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(申请人提供)：Fanconi贫血(FA)是一种罕见的遗传性疾病，以骨髓衰竭、发育异常、骨髓发育不良(MDS)、急性非淋巴细胞白血病(AML)、实体瘤和细胞对交联剂过敏为特征。Fanconi贫血的独特特征是几乎普遍发生骨髓衰竭，并且在早期发展为特定的上皮性和造血系统恶性肿瘤的相对风险很高，通常只有在老年人口中才会发现。对成年FA患者的评估显示，鳞状细胞癌(SCC)的发病率惊人且不祥，尤其是头颈部和妇科。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、环境致癌物和化疗药物对患者构成独特的风险。这些蛋白质的特定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体，在一个典型的途径中，15个已知的Fanconi贫血蛋白中的8个结合在一个复合体中，促进FANCD2的单泛素化。体外和体内证据表明，至少部分FA蛋白还通过与信号分子形成复合体来促进造血细胞的存活信号通路。干细胞移植是符合条件的骨髓衰竭患者的治疗选择。由于互补干细胞固有的选择性，这种疾病是基因治疗的理想候选者。广泛的证据表明，FA信号通路的功能障碍可以导致FA患者肿瘤细胞的体细胞变化(表观遗传和遗传)，获得性FA蛋白功能障碍也可以发生在非Fanconi患者的遗传和表观遗传中。第24届范可尼贫血研究基金会年度科学研讨会将于9月9日在科罗拉多州丹佛市举行。2012年27月30日。为期三天的会议将由受邀的主旨演讲者和大约45个单轨形式的口头摘要报告组成。大约55个额外的摘要将被选为海报演示文稿。研讨会汇集了来自世界各地的顶尖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、翻译和临床研究方面的问题。不收取注册费，部分原因是为了鼓励学生和年轻研究人员参与。这次会议为研究人员提供了一个独特的机会，让他们相互交流，开发跨学科的研究项目。本申请寻求为出席这一重要会议的演讲者和关键人员的国内旅费提供部分支持。 公共卫生相关性：一年一度的范可尼贫血研究基金科学研讨会是唯一一次专门针对范可尼贫血(FA)召开的大型科学会议。最近的研究已经确定Fanconi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方面的重要性；因此，FA科学的进展影响到的不仅仅是受这种罕见疾病影响的患者和家庭。散发性浆细胞癌、白血病、头颈癌、肺癌、卵巢癌等患者的FA基因和FA基因表达的获得性异常已有报道。