The role of indolamine2,3-dioxygenase in the host response/pathogenesis of Venezu

吲哚胺2,3-双加氧酶在Venezu宿主反应/发病机制中的作用

• 批准号: 8568455
• 负责人: Robert Seymour
• 金额: $ 17.41万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8568455
• 关键词: Academy; Aerosols; Alphavirus; Amino Acids; Animals; Antibodies; Archives; Area; Astrocytes; Autopsy; Award; Biological; Biological Markers; Brain; Cause of Death; Cells; Clinical; Culicidae; Development; Dioxygenases; Discipline; Disease; Disease Outcome; Eastern Equine Encephalitis Virus; Eastern Equine Encephalomyelitis; Educational process of instructing; Encephalitis; Enhancers; Environment; Enzymes; Epidemic; Evaluation; Faculty; Family; Feedback; Funding; Goals; HIV Encephalopathy; High Pressure Liquid Chromatography; Histologic; Human; Immune response; Immune system; Immunohistochemistry; Immunology; In Vitro; Infection; Inflammation; International; Journals; Knockout Mice; Lead; Long-Term Effects; Macaca; Macaca fascicularis; Measurement; Measures; Medical Students; Mentors; Microglia; Military Personnel; Monitor; Morbidity - disease rate; Mus; Neuraxis; Neuropathogenesis; O' nyong-nyong virus; Outcome; Pathogenesis; Pathology; Pathway interactions; Pattern; Persons; Phenotype; Physicians; Play; Positioning Attribute; Process; Production; Public Health; RNA Viruses; Recruitment Activity; Research; Research Activity; Research Personnel; Research Project Grants; Research Proposals; Role; Route; Scientist; Serum; Services; Source; Spectrophotometry; Supportive care; T-Lymphocyte; Testing; Therapeutic; Time; Tissue Sample; Togaviridae; Tryptophan; Tryptophan 2,3 Dioxygenase; USSR; United States; Venezuelan Equine Encephalitis Virus; Venezuelan Equine Encephalomyelitis; Viral; Viral Antigens; Virulent; Virus; Virus Diseases; War; Wild Type Mouse; Work; Writing; aerosolized; base; chikungunya; effective therapy; enzootic; epizootic; graduate student; immunoregulation; improved; in vivo Model; indolamine; indoleamine; inhibitor/antagonist; interest; macrophage; meetings; member; monocyte; mortality; programs; public health relevance; response; skills; transmission process; vaccine candidate; vaccine development; weapons

DESCRIPTION (provided by applicant): The goal of this research proposal is to determine the role of IDO (indolamine 2,3-dioxygenase) in the pathogenesis/host response to infection by Venezuelan equine encephalitis (VEEV) and eastern equine encephalitis (EEEV) viruses. These viruses, particularly VEEV, were developed as biological weapons by the United States Military and former USSR during the cold war and are potential bioterrorist threats due to their ease of transmission and infectivity by the aerosol route. The neuropathogenesis of these viruses and the host response of the central nervous system are still not completely understood. These viruses can cause death and long term sequelae in those that survive. Eastern equine encephalitis is partially virulent with a mortality of more than 50% in those with symptomatic disease. Through this study we hope to discover new ways in which the host's central nervous system reacts to infection from these viruses. If we can better understand the role IDO plays in this process we may be able to develop therapeutics to alleviate disease. Currently the only treatment available for these viruses is symptomatic and supportive therapy. The potential for these viruses to be used as bioweapons and their easy aerosol transmission makes the search for directed therapies of great importance. Dr. Seymour has the necessary skills to carry this project forward while at the same time acquiring new skills and improving his current skills. He will spend 9-person months on this project. The remainder of his time will be devoted to other research projects including work with vaccine candidates against chikungunya, EEEV, VEEV. He will also continue his work on elucidating the role of T-cells in chikungunya infection and his work concerning the pathogenesis of O'nyong-nyong virus. His other activities will include functioning as an attending of the autopsy service for 1 month per year and he will be involved in teaching medical and graduate students. He will have the opportunity to interact with other faculty members during seminars, journal clubs and colloquiums. He will also participate in the department of pathology "pre-proposal presentation" program for faculty members, which allows them to present their ideas before other faculty members in the department to garner feedback and advice in making their proposal stronger. UTMB recently developed the Academy of Research Mentors and this academy will provide Dr. Seymour with an independent mentor with interests complementary to Dr. Weaver's. He will meet regularly with Dr. Weaver and Dr. Aronson to discuss his progress and ongoing research activities. He will be expected to present his work at the weekly pathology seminar. In addition, he will present his work at least two national or international meetings per year. He will participate in seminars and classes which will focus on the responsible conduct of research, grant writing and among others. During his final two years on this award he will begin to apply for his own independent funding. His immediate goal is to pursue a tenor track position and develop his skill set which will allow him to reach hi long term goal of becoming a successful independent physician-scientist in arboviral immunology and arboviral vaccine development/treatment. The rich research environment at UTMB with numerous successful investigators in arbovirology and other disciplines give him a unique and supportive environment to reach his goals.

