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

基本信息

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
项目类别：
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&apos 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

项目摘要

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）：Fanconi贫血（FA）是一种罕见的遗传性疾病，其特征是骨髓衰竭，发育异常，骨髓增生的高发病率（MDS），急性非淋巴细胞性白血病（AML），实体瘤和细胞性低敏性性低下交联代理。 Fanconi贫血的独特特征是骨髓衰竭的几乎普遍发展，并且在很小的时候就出现了高度的相对风险，即通常仅在老龄化的人群中发现特定的上皮和造血恶性肿瘤。对成年FA患者的评估显示，鳞状细胞癌（SCC）的出现震撼和不祥的发生率，尤其是头部和颈部以及妇科学。此外，FA患者中体细胞的遗传不稳定意味着暴露于电离辐射，环境致癌物和化学治疗剂对患者构成独特的风险。蛋白质的特异性生化功能在很大程度上是未知的，但是许多彼此形成复合物，并且在一个规范的途径中，其中八个已知的已知fanconi贫血蛋白蛋白中有八种在复合物中结合在一起，并促进了FANCD2的单次泛素化。有体外和体内证据表明，至少某些FA蛋白还通过用信号分子形成复合物来促进造血细胞中的存活信号通路。干细胞移植是符合条件的骨髓衰竭患者的选择治疗。由于互补的干细胞的固有选择性，该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能导致FA患者引起的肿瘤细胞的躯体变化（表观遗传和遗传），并且在非癌症患者中获得的FA蛋白功能障碍也可能在遗传和表观遗传上发生。第24届年度Fanconi贫血研究基金科学研讨会将于2012年9月27日至30日在丹佛举行。为期三天的会议将由受邀的主题演讲者和大约45个口头抽象演讲组成。将选择大约55个摘要以进行海报演示。研讨会汇集了世界各地的主要研究人员和医生以及来自世界各地的年轻研究人员，讨论这种罕见疾病的基础科学，翻译和临床研究方面。不收取注册费，n部分鼓励学生和年轻调查员的参与。会议为调查人员提供了一个独特的机会，可以交叉利用和开发跨学科研究项目。该申请为演讲者和关键人员参加这次重要会议的国内旅行成本寻求部分支持。公共卫生相关性：一年一度的Fanconi贫血研究基金科学研讨会是唯一一场专门关注Fanconi贫血（FA）的大型科学会议。最近的研究确定了Fanconi贫血基因在肿瘤抑制，DNA修复，干细胞功能以及凋亡和衰老的抑制中的重要性。因此，FA科学的进步超出了受这种罕见疾病影响的患者和家庭的影响。在血浆细胞，白血病，头颈癌，肺癌和卵巢癌的零星恶性肿瘤患者中，已经报道了FA基因和FA基因表达的异常。