Clinical and Translational Studies in Muscle Disease

这个K24应用程序的首要目标是促进我作为临床医生的发展 研究人员和支持对未来内科科学家的培训。我的以病人为中心的研究 兴趣涉及了解临床、病理、遗传和病理机制。 遗传性和获得性肌肉无力的基础。在这个支持下 格兰特，我将继续执行肌肉疾病患者的基因发现，增加我们的 生物信息库和发展表型分析以了解新的疾病发病机制。在……里面 此外，我将增加我对研究生、住院医生、 神经肌肉组和神经内科的研究员和初级教员 华盛顿大学医学院。此外，我还将学习与整体有关的宝贵技能 基因组测序、RNA测序和诱导多潜能干细胞分化。又名K24 Grant将保护50%的努力，并减轻未来的临床和管理责任。这个 这项提议的两个相互关联的目标是：1)对患有 使用全基因组和RNA测序技术研究未解决的遗传性和获得性肌病 战略。2)遗传性和获得性成肌细胞模型的建立和表型 肌病。这些目标将利用我们现有的生物资源库在 华盛顿大学医学院神经肌肉遗传学项目及其收购 新病人和病人材料。通过K24职业中期调查员奖提供支持 以病人为本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 独立研究计划，并增加我指导研究生的机会，后 翻译肌学博士研究员、住院医师、神经肌肉研究员和初级教员。 在完成这个奖项后，我将把临床实习生整合到我们现有的 翻译研究基础设施，并创建了一条成功的管道来生成下一个 一代临床医生和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.