Center for Translational Viral Oncology (CTVO)

摘要：Cobre的主要目标是加强路易斯安那州的生物医学研究基础设施 通过培训有前途的初级调查人员(PJI)，他们能够开发针对主要问题的独立研究 我们地区的健康问题。病毒相关癌症仍然是我国发病率和死亡率的主要原因。 而且对非洲裔美国人的影响不成比例。其中包括与HPV相关的宫颈， 肛门生殖器癌、头颈部癌、KSHV相关卡波西肉瘤和原发渗出性淋巴瘤， 丙型肝炎病毒和乙肝病毒相关的肝癌和其他，所有这些都在我们地区异常地高度流行。 这些疾病的增加可能在一定程度上是由于中国感染艾滋病毒的患者数量很大 区域。此外，我们的数据还表明，细胞与一种以上病毒的混合感染会促进或 与恶变有关。因此，了解特定的病毒和病毒是如何 感染促进恶性肿瘤的发展对于识别和实施新的 预防、诊断和治疗战略。因此，培训一支有能力的新的调查人员队伍 在病毒肿瘤学领域进行新的研究对我们州来说是至关重要的。这将会实现的 通过开发一个利用现有资源的翻译病毒肿瘤学中心(CTVO) 培训新的研究人员，开发新的实验室基础设施，并支持旨在 在我们独特的人群中研究这些疾病。CTVO将支持科学、指导和 通过提供(I)由美国国立卫生研究院资助的和 致力于指导PJI开发尖端技术的国际公认的调查人员 研究，确保他们的成功培训，并支持他们作为独立研究人员的发展； (Ii)来自高危患者群体的独特临床材料--PJI将优先获得独特的 (而且还在增加)一组来自HIV+和HIV病毒相关患者的临床注释的生物样本 在大学医学中心收集的癌症-新奥尔良(III)完善的管理和 尖端科学基础设施，包括整合的癌症和艾滋病毒临床试验计划，以翻译 这些项目的发现，先进的核心研究实验室，以及一个新的扩展和独特的 生物库，艾滋病毒/临床肿瘤生物库(HCTB)的核心。最初，这个科布雷带来了四个项目 通过PJIS研究致癌病毒如HPV、KSHV和EBV的作用以及增加的病毒 对人类致癌感兴趣，如人巨细胞病毒、人内源性逆转录病毒 序列(HERV)和人类嗜神经性多瘤病毒JC(JCV)。这些癌症更常发生在 免疫缺陷(包括艾滋病毒感染)的背景，并不成比例地影响非裔美国人 路易斯安那州的病人。拟议工作的实施将以下列具体目标为指导：1) 建立跨学科的调查团队和实验室核心基础设施，以支持PJI领导的 病毒-宿主相互作用及其在癌症发病机制中作用的研究项目；2)开发一种 行政基础设施，以指导和促进PJI的独立事业；以及3)利用 NIH资助的机构中心和参与机构的方案，以促进 临床和转化性研究基础设施中的PJI。该计划的完成将提供 该地区有更强的能力来解决这些和其他可能出现的与病毒有关的健康问题 在未来。

Abstract: The primary goal of this COBRE is to strengthen the biomedical research infrastructure in Louisiana by training Promising Junior Investigators (PJIs) who can develop independent research addressing a major health problem in our region. Virus-associated cancers remain a major cause of morbidity and mortality in our region and disproportionately affect the African American population. These include HPV- associated cervical, anogenital, and head and neck cancers, KSHV-associated Kaposi sarcoma and primary effusion lymphoma, HCV- and HBV-associated liver cancers and others, all which are unusually highly prevalent in our area. Increases in these diseases may be explained, in part, by the large number of HIV-infected patients in the region. In addition, our data also indicate that co-infection of cells with more than one virus promotes or associates with malignant transformation. Therefore, understanding how particular viruses and viral co- infections promote the development of malignancies is essential to identifying and implementing new preventative, diagnostic and treatment strategies. It follows that training a new cadre of investigators capable of conducting novel research in the field of viral oncology is essential for our state. This will be accomplished by developing a Center for Translational Viral Oncology (CTVO) that leverages existing resources in order to train new investigators, develops novel laboratory infrastructure, and supports research projects designed to study these diseases in our unique populations. The CTVO will support the scientific, mentoring and administrative needs of the PJIs by providing (i) experienced mentoring teams composed of NIH-funded and internationally recognized investigators who are committed to guiding PJIs in developing cutting edge research, ensuring their successful training, and supporting their development as independent researchers; (ii) unique clinical material from high risk patient populations – PJIs will have preferential access to a unique (and increasing) set of clinically annotated biospecimens from HIV+ and HIV- patients with virus-associated cancers collected at the University Medical Center – New Orleans (iii) well-established administrative and cutting edge scientific infrastructure including integrated cancer and HIV clinical trials programs to translate the findings of these projects, advanced core research laboratories, and a new expanded and unique biorepository, the HIV/Clinical Tumor Biorepository (HCTB) Core. Initially, this COBRE brings four projects led by PJIs to study the role of oncogenic viruses such as HPV, KSHV and EBV, as well as, viruses of increasing interest in human carcinogenesis such as human cytomegalovirus (HCMV), human endogenous retrovirus sequences (HERVs), and human neurotropic Polyomavirus JC (JCV). These cancers arise more commonly in the setting of immune deficiencies (including HIV infection), and disproportionately affect African American patients in Louisiana. Implementation of the proposed work will be directed by the following Specific Aims: 1) to establish interdisciplinary teams of investigators and laboratory core infrastructure to support PJI-led research projects on virus-host interactions and their role in pathogenesis of cancer; 2) to develop an administrative infrastructure to mentor and promote the independent career of the PJIs; and 3) to leverage institutional NIH-funded Centers and Programs at the participating institutions to facilitate the integration of PJIs within the clinical and translational research infrastructure. The completion of this program will provide this region with enhanced capabilities to address these and other virus related health problems that may arise in the future.