24th Annual Fanconi Anemia Research Fund Scientific Symposium

第24届年度范可尼贫血研究基金科学研讨会

• 批准号: 8398885
• 负责人: Grover Carlton Bagby
• 金额: $ 1万
• 依托单位: FANCONI ANEMIA RESEARCH FUND, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-07 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8398885
• 关键词: Acute; Adult Fanconi Anemia; Affect; Age; Aging; Apoptosis; Basic Science; Biochemical; Candidate Disease Gene; Cell physiology; Cells; Charge; Clinical Management; Clinical Research; Complement; Complex; DNA Repair; Development; Disease; Dysmyelopoietic Syndromes; Employee Strikes; Environmental Carcinogens; Epigenetic Process; Epithelial; Evaluation; Exposure to; Family; Fanconi anemia protein; Fanconi' s Anemia; Fees; Functional disorder; Funding; Gene Expression; Genes; Genetic; Genetic Heterogeneity; Genotype; Head and Neck Cancer; Head and neck structure; Hematopoietic; Hematopoietic Neoplasms; Hereditary Disease; Human Papillomavirus; Human Resources; Hypersensitivity; In Vitro; Incidence; Individual; Interdisciplinary Study; Ionizing radiation; Knowledge; Laboratory Diagnosis; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Monoubiquitination; Myeloid Leukemia; Oral; Pancytopenia; Pathway interactions; Patients; Phenotype; Physicians; Plasmacytic Leukemia; Population; Protein Binding; Rare Diseases; Relative Risks; Reporting; Research; Research Personnel; Research Project Grants; Risk; Role; Science; Signal Pathway; Signaling Molecule; Solid Neoplasm; Somatic Cell; Squamous cell carcinoma; Stem cell transplant; Stem cells; Students; Transplantation; Travel; Tumor Suppression; Update; abstracting; chemotherapeutic agent; clinical Diagnosis; cost; crosslink; gene therapy; in vivo; induced pluripotent stem cell; meetings; neoplastic cell; posters; protein complex; protein function; senescence; small molecule; symposium

DESCRIPTION (provided by applicant): Fanconi anemia (FA) is a rare hereditary disease characterized by bone marrow failure, developmental anomalies, high incidence of myelodysplasia (MDS), acute non-lymphocytic leukemia (AML), solid tumors, and cellular hypersensitivity to cross-linking agents. Unique features of Fanconi anemia are the nearly universal development of bone marrow failure and a high relative risk of developing, at an early age, specific epithelial and hematopoietic malignancies usually found only in aging populations. Evaluation of adult FA patients reveals a striking and ominous incidence of squamous cell carcinomas (SCC), especially of the head and neck and gynecological tract. Moreover, the genetic instability of the somatic cells in the FA patient means that exposure to ionizing radiation, environmental carcinogens and chemotherapeutic agents pose unique risks to the patient. The specific biochemical functions of the proteins is largely unknown, but many form complexes with each other and in one canonical pathway, eight of the fifteen known Fanconi anemia proteins bind together in a complex and facilitate the monoubiquitination of FANCD2. There is in vitro and in vivo evidence suggesting that at least some of the FA proteins also promote survival signaling pathways in hematopoietic cells by forming complexes with signaling molecules. Stem cell transplantation is the treatment of choice for eligible patients with bone marrow failure. The disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells. Broad evidence is being developed that dysfunction of the FA signaling pathways can result in somatic changes (epigenetic and genetic) in neoplastic cells arising in FA patients and that acquired FA protein dysfunction can also occur genetically and epigenetically in non-Fanconi patients. The 24th Annual Fanconi Anemia Research Fund Scientific Symposium will be held in Denver, CO, Sept. 27-30, 2012. The three-day conference will be comprised of invited keynote speakers and approximately 45 oral abstract presentations in a single-track format. Approximately 55 additional abstracts will be selected for poster presentations. The Symposium brings together leading researchers and physicians as well as young investigators from around the world to discuss basic science, translational, and clinical research aspects of this rare disease. No registration fee is charged, n part to encourage participation of students and young investigators. The meeting provides a unique opportunity for investigators to cross-fertilize and develop interdisciplinary research projects. This application seeks partial support for domestic travel costs for speakers and key personnel to attend this important conference. PUBLIC HEALTH RELEVANCE: The annual Fanconi Anemia Research Fund Scientific Symposium is the only major scientific conference convened to focus exclusively on Fanconi anemia (FA). Recent research has established the importance of Fanconi anemia genes in tumor suppression, DNA repair, stem cell function, and suppression of apoptosis and senescence; thus, advances made in FA science have an impact beyond patients and families affected by this rare disease. Acquired abnormalities of FA genes and FA gene expression have been reported in patients with sporadic malignancies of plasma cells, leukemia, head and neck cancer, lung cancer, and ovarian cancer.

描述（由申请人提供）：范可尼贫血（FA）是一种罕见的遗传性疾病，其特征为骨髓衰竭、发育异常、骨髓增生异常（MDS）、急性非淋巴细胞白血病（AML）、实体瘤和对交联剂的细胞超敏反应的高发生率。范可尼贫血的独特特征是几乎普遍发生骨髓衰竭，并且在早期发生通常仅在老年人群中发现的特定上皮和造血恶性肿瘤的相对风险较高。对成年FA患者的评估揭示了鳞状细胞癌（SCC）的惊人和不祥的发病率，特别是头颈部和妇科道。此外，FA患者体细胞的遗传不稳定性意味着暴露于电离辐射、环境致癌物和化疗剂对患者构成独特的风险。这些蛋白质的具体生化功能在很大程度上是未知的，但许多蛋白质彼此形成复合物，在一个典型的途径中，十五种已知的范可尼贫血蛋白中的八种以复合物的形式结合在一起，并促进FANCD 2的单泛素化。体外和体内证据表明，至少一些FA蛋白还通过与信号分子形成复合物来促进造血细胞中的生存信号通路。干细胞移植是符合条件的骨髓衰竭患者的治疗选择。这种疾病是一个理想的候选基因治疗，因为固有的选择性补充干细胞。 正在开发的广泛证据表明，FA信号通路的功能障碍可导致FA患者中产生的肿瘤细胞的体细胞变化（表观遗传和遗传），并且获得性FA蛋白功能障碍也可在非Fanconi患者中发生遗传和表观遗传。 第24届范科尼贫血研究基金科学研讨会将于9月9日在科罗拉多州丹佛市举行。2012年27-30日。为期三天的会议将由特邀主旨发言人和大约45个单轨格式的口头摘要介绍组成。将另外选择大约55篇摘要用于海报展示。研讨会汇集了来自世界各地的领先研究人员和医生以及年轻的研究人员，讨论这种罕见疾病的基础科学，转化和临床研究方面。不收取注册费，部分是为了鼓励学生和年轻研究人员的参与。会议为研究人员提供了一个独特的机会，以交叉施肥和开发跨学科的研究项目。该申请寻求对发言者和主要人员参加这一重要会议的国内差旅费的部分支持。 公共卫生关系：一年一度的范可尼贫血研究基金科学研讨会是唯一一个专门关注范可尼贫血（FA）的大型科学会议。最近的研究已经确定了范可尼贫血基因在肿瘤抑制，DNA修复，干细胞功能以及抑制细胞凋亡和衰老中的重要性;因此，FA科学的进步对这种罕见疾病的患者和家庭产生了影响。在散发性恶性肿瘤如浆细胞癌、白血病、头颈癌、肺癌和卵巢癌患者中已报道了获得性FA基因和FA基因表达异常。