2012 Notch Signaling in Development, Regeneration & Disease Gordon Conference

2012 发育、再生中的 Notch 信号传导

• 批准号: 8334175
• 负责人: RAPHAEL KOPAN
• 金额: $ 1万
• 依托单位: GORDON RESEARCH CONFERENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-13 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334175
• 关键词: Academia; Address; Adult; Aging; Alagille Syndrome; Alzheimer' s Disease; American; Animal Model; Antibodies; Area; Attention; Biochemistry; Biology; Boxing; CADASIL; Cancer Biology; Chronic; Clinical; Collaborations; Communication; Communities; Coupled; Development; Developmental Biology; Developmental Cell Biology; Disease; Drosophila genus; Drug Industry; Dysostoses; Education; Environment; Future; Genetic; Goals; Health; Heart Valves; Human; Industry; International; Leadership; Life; Location; Maine; Malignant Neoplasms; Mediator of activation protein; Memory; Multiple Sclerosis; Muscular Dystrophies; Natural regeneration; Nervous system structure; Notch Signaling Pathway; Onset of illness; Organ; Outcome; Participant; Pathology; Pathway interactions; Peptide Hydrolases; Postdoctoral Fellow; Reagent; Reliance; Research; Research Personnel; Scientist; Signal Pathway; Signal Transduction; Solutions; Stem cells; Students; Technology; Therapeutic; Thinking; Time; Tissues; Travel; Work; aortic valve disorder; base; body system; cancer initiation; cancer prevention; cancer therapy; cell type; college; cost; drug development; experience; frontier; gain of function; human disease; inhibitor/antagonist; interest; loss of function; malformation; meetings; notch protein; novel; secretase; symposium; tumor

DESCRIPTION (provided by applicant): The inaugural Notch Signaling in Development, Regeneration & Disease meeting, to be held August 12-17, 2012 at Bates College, Maine, will address an unmet need in the American scientific community, both academic and industrial. The broad and long-term goal of this conference is to enhance cross-disciplinary discussions and collaborations in this rapidly expanding field and to better address the myriad of mechanistic, developmental, organismal, clinical and therapeutic challenges met by practitioners in the field. The Notch signaling pathway is a central mediator of short-range inter-cellular communication in metazoans, under study since 1914 in Drosophila, in other model organisms since the 1980's, and in human health since 1991. Today it is confirmed that alterations in Notch activity underlie several developmental syndromes (Alagille, Spondylocostal Dysostosis, aortic valve disease), adult onset diseases (CADASIL, various heart and valve malformations, muscular dystrophy, multiple sclerosis) and cause or contribute to cancer initiation, promotion or progression in a tissue-dependent manner. These pathologies reflect both loss of function (e.g., Alagille, CADASIL) and gain of function (e.g., cancer). Because the Notch signaling pathway is unique in its reliance on proteases, in the paucity of signal modulators, and because it is repeatedly used in many organs throughout adult life, the road to chronic management of Notch signaling in disease is obscured by many untoward outcomes with available therapies. The main strategy currently practiced in anti-tumor campaigns is based on g-secretase inhibitors or antagonistic antibodies; however, due to their indiscriminate inhibition of Notch receptors in all organs these reagents proved to be toxic during chronic administration. Expanding the interest in this pathway beyond developmental biology and cancer prevention is the realization that a great hurdle in Alzheimer's disease research is the difficulty in developing reliable Notch-sparing g-secretase inhibitors capable of inhibiting APP cleavage. Solving these puzzles requires "outside the box" thinking. The Specific Aims for this interdisciplinary yet pathway-focused meeting is to bring together a diverse community of 150 scientists working in every model organism and on nearly every organ system from academia, biotech and the pharmaceutical industry. The participants represent diverse approaches to study Notch function in development, its biochemistry and genetics; this will further facilitate discovery and drug development efforts. The 40 speakers represent world leaders with vast institutional memory as well as late-breaking presentations. Significantly, the informal and confidential environment in Gordon conferences, and the time provided for informal interactions, will create a forum in which cutting edge technologies, ideas and discoveries can be freely exchanged, stimulating new ideas. Most importantly, GRC excels in integrating students, postdocs and investigators wishing to enter a new field, such as the study of this important signaling pathway. PUBLIC HEALTH RELEVANCE: The goal of the proposed Gordon Research Conference on Notch signaling in development, regeneration and disease is to provide a stimulating, international and cross disciplinary forum for the dissemination and discussion of new research, concepts and therapeutic opportunities at the forefront of Notch related biology. Alteration in Notch activity underlies or contributes to a growing list of developmental syndromes (Alagille, Spondylocostal Dysostosis, aortic valve disease), adult onset diseases (CADASIL, Alzheimer's disease, various heart and valve malformations, muscular dystrophy, multiple sclerosis) and cancers, expanding the interest in this pathway well beyond scientists interested in developmental and cell biology to those interested in stem cells, cancer biology and therapy. The meeting will bring together a diverse community of scientists working in every model organism and on nearly every organ system from academia, biotech and the pharmaceutical industry.

