2012 Notch Signaling in Development, Regeneration & Disease Gordon Conference

描述（由申请人提供）：将于2012年8月12日至17日在缅因州贝茨学院举行的首届Notch Signaling in Development，Regeneration & Disease会议将解决美国科学界学术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跨学科的讨论和合作，在这一迅速扩大的领域，并更好地解决无数的机械，发展，有机体，临床和治疗的挑战，在该领域的从业者遇到。Notch信号通路是后生动物中短距离细胞间通讯的中心介体，自1914年以来在果蝇中进行研究，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。如今，已证实Notch活性的改变是几种发育综合征（Alagille、脊椎肋骨发育不全、主动脉瓣疾病）、成人发病疾病（CADASIL、各种心脏和瓣膜畸形、肌营养不良、多发性硬化症）的基础，并以组织依赖性方式引起或促成癌症的起始、促进或进展。这些病理反映了功能丧失（例如，Alagille，CADASIL）和功能增益（例如，癌症）。由于Notch信号通路在其对蛋白酶的依赖性方面是独特的，缺乏信号调节剂，并且由于它在整个成年生活中在许多器官中重复使用，因此疾病中Notch信号传导的慢性管理之路被可用疗法的许多不利结果所掩盖。目前在抗肿瘤活动中实施的主要策略是基于g-分泌酶抑制剂或拮抗性抗体;然而，由于它们在所有器官中不加选择地抑制Notch受体，这些试剂在长期给药期间被证明是有毒的。将对这一途径的兴趣扩展到发育生物学和癌症预防之外是认识到阿尔茨海默病研究中的一个巨大障碍是难以开发能够抑制APP裂解的可靠的Notch-sparing g-分泌酶抑制剂。解决这些难题需要“跳出框框”的思维。这个跨学科但以路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名科学家组成的多元化社区，他们在每个模式生物和几乎每个器官系统中工作。参与者代表了研究Notch在发育，生物化学和遗传学中的功能的多种方法;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。重要的是，戈登会议的非正式和保密环境，以及为非正式互动提供的时间，将创造一个论坛，在这个论坛上，前沿技术、想法和发现可以自由交流，激发新的想法。最重要的是，GRC擅长整合希望进入新领域的学生，博士后和研究人员，例如对这一重要信号通路的研究。 公共卫生相关性：戈登研究会议的目标是为Notch相关生物学前沿的新研究、概念和治疗机会的传播和讨论提供一个刺激性的、国际性的和跨学科的论坛。Notch活性的改变是越来越多的发育综合征的基础或促成因素（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，肌肉萎缩症，多发性硬化症）和癌症，将对这一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，癌症生物学和治疗会议将汇集来自学术界、生物技术和制药行业的各种科学家，他们在每一种模式生物和几乎每一种器官系统中工作。

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.