12th International Workshop on Ataxia-Telangiectasia and ATM

第十二届共济失调毛细血管扩张与 ATM 国际研讨会

• 批准号: 7163680
• 负责人: RICHARD A GATTI
• 金额: $ 1万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163680
• 关键词: ataxia telangiectasia; molecular pathology; workshop

DESCRIPTION (provided by applicant): Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder that affects approximately 1 in 40,000 to 1 in 100,000 live births. A-T is characterized by progressive cerebellar ataxia, telangiectasia, immunodeficiency, chromosomal instability, radiation sensitivity and increased incidence of lymphoid malignancies. Symptoms of A-T usually manifest in the first few years of life when children exhibit wobbly gait. Loss of neuromuscular control is relentless and, by their teens, children are usually confined to a wheel chair. A-T patients usually succumb to infection and/or lymphoma in the second decade of life. In addition, it has been estimated that up to 1% of the general population carries mutations in one allele of the ATM (ataxia-telangiectasia mutated) gene and ATM heterozygotes have an increased risk of developing breast cancer. The ATM gene encodes a large (369 kDa) protein, ATM, that is a member of the phosphatidyl inositol 3 kinase family of serine threonine protein kinases (the PIKKs). Cells that lack ATM are highly sensitive to ionizing radiation (IR) and are defective in the activation of multiple cell cycle checkpoints in response to IR and other DNA damaging agents. Since the discovery of the gene in 1995, it has become apparent that ATM plays a critical role in regulating the cellular response to IR and other DNA damaging agents. Understanding the function of ATM is of considerable importance to understanding the etiology of the disease, the molecular basis for increased cancer predisposition in A-T patients and ATM heterozygotes, and the molecular mechanisms that control how cells respond to radiotherapy and many chemotherapeutic drugs. In this application, funds are requested for partial support towards the 12th International Workshop on Ataxia-Telangiectasia and ATM, which will be held at the Banff Centre, Banff, Alberta, Canada, September 8th to 12th 2006. Objectives of the meeting: The objectives of the meeting are to bring together basic and clinical researchers working on various aspects of the clinical features of A-T, the role of ATM in the DNA damage response, and the role of ATM in the nervous system, in an informal but stimulating scientific atmosphere which will promote scientific interactions, discussions and research collaborations into understanding the functions of ATM and the biological basis of A-T. Our goal is to stimulate research that will lead to better understanding of and treatments for A-T. Specific areas of focus of the meeting will include the role of ATM and related proteins in the DNA damage response, the importance of chromatin in the activation of ATM, the role of ATM in the nervous system, mechanisms of neurodegeneration, the role of other DNA damage proteins in neuropathies, animal models of A-T, ATM in breast and other human cancers, epidemiology of ATM mutations, towards the development of new treatments for A-T, and an update on clinical trials for A-T.

描述（由申请人提供）：共济失调毛细血管扩张症 (A-T) 是一种罕见的常染色体隐性遗传疾病，影响大约四万分之一到十万分之一的活产儿。 A-T 的特点是进行性小脑共济失调、毛细血管扩张、免疫缺陷、染色体不稳定、辐射敏感性和淋巴恶性肿瘤发病率增加。 A-T 的症状通常在生命的最初几年表现出来，此时儿童表现出步态不稳。 神经肌肉控制的丧失是无情的，到了十几岁的时候，孩子们通常只能坐在轮椅上。 A-T 患者通常在生命的第二个十年死于感染和/或淋巴瘤。 此外，据估计，高达 1% 的普通人群携带 ATM（共济失调毛细血管扩张突变）基因的一个等位基因突变，ATM 杂合子患乳腺癌的风险增加。 ATM 基因编码一个大的 (369 kDa) 蛋白 ATM，它是丝氨酸苏氨酸蛋白激酶 (PIKK) 的磷脂酰肌醇 3 激酶家族的成员。 缺乏 ATM 的细胞对电离辐射 (IR) 高度敏感，并且在响应 IR 和其他 DNA 损伤剂而激活多个细胞周期检查点方面存在缺陷。 自 1995 年发现该基因以来，ATM 在调节细胞对 IR 和其他 DNA 损伤剂的反应中发挥着关键作用，这一点已变得显而易见。 了解 ATM 的功能对于了解该疾病的病因、A-T 患者和 ATM 杂合子癌症易感性增加的分子基础，以及控制细胞对放疗和许多化疗药物反应的分子机制非常重要。 在此申请中，请求资金为第 12 届共济失调毛细血管扩张和 ATM 国际研讨会提供部分支持，该研讨会将于 2006 年 9 月 8 日至 12 日在加拿大艾伯塔省班夫班夫中心举行。 会议目标： 目标会议的目的是汇集基础和临床研究人员，研究 A-T 临床特征、ATM 在 DNA 损伤反应中的作用以及 ATM 在神经系统中的作用等各个方面。系统，在非正式但刺激的科学氛围中，将促进科学互动、讨论和研究合作，以了解 ATM 的功能和 A-T 的生物学基础。 我们的目标是促进研究，从而更好地了解 A-T 并对其进行治疗。 会议的具体重点领域将包括ATM和相关蛋白在DNA损伤反应中的作用、染色质在ATM激活中的重要性、ATM在神经系统中的作用、神经退行性变的机制、其他DNA的作用神经病中的损伤蛋白、A-T 动物模型、乳腺癌和其他人类癌症中的 ATM、ATM 突变的流行病学、A-T 新疗法的开发以及 A-T 临床试验的最新情况。