描述（由申请人提供）：首届Notch Signaling in Development、Regenesis & Denise会议将于2012年8月12日至17日在缅因州贝茨学院举行，将解决美国科学界学术界和工业界未满足的需求。本次会议的广泛和长期目标是加强这个快速扩展领域的跨学科讨论和合作，并更好地解决该领域从业者遇到的无数机械、发育、组织、临床和治疗挑战。 Notch 信号通路是后生动物中短程细胞间通讯的核心介质，自 1914 年以来一直在果蝇中进行研究，自 20 世纪 80 年代以来在其他模式生物中进行研究，自 1991 年以来在人类健康中进行研究。今天已证实，Notch 活性的改变是多种发育综合征（Alagille、脊椎肋骨发育不全、主动脉瓣疾病）、成人发病疾病（CADASIL、各种心脏和瓣膜疾病）的基础畸形、肌营养不良症、多发性硬化症）并以组织依赖性方式导致或促成癌症的发生、促进或进展。这些病理反映了功能丧失（例如 Alagille、CADASIL）和功能获得（例如癌症）。由于Notch信号通路的独特之处在于它对蛋白酶的依赖、信号调节剂的缺乏，并且由于它在成年后的许多器官中被重复使用，因此在疾病中对Notch信号通路进行长期管理的道路被许多不良后果所掩盖。可用的疗法。目前抗肿瘤的主要策略是基于g-分泌酶抑制剂或拮抗抗体；然而，由于这些试剂对所有器官中的 Notch 受体进行不加区别的抑制，因此在长期给药过程中被证明是有毒的。人们认识到阿尔茨海默病研究的一大障碍是难以开发出能够抑制 APP 裂解的可靠的、保留 Notch 的 g 分泌酶抑制剂，从而将人们对这一途径的兴趣扩展到发育生物学和癌症预防之外。解决这些难题需要“跳出框框”思维。这次跨学科但以途径为重点的会议的具体目标是汇集来自学术界、生物技术和制药行业的 150 名科学家，他们研究每种模式生物和几乎所有器官系统。参与者代表了研究Notch功能在发育、生物化学和遗传学方面的不同方法；这将进一步促进发现和药物开发工作。 40 位演讲者代表了拥有丰富机构记忆和最新演讲的世界领导人。值得注意的是，戈登会议的非正式和保密环境以及提供的非正式互动时间将创建一个可以自由交流尖端技术、想法和发现的论坛，激发新想法。最重要的是，GRC 擅长整合希望进入新领域（例如这一重要信号通路的研究）的学生、博士后和研究人员。 公共健康相关性：拟议的关于Notch信号在发育、再生和疾病中的戈登研究会议的目标是提供一个刺激性的、国际性的跨学科论坛，以传播和讨论Notch前沿的新研究、概念和治疗机会相关生物学。 Notch 活性的改变是越来越多的发育综合征（Alagille、脊椎肋骨发育不全、主动脉瓣疾病）、成人发病疾病（CADASIL、阿尔茨海默病、各种心脏和瓣膜畸形、肌营养不良、多发性硬化症）和癌症的基础或促成因素，对这条途径的兴趣远远超出了对发育和细胞生物学感兴趣的科学家，以及对干细胞、癌症生物学和治疗感兴趣的科学家。这次会议将汇集来自学术界、生物技术和制药行业的各个模型生物和几乎每个器官系统的不同科学家群体。