Clinical and Translational Studies in Muscle Disease

此K24应用程序的首要目标是进一步发展我的临床 研究人员和支持未来的医生科学家的培训。我的病人导向研究 兴趣涉及了解临床，病理，遗传和病理机制 肌肉无力的遗传和后天形式的基础。有了这个支持 授予，我将继续执行肌肉疾病患者的基因发现，增加我们的 生物贮藏库和发展表型分析，以了解新的疾病发病机制。在 此外，我将增加我的导师责任的研究生，住院医师， 神经肌肉组和神经病学系的研究员和初级教员， 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。K24 补助金将保护50%的努力，并减轻未来的临床和行政责任。的 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测序的未解决的遗传性和获得性肌病 战略布局2)开发和表型iPSC衍生的遗传和获得性成肌细胞模型 肌病这些目标将利用我们现有的生物储存库来实现。 华盛顿大学医学院神经肌肉遗传学项目和收购 新病人和病人的材料。通过K24中期职业研究者奖提供支持， 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，并增加我的可用性，指导研究生，后 博士研究员、住院医生、神经肌肉研究员和转化肌学初级教员。 在完成这项奖励后，我将把临床实习生融入我们现有的 转化研究基础设施，并创造了一个成功的管道，以产生下一个 一代临床科学家专注于肌肉疾病。

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.