Centers for Medical Countermeasures Against Radiation

放射线医疗对策中心

• 批准号: 8306959
• 负责人: Nelson J. Chao
• 金额: $ 508.61万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-31 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306959
• 关键词: Academic Medical Centers; Acute; Address; Affect; Animals; Applied Research; Area; Arkansas; Basic Science; Biological; Biological Assay; Biomedical Engineering; Blast Cell; Blood; Blood Tests; Bone Marrow; Bone Marrow Transplantation; Brazil; Burn injury; Cells; Centers of Research Excellence; Cesium; Cessation of life; Chromosome abnormality; Cities; Clinical; Clinical Investigator; Computing Methodologies; Dedications; Development; Devices; Disasters; Discipline; Disease; Dose; Emergency Situation; Employee Strikes; Equilibrium; Etiology; Event; Explosion; Exposure to; External Beam Radiation Therapy; Failure; Femur; Fertilization; Fright; Gene Targeting; General Population; Genetic; Genomics; Goals; Government; Health; Health Physics; Health care facility; Healthcare; Hematopoietic; Hematopoietic System; Human; Immune; Immunology; Individual; Infusion procedures; Injury; Institution; Intensive Care; Ionizing radiation; Iran; Laboratories; Learning; Life; Long-Term Effects; Marketing; Marrow; Measurement; Measures; Mediating; Medical; Medical center; Methods; Minor; Modality; Modeling; Molecular Profiling; Molecular and Cellular Biology; Morbidity - disease rate; Mus; National Institute of Allergy and Infectious Disease; Normal tissue morphology; North Carolina; North Korea; Nuclear; Nuclear Power Plants; Organ; Organism; Pakistan; Pathway interactions; Patients; Persons; Pharmaceutical Chemistry; Pharmaceutical Preparations; Physics; Population; Primary Health Care; Property; Proteomics; Radiation; Radiation Injuries; Radiation Oncologist; Radiation Oncology; Radiation therapy; Radioactive; Radiobiology; Radioisotopes; Recovery; Regimen; Request for Applications; Research; Research Personnel; Research Project Grants; Role; Science; Scientist; Signal Pathway; Sorting - Cell Movement; Spleen; Stem cell transplant; Subway; Survivors; System; Test Result; Testing; Therapeutic Uses; Toxic effect; Training Programs; Training and Education; Translational Research; Transplantation Immunology; Trauma; Triage; Universities; War; Whole-Body Irradiation; Work; World War II; base; chemotherapy; dirty bomb; falls; forest; genome-wide analysis; improved; interest; internal radiation; irradiation; lectures; medical attention; novel; novel therapeutics; open source; peripheral blood; prevent; product development; programs; psychologic; research and development; response; stem cell biology; therapeutic development; trafficking; weapons; web site

DESCRIPTION (provided by applicant): Concerns about global nuclear war, less likely than in the past, have been replaced by the real potential of a terrorist strike using radiological weapons. Significant quantities of nuclear material are missing around the world and these materials could possibility enter the black market where they would be acquired by terrorists. Thus, the threat of such attacks has grown in recent years, with the increased activity of global terrorist organizations and a rise in illicit trafficking of radioactive materials. Unfortunately, very few medical products exist to counter the variety of acute and long-term toxicities that can result from nuclear or radiological attacks. Therefore, a variety of different products and medical approaches are needed to protect and treat such a population. There remains a great need to expand the medical options available to prevent or treat radiation-induced injury. We have formed a consortium termed Radiation Countermeasures Centers of Research Excellence (RadCCORE) to collectively and collaboratively increase possible agents to detect, mitigate and treat those people exposed to deterministic doses of radiation (www.radccore.org/). Leading scientists in the area of radiation biology, health physics, stem cell biology/transplantation and immunology have come together to form one of the most comprehensive, inclusive, inter-institutional, and interdisciplinary Center for Medical Countermeasures Against Radiation (CMCR). RadCCORE (www.radccore.org) is a network of academic medical centers: Duke University, University of North Carolina, Wake Forest University and University of Arkansas for Medical Sciences and will consist of seven research projects and five support cores. A major benefit of this group of investigators has been long-term dedication and strength of the individuals in the areas of normal tissue injury, radiation biology, physics, training and education. Over the past five years, it has further evolved into a highly collaborative and interactive group of investigators. This network has addressed broad areas of research, ranging from methods to precisely measure external and internal radiation doses post-exposure to the development of new therapeutic products to prevent short- and long-term toxicities. RELEVANCE: This multi-project program will develop medical treatments for people exposed to radiation. PROJECT 2: Title: - A Molecular Signature of Radiation Injury Project Leader: Chute, J PROJECT 2 DESCRIPTION (provided by applicant): In a radiological or nuclear disaster in a populated city, tens of thousands of people could be exposed to life threatening levels of ionizing radiation. Rapid triage of affected individuals will be essential for an effective health care response to such an event. Unfortunately, there is no single accurate and practical test available to determine the level of radiation exposure that a person has received. Clinical measurements are non specific and refined assays for chromosomal aberrations require several days for completion. We hypothesized that genome-wide analysis of expression changes in the peripheral blood (PB) could predict radiation status and distinguish dose levels In irradiated Individuals. Subsequently, we succeeded in developing PB signatures of radiation injury that could predict the radiation status and radiation dose level in mice with 96% accuracy. In parallel, we demonstrated that a PB signature of human radiation exposure developed from patients undergoing total body irradiation was 97% accurate at predicting the radiation status of healthy people, non-irradiated patients and irradiated patients. However, it remains to be seen whether PB signatures of total body irradiation can distinguish individuals who receive heterogeneous radiation exposure, a group that could be numerous in a mass casualty event. We also have not explored the biological significance of the pathways altered by radiation; such pathways could provide the key basis for the development of therapeutics to mitigate radiation injury. We will: 1) Determine if PB signatures of partial body irradiation can be developed as distinct from PB signatures of total body irradiation, 2) Apply high throughput computational methods to identify gene targets and pathways that are altered in hematopoietic cells in response to radiation injury and 3) Test available drugs which modulate pathways altered by radiation as candidate mitigators of radiation injury to the hematopoietic system in a validated radiation model. Our broad objective is to refine the PB signature of radiation injury to encompass those with a heterogeneous exposure and to identify signaling pathways in hematopoietic cells that are responsive to radiation injury as a means to develop pathway specific drugs as mitigators of radiation injury. RELEVANCE: In the event of a terrorist-mediated radiological or improvised nuclear detonation, tens of thousands of people may be exposed to life threatening levels of ionizing radiation. We have developed a peripheral blood test for radiation exposure based on genetic features in the blood. We propose to improve this test by testing it against partially irradiated animals and we propose to utilize the genetic information within the test results to develop drugs to treat radiation injury and minimize the damage it causes to the blood system.