描述（由申请人提供）：该研究建议的目的是确定iDo（吲哚胺2,3-二加氧酶）在委内瑞拉北马脑炎（VEEV）和东部马脑炎（EEEV）病毒对感染的发病机理/宿主反应中的作用。这些病毒，尤其是VEEV，是由美国军方和前苏联在冷战期间作为生物武器开发的，由于气溶胶路线的传播和感染性易于传播和感染性，这是潜在的生物恐怖主义威胁。这些病毒的神经病发生和中枢神经系统的宿主反应仍未完全了解。这些病毒可能在生存的病毒中引起死亡和长期后遗症。东马脑炎部分有毒，有症状性疾病患者的死亡率超过50％。通过这项研究，我们希望发现宿主的中枢神经系统对这些病毒感染的反应的新方法。如果我们能够更好地理解IDO在此过程中的作用，那么我们可能能够发展以减轻疾病的治疗剂。目前，这些病毒可用的唯一治疗方法是症状和支持疗法。这些病毒被用作生物武器及其简单的气溶胶传播的潜力使得寻找非常重要的定向疗法。 Seymour博士具有必要的技能，可以使该项目继续前进，同时又获得了新技能并提高了他当前的技能。他将在这个项目上花9个月。他的剩余时间将专门用于其他研究项目，包括与Chikungunya，EEEV，Veev的疫苗候选人合作。他还将继续他的工作，以阐明T细胞在Chikungunya感染中的作用以及关于O'Nyong-Nyong病毒发病机理的工作。他的其他活动将包括作为每年1个月的尸检服务的工作，他将参与教授医学和研究生。他将有机会在研讨会，期刊俱乐部和座谈会上与其他教职员工互动。他还将为教职员工参加病理学系“预言介绍”计划，该计划使他们能够在该系的其他教职员工面前介绍自己的想法，以吸引反馈和建议，以提高他们的建议。 UTMB最近开发了研究学院的导师学院，该学院将为Seymour博士提供一位独立的导师，对Weaver博士的兴趣进行了兴趣。他将定期与Weaver博士和Aronson博士会面，讨论他的进步和正在进行的研究活动。期望他在每周的病理研讨会上介绍他的作品。此外，他将每年至少举行两次全国或国际会议。他将参加研讨会和课程 专注于负责任的研究，赠款写作等。在获得该奖项的最后两年中，他将开始申请自己的独立资金。他的近期目标是追求男高音轨道地位并发展自己的技能，这将使他能够达到成功的长期目标，即成为成功的独立医师 - 科学家在Arboviral免疫学和arboviral疫苗开发/治疗方面。 UTMB的丰富研究环境与众多成功的Arboviorology和其他学科的研究人员为他提供了实现目标的独特而支持的环境。