肌肉学领域的博士研究员、住院医师、神经肌肉研究员和初级教师。完成该奖项后，我将把临床实习生纳入我们现有的转化研究基础设施，并创建了成功的管道来产生下一个一代临床医生科学家专注于肌肉疾病。