13th International Workshop on Ataxia-Telangiectasia and ATM

第13届共济失调-毛细血管扩张与ATM国际研讨会

• 批准号: 7483575
• 负责人: RICHARD A GATTI
• 金额: $ 2.05万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7483575
• 关键词: ATM gene; ATM wt Allele; Affect; Alleles; Animal Model; Area; Aspiration Pneumonia; Ataxia Telangiectasia; Breast; Cell Cycle Checkpoint; Cell Line; Cells; Cerebellar Ataxia; Child; Chromatin; Clinical; Clinical Trials; DNA Damage; DNA Double Strand Break; Deglutition; Development; Disease; Drug Delivery Systems; Educational workshop; Family; Future; Gait; General Population; Genomic Instability; Goals; Hereditary Disease; Heterozygote; Human; Immunologic Deficiency Syndromes; Incidence; Infection; International; Ionizing radiation; Lead; Life; Live Birth; Lymphoma; Malignant Neoplasms; Molecular; Mutation; Nerve Degeneration; Nervous system structure; Neurodegenerative Disorders; Neurologic; Patients; Pharmaceutical Preparations; Phosphatidylinositols; Phosphotransferases; Predisposition; Protein-Serine-Threonine Kinases; Proteins; Public Health; Radiation; Radiation Tolerance; Radiation, Other; Research; Research Personnel; Risk; Role; Study models; Symptoms; Teenagers; Virus Diseases; Wheelchairs; Work; ataxia telangiectasia mutated protein; base; cancer epidemiology; design; leukemia; malignant breast neoplasm; member; neurodevelopment; response

DESCRIPTION (provided by applicant): Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder that affects approximately 1 in 40,000 live births worldwide. It is characterized by a progressive cerebellar ataxia, telangiectasia, immunodeficiency, genomic instability, radiation sensitivity, and a markedly increased incidence of cancer, usually lymphoma or leukemia. Symptoms of A-T are typically manifested during the first few years of life with a wobbly gait. Loss of neuromuscular control is relentless and, by their teens, the children are usually confined to a wheel chair. They also have neurological swallowing problems which can lead to aspiration pneumonia and sinupulmonary infections. 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, which is a member of the phosphatidyl inositol 3 kinase family of serine/threonine protein kinases. The major role of ATM appears to be in DNA damage recognition, especially of double strand DNA breaks. 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. Understanding the function of ATM is of considerable importance to understanding the role of ATM in neural development and neurodegeneration, the molecular basis for increased cancer predisposition in A-T patients and ATM heterozygotes, and the molecular mechanisms that control how cells respond to radiation damage and radiomimetic chemotherapeutic drugs. A-T has also become a model for the study of mutation-targeted drugs for treating genetic diseases since hundreds of patient-derived cell lines are available, with identified mutations. Objectives of the 13th International Workshop on Ataxia-Telangiectasia and ATM meeting: The objectives of the meeting are to bring together an international group of basic and clinical researchers working on various aspects of A-T and related neurodegenerative diseases, as well as on the role of ATM in cancer, the DNA damage response, and in viral infections. Our goal is to stimulate research that will lead to better understanding and treatment of 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 and genomic instability in the activation of ATM, the role of ATM in the developing nervous system and in neurodegeneration, animal models of A-T, ATM mutations in breast and other human cancers, the epidemiology of ATM mutations, and the development of new treatments for A-T and the design of future clinical trials for A-T patients worldwide. We also hope to encourage new young investigators to both clinical and basic A-T/ATM research. PUBLIC HEALTH RELEVANCE: 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 and genomic instability in the activation of ATM, the role of ATM in the developing nervous system and in neurodegeneration, animal models of A-T, ATM mutations in breast and other human cancers, the epidemiology of ATM mutations, and the development of new treatments for A-T and the design of future clinical trials for A-T patients worldwide. We also hope to encourage new young investigators to both clinical and basic A-T/ATM research.

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，影响全球大约四万分之一的活产儿。其特征是进行性小脑共济失调、毛细血管扩张、免疫缺陷、基因组不稳定、辐射敏感性以及癌症（通常是淋巴瘤或白血病）发病率显着增加。 A-T 的症状通常在生命的最初几年表现为步态摇摇晃晃。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。他们还存在神经性吞咽问题，可能导致吸入性肺炎和鼻窦肺部感染。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/苏氨酸蛋白激酶的磷脂酰肌醇 3 激酶家族的成员。 ATM 的主要作用似乎是在 DNA 损伤识别中，尤其是双链 DNA 断裂。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。了解ATM的功能对于理解ATM在神经发育和神经变性中的作用、A-T患者和ATM杂合子中癌症易感性增加的分子基础、以及控制细胞如何响应辐射损伤和拟放射化疗药物的分子机制具有相当重要的意义。 A-T 也已成为研究用于治疗遗传疾病的突变靶向药物的模型，因为可以使用数百种源自患者的细胞系，并已识别出突变。第十三届共济失调-毛细血管扩张和 ATM 会议国际研讨会的目标：会议的目标是汇集国际基础和临床研究人员小组，研究 A-T 和相关神经退行性疾病的各个方面，以及 ATM 在癌症、DNA 损伤反应和病毒感染中的作用。我们的目标是促进研究，以更好地理解和治疗 A-T。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、染色质和基因组不稳定性在ATM激活中的重要性、ATM在神经系统发育和神经变性中的作用、A-T动物模型、乳腺癌和其他人类癌症中的ATM突变、ATM突变的流行病学、A-T新疗法的开发以及针对全球A-T患者的未来临床试验的设计。我们还希望鼓励新的年轻研究人员进行临床和基础 A-T/ATM 研究。 公共健康相关性：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、染色质和基因组不稳定性在 ATM 激活中的重要性、ATM 在神经系统发育和神经变性中的作用、A-T 动物模型、乳腺癌和其他人类癌症中的 ATM 突变、ATM 突变的流行病学、A-T 新疗法的开发以及 A-T 未来临床试验的设计 全世界的患者。我们还希望鼓励新的年轻研究人员进行临床和基础 A-T/ATM 研究。