2014 Notch Signaling in Development & Disease Gordon Research Conference/Seminar

描述(由申请者提供)：第二届Notch信号在发育、再生和疾病中的会议将于2014年7月19-25日在缅因州的贝茨学院举行，将解决学术界和工业界尚未满足的需求。这次会议的广泛和长期目标是在这个迅速扩大的领域加强跨学科的讨论和合作，并更好地解决该领域从业者遇到的无数机械、发育、组织、临床和治疗方面的挑战。Notch信号通路是后生动物短程细胞间通讯的中心媒介，自1917年以来在果蝇中进行研究，自1980年S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。最近的研究已经证实，Notch活性的变化是几种发育综合征(Alagille综合征、脊柱肋骨发育不良症、主动脉瓣疾病)、成人起病(CADASIL、各种心脏和瓣膜畸形、肌肉营养不良、多发性硬化症)的基础，并以组织依赖的方式引起或促进癌症的启动、促进或进展。这些病理既反映了功能丧失(如Alagille‘s、CADASIL)，又反映了功能获得(如癌症)。由于Notch信号通路的独特之处在于它依赖于蛋白酶，缺乏信号调节器，而且由于它在成年生活中在许多器官中反复使用，因此在疾病中长期管理Notch信号的道路被现有治疗方法的许多不良后果所掩盖。目前用于抗肿瘤活动的主要策略是基于g-分泌酶抑制剂或拮抗抗体；然而，由于它们不分青红皂白地抑制所有器官的Notch受体，长期给药的毒性仍然是一个巨大的挑战。人们对这一途径的兴趣超越了发育生物学和癌症预防，因为人们意识到，阿尔茨海默病研究中的一大障碍是开发能够抑制APP裂解的可靠的Notch省略g-分泌酶抑制剂的难度。解决这些难题需要“跳出框框”的思维。这次跨学科但以路径为重点的会议的具体目标是将来自学术界、生物技术和制药业的各种不同的科学家社区聚集在一起，这些科学家在每一个模式有机体和几乎每个器官系统上工作。参与者代表了在正常和病理情况下研究Notch功能和调节的不同方法，这将进一步促进发现和药物开发工作。预计的40位演讲者既有拥有丰富机构记忆力的老牌世界领导人，也有拥有令人兴奋的新发现的未来领导人。值得注意的是，戈登会议(GRC)的非正式和保密环境，以及为非正式互动提供的时间，将创造一个可以自由交流尖端技术、想法和发现的论坛，激发新的想法。最重要的是，GRC/GRS组合形式在整合希望进入一个新领域的学生、博士后和研究人员方面表现出色，例如研究这一重要的信号通路。

DESCRIPTION (provided by applicant): The second Notch Signaling in Development, Regeneration & Disease meeting, to be held July 19-25, 2014 at Bates College, Maine, will address an unmet need in the 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 1917 in Drosophila, in other model organisms since the 1980's, and in human health since 1991. More recent studies have established that alterations in Notch activity underlie several developmental syndromes (Alagille's Syndrome, 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's, 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, toxicity upon chronic administration remains a formidable challenge. 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 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 and regulation in normal and pathological contexts, which will further facilitate discovery and drug development efforts. The 40 projected speakers represent a blend of established world leaders with vast institutional memory and future leaders with exciting new findings to present. Significantly, the informal and confidential environment in Gordon conferences (GRCs), 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, the combined GRC/GRS format excels in integrating students, postdocs and investigators wishing to enter a new field, such as the study of this important signaling pathway.