The Administrative Core of the Center for SUDEP Research

 描述（由申请人提供）：新出现的证据表明，脑干介导的心血管和呼吸过程中存在一种深刻的、有害的、由癫痫驱动的脑桥上效应的“完美风暴”，导致癫痫患者意外猝死（SUDEP）。这种致命的失调可能是由结构（预先存在的癫痫发作-受损的自主调节区域）和功能（神经递质/神经调质）倾向支持的。一个多学科的中心无墙（CWW），系统生物学为基础的方法，组装和利用临床，电生理学，生物化学，成像，遗传学和神经病理学的专业知识，最有可能解开SUDEP机制和作用的脑桥上的影响。NINDS通过探索性赠款1 P20-NS 076965资助了SUDEP死亡率的预防和风险识别（PRISM）项目。SUDEP转化研究联盟（SUTRA）是PRISM的下一阶段，是一个由凯斯西储大学领导的多中心、多学科联盟，包括加州大学洛杉矶分校、芝加哥西北大学、纽约大学、南伊利诺伊大学、俄勒冈州传统研究所、伦敦大学学院、北德克萨斯大学和哥伦比亚大学。PRISM已经建立了基础设施、资源和协议，并建立了遗传学（203个SUDEP DNA样本）、神经病理学（139个SUDEP大脑）和多模式癫痫发作数据库，这些数据库对超过300名前瞻性调查的患者进行了研究。我们已经生成了初步的遗传，神经病理学和生理癫痫发作数据，以利用该应用程序的假设驱动的科学项目。SUTRA行政核心的主要使命是监督、协调、优先安排和促进CWW的研究活动和运作。 该组织计划将包括一个信息学和数据分析核心和五个科学项目U 01。SUTRA的具体目标是：1）通过制定和实施SUTRA章程以及定期审查和修订方向，在CWW的研究、发现和传播新知识的使命中提供全面领导、愿景、专业知识和方向，2）促进核心与参与SUTRA的研究小组之间的沟通和合作，3）向NINDS、执行委员会和指导委员会报告中心的所有活动和进展; 4）进一步发展和扩大SUTRA研究基础设施（扩大其生物储存库，建立试点和可行性计划，导师计划和丰富计划，以促进对最新研究趋势和机会的认识）。SUTRA将优化和简化与当地资源和国家资源的接口，包括Epi 4K，自闭症脑网络，北美SUDEP登记处，SUDEP研究所和儿童猝死计划。

 DESCRIPTION (provided by applicant): Emerging evidence points to a "perfect storm" of profound, deleterious, seizure-driven suprapontine effects on brainstem-mediated cardiovascular and respiratory processes leading to Sudden Unexpected Death in Epilepsy (SUDEP). This fatal dysregulation is likely to be underpinned by structural (pre-existing seizure- damaged autonomic regulatory areas) and functional (neurotransmitter/neuromodulator) predispositions. A multi-disciplinary Center Without Walls (CWW), systems biology-based approach that assembles and leverages clinical, electrophysiological, biochemical, imaging, genetic and neuropathological expertise has the best potential to unlock SUDEP mechanisms and the role of suprapontine influences. The NINDS funded the Prevention and Risk Identification of SUDEP Mortality (PRISM) Project through exploratory grant 1P20- NS076965. The SUDEP Translational Research Alliance (SUTRA) is the next phase of PRISM and is a multi-center, multi-disciplinary consortium led by Case Western Reserve University and includes UCLA, Northwestern University in Chicago, New York University, Southern Illinois University, Legacy Research Institute, Oregon, University College London, University of North Texas and Columbia University. PRISM has built infrastructure, resources and protocols, and established genetics (203 SUDEP DNA samples), neuropathology (139 SUDEP brains) and multimodal seizure data repositories on >300 prospectively surveyed patients. We have generated preliminary genetic, neuropathology and physiological seizure data to leverage the hypothesis driven scientific projects of this application. The primary mission of the SUTRA Administrative Core is to oversee, co-ordinate, prioritize and facilitate CWW research activities and functioning. The organized plan will comprise an Informatics and Data Analytics Core and five scientific project U01s. Specific Aims for SUTRA are 1) to provide overall leadership, vision, expertise and direction in the CWW's mission of research, discovery and dissemination of new knowledge, through establishment and implementation of the SUTRA charter and regular review and revision of direction, 2) to facilitate communications and collaborations between Cores and research groups participating in SUTRA, 3) to report all Center activities and progress to NINDS, the Executive and Steering Committees and 4) to further develop and expand SUTRA research infrastructure (expanding its biorepositories, establishing a Pilot and Feasibility Program, a Mentorship Program and an Enrichment Program to foster awareness of the latest research trends and opportunities). SUTRA will optimize and streamline interfaces with local resources and national resources including Epi4K, Autism Brain Net, the North American SUDEP Registry, the SUDEP Institute and the Sudden Death in Childhood Program.