26th Annual Fanconi Anemia Research Fund Scientific Symposium

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(BMF)、发育异常、细胞对交联剂的超敏反应以及包括骨髓发育不良、急性非淋巴细胞白血病和实体瘤在内的高发病率的恶性肿瘤。FA的独特特征是BMF几乎普遍发生，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，通常只有在老年人群中才能发现。对成年FA患者的评估显示，鳞状细胞癌的发病率很高，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在电离辐射中；环境致癌物质和化疗药物对患者构成独特的风险。FA蛋白质的具体生化功能在很大程度上尚不清楚，但许多蛋白质相互形成复合体，在一条典型的“途径”中，16种已知FA蛋白质中的8种结合在一起，形成一个复合体，促进FANCD2的单泛素化。体外和体内证据表明，至少部分FA蛋白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。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)，并且FA蛋白功能障碍 在非Fanconi患者中可通过多种机制获得。FA的多种病理改变的治疗选择仍然有限。造血干细胞移植仍然是符合条件的骨髓衰竭患者的治疗选择。然而，由于补体干细胞固有的选择性，这种疾病是基因治疗的理想候选者。需要新的治疗方案来治疗其他FA相关的病理，包括鳞癌，特别是当患者不能耐受传统的放射和化疗方法来治疗恶性肿瘤时。第26届范可尼贫血研究基金会年度科学研讨会将于2014年9月18日至21日在马里兰州贝塞斯达举行。预计大约200名研究人员和临床医生将参加为期三天的会议，包括受邀的主旨和/或特别会议演讲者和大约45个单轨形式的口头摘要演示，其间穿插着一到两个旨在提高互动性的小组演示。大约60个额外的摘要可能被选为海报演示文稿。研讨会汇集了国际领先的研究人员和内科医生以及年轻的研究人员，讨论这种罕见疾病的基础科学、翻译和临床方面的问题。延长的海报会议招待会和现场用餐促进了持续的讨论。这次会议为调查人员提供了一次独特的机会，可以相互促进和发展跨学科研究项目，随后收到的供基金审议的研究提案就证明了这一点。不收取注册费。对口头摘要演讲者、主旨发言人和特别会议参与者的旅费予以报销。如有要求，海报演示者可获得有限的旅行支持，否则他们将无法出席。此应用程序寻求支持演讲者、关键人员和年轻研究人员参加这一重要会议的旅费。

DESCRIPTION (provided by applicant): Fanconi anemia (FA) is a rare hereditary disease characterized by bone marrow failure (BMF), developmental anomalies, cellular hypersensitivity to cross-linking agents and a high incidence of malignancy including myelodysplasia, acute non-lymphocytic leukemia, and solid tumors. Unique features of FA are the nearly universal development of BMF 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 incidence of squamous cell carcinomas, 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 FA proteins are largely unknown, but many form complexes with each other and in one canonical "pathway," 8 of the 16 known FA proteins bind together in a complex that facilitates the monoubiquitination of FANCD2. In vitro and in vivo evidence suggests that at least some of the FA proteins promote survival signaling pathways in hematopoietic cells by forming complexes with signaling molecules. 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 FA protein dysfunction can be acquired by several mechanisms in non-Fanconi patients. Treatment options for the multiple pathologies of FA remain limited. Hematopoietic stem cell transplantation remains the treatment of choice for eligible patients with bone marrow failure. However, this disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells. Novel therapeutic options are needed to treat the other FA-related pathologies, including squamous cell carcinomas, particularly as the patients cannot tolerate conventional radiation and chemotherapeutic approaches to malignancy. The 26th Annual Fanconi Anemia Research Fund Scientific Symposium will be held in Bethesda, Maryland, September 18-21, 2014. Approximately 200 researchers and clinicians are expected to participate in the three-day conference comprised of invited keynote and/or special session presenters and approximately 45 oral abstract presentations in a single-track format, interspersed with one or two panel presentations designed for greater interactivity. Approximately 60 additional abstracts may be selected for poster presentations. The Symposium brings together an international assemblage of leading researchers and physicians as well as young investigators to discuss basic science, translational, and clinical aspects of this rare disease. Extended poster session receptions and on-site meals foster ongoing discussion. The meeting provides a unique opportunity for investigators to cross-fertilize and develop interdisciplinary research projects, as evidenced by subsequent research proposals received for the Fund's consideration. No registration fee is charged. Travel expenses are reimbursed for oral abstract presenters, key-note speakers and special session participants. Limited travel support is available upon request for poster presenters who would otherwise be unable to attend. This application seeks support for travel costs for speakers, key personnel, and young investigators to attend this important conference.