描述（由申请人提供）：对全球核战争的担忧，比过去的可能性少，被使用放射武器恐怖袭击的真正潜力所取代。世界各地都缺少大量的核材料，这些材料可能进入黑市，恐怖分子将获得它们。因此，近年来，这种袭击的威胁随着全球恐怖组织的活动增加以及放射性材料的非法贩运的增加。不幸的是，很少有医疗产品与核或放射学攻击可能导致的急性和长期毒性相抵触。因此，需要各种不同的产品和医学方法来保护和治疗此类人群。仍然需要扩大可用的医疗选择，以防止或治疗辐射引起的伤害。我们形成了一个称为辐射对策研究中心（RADCCORE）的财团，以集体和协作增加可能的代理，以检测，减轻和治疗暴露于确定性辐射剂量的人（www.radccore.org/）。辐射生物学，健康物理学，干细胞生物学/移植和免疫学领域的主要科学家已经融合在一起，构成了最全面，包容性，机构间和跨学科的反辐射医学对策中心之一（CMCR）。 Radccore（www.radccore.org）是一个学术医学中心网络：杜克大学，北卡罗来纳大学，维克森林大学和阿肯色大学医学科学大学，将由七个研究项目和五个支持核心组成。这组研究人员的主要好处是在正常组织损伤，放射生物学，物理，培训和教育领域的长期奉献和力量。在过去的五年中，它进一步发展成为一个高度协作和互动的研究人员。该网络已经解决了广泛的研究领域，从方法到精确测量暴露后的外部和内部辐射剂量，再到开发新的治疗产品，以防止短期和长期毒性。 相关性：该多项目计划将为暴露于辐射的人开发医疗治疗。 项目2： 标题： - 辐射损伤的分子特征 项目负责人：Chute，J 项目2描述（由申请人提供）：在人口稠密的城市的放射学或核灾难中，数以万计的人可能会暴露于威胁生命的电离辐射水平。受影响的个体的快速分类对于对此类事件的有效医疗保健反应至关重要。不幸的是，没有一个精确且实用的测试可用于确定一个人收到的辐射暴露水平。临床测量是染色体畸变的非特异性和精制测定法需要几天才能完成。我们假设全基因组对外周血（PB）的表达变化的分析可以预测辐射状态并区分受辐射个体的剂量水平。随后，我们成功地开发了辐射损伤的PB特征，该标志可以预测具有96％精度的小鼠的辐射状态和辐射剂量水平。同时，我们证明了从接受全身照射的患者开发的人类辐射暴露的PB签名准确性为97％，以预测健康人，未射射患者和受辐照患者的辐射状态。但是，是否可以区分受到异质辐射暴露的个体，这在大规模伤亡事件中可能是很多，这群体是否可以区分那些受到异质辐射暴露的人，还有待观察。我们还没有探索辐射改变的途径的生物学意义。这样的途径可以为减轻辐射损伤的治疗剂提供关键基础。我们将：1）确定是否可以开发出部分身体照射的PB特征与全身照射的PB特征不同，2）使用高吞吐量计算方法来识别造血细胞中改变的基因靶标和途径因辐射损伤而改变的造血细胞中改变的基因靶向和3）可通过辐射射线射线射线射线射出的辐射导致辐射的辐射效果，而辐射的辐射效果会改变辐射，这 模型。我们的广泛目标是完善辐射损伤的PB特征，以包含那些患有异质暴露的人，并鉴定造血细胞中对辐射损伤有反应的信号通路，作为将特定途径药物作为放射线损伤的缓解剂的一种手段。 相关性：如果发生恐怖介导的放射学或即兴核爆炸，数以万计的人可能会暴露于威胁生命的电离辐射水平。我们已经根据血液中的遗传特征开发了用于辐射暴露的外周血测试。我们建议通过针对部分辐照的动物进行测试来改善该测试，并建议在测试结果中利用遗传信息来开发药物来治疗辐射损伤并最大程度地减少其对血液系统造成的损害。