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.
|Effective start/end date||9/7/12 → 8/31/13|
- National Institutes of Health: $10,001.00
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