Biomarkers for Therapy of FSHD (U54)

描述（由申请人提供）：我们的U54 Wellstone MD CRC的总体目标是追求基于生物标志物的研究策略，这将进一步加深我们对FSHD肌无力的潜在病理生理学的理解，并能够开发用于治疗FSHD的动物模型和治疗技术。我们研究的核心是大量来自FSHD家族的有据可查的生物材料，这使得对FSHD的潜在分子病理生理学和负责该疾病临床变异性的疾病修饰剂的统计学研究成为可能。这个生物储存库将扩大到包括血液，肌肉和衍生的肌肉祖细胞从个人有和没有家族病史的疾病沿着与一级亲属谁是经典的影响和那些没有FSHD等位基因作为对照，作为资源的FSHD研究人员在世界各地和三个相互关联的，合作中心的项目。中心项目将利用基因组测序、深度测序RNAseq和DNA甲基化技术来鉴定遗传和表观遗传修饰剂，并鉴定与FSHD疾病病理和进展相关的疾病生物标志物。FSHD的新型人源化小鼠和斑马鱼模型将被利用以更好地理解FSHD疾病病理学并开发疾病特异性疗法，包括基因和吗啉代疗法。中心项目将由7名互动研究人员及其合作者组成的重组小组进行，他们在临床医学，遗传学，分子和细胞生物学以及计算生物学和基因组学方面具有互补的专业知识。一个教育和培训核心将提供FSHD临床和基础研究的实践研究经验。一个行政核心将与我们的主要患者倡导小组FSH协会合作，定期组织WebX会议数据共享会议，FSHD研讨会，患者研究人员网络会议，以及中心研究人员，学员，NIH和中心咨询委员会的年度务虚会，以审查当前的进展并制定FSHD治疗的新方向。

DESCRIPTION (provided by applicant): The overarching goal of our U54 Wellstone MD CRC is to pursue a biomarker-based research strategy that will further our understanding of the underlying pathophysiology of FSHD muscle weakness and enable development of animal models and therapeutic technologies for treatment of FSHD. Central to our research is a large repository of well-documented biomaterials from FSHD families, making possible statistically powered studies of the underlying molecular pathophysiology of FSHD and disease modifiers responsible for the clinical variability of this disease. This biorepository will be expanded to include blood, muscle and derived muscle progenitor cells from individuals with and without family history of disease along with 1st degree relatives who are classically affected and those without the FSHD allele as controls, to serve as resource for FSHD researchers worldwide and for three inter-related, collaborative Center projects. Center projects will utilize-state-of-the at genome sequencing, deep sequencing RNAseq and DNA methylation technologies to identify genetic and epigenetic modifiers and to identify disease biomarkers related to FSHD disease pathology and progression. Novel humanized mice and zebrafish models of FSHD will be exploited to better understand FSHD disease pathology and to develop disease specific therapies including gene and morpholino therapies. Center projects will be pursued by a reorganized group of 7 interactive investigators and their collaborators with complementary expertise in clinical medicine, genetics, molecular and cellular biology, and computational biology and genomics. An Educational and Training Core will provide hands-on research experience in FSHD clinical and basic research. An Administrative Core will partner with our primary patient advocacy group, the FSH Society, to organize regular WebX conferencing data-sharing meetings, FSHD workshops, patient-researcher networking meetings, and an annual retreat for Center investigators, trainees, NIH and the Center Advisory Committee to review current progress and develop new directions towards therapeutics for FSHD.