Comprehensive NeuroAIDS Center

 描述(申请人提供)：神经系统并发症和相关疾病，包括艾滋病毒-1相关的神经认知障碍或手，即使在接受抗逆转录病毒治疗后，仍是艾滋病毒-1感染最具破坏性的临床表现之一。因此，现在人们普遍认识到，需要一种新的战略来根除艾滋病及其相关的共病，因为目前的抗逆转录病毒疗法未能从受感染的宿主中消除艾滋病毒-1。在这里，我们寻求支持，以继续运营急需的综合神经艾滋病核心中心(CNAC)，该中心于2011年在坦普尔大学医学院与费城德雷克塞尔大学医学院合作建立，为开展艾滋病毒-1/艾滋病神经科学的创新研究提供基础设施。在第二轮资助中，CNAC的中心主题将是通过提供分子和细胞生物学方面的专业知识和服务，以及利用各核心提供的体外、体内和体外系统研究中枢神经系统感染HIV-1的遗传学和病毒学，为开展神经艾滋病的转译研究创造一个环境。我们的目标是促进对手部致病机制的研究，为根除感染细胞和病毒以及艾滋病/中枢神经系统疾病的治疗提供新的途径。因此，将更加重视以细胞和病毒为基础的方法，以及评估艾滋病毒-1对与中枢神经系统疾病有关的细胞功能的影响。为了实现我们的目标，中国科学院将通过其基础科学核心I(BSC I)提供神经细胞培养、病毒试剂、微电极阵列、基因编辑策略和高端蛋白质组/代谢组学方面的专业知识。基础科学核心II(BSC II)将提供专门知识和设施，利用动物模型研究艾滋病毒-1脑相互作用和行为测试/培训以及组织学培训和相关服务。CNAC的临床和转化性研究支持核心(CTRSC)有2,000多名患者参与了坦普尔大学医院(费城北部)和德雷克塞尔的Hahnemann医院(费城中心)的两个具有良好特征/控制的队列，将支持凝聚力IRB协议的开发和维护，提供认知表现和神经心理学、病毒学/免疫学和免疫激活、病毒遗传学/基因组学和生物信息学方面的专业知识。通过发展核心，CNAC将为初级调查人员和临床调查人员提供独特的培训和指导机会，并吸引和发展神经艾滋病领域的医生/科学家。中航中心将通过以下方式提供基础设施：i)通过其发展核心提供启动资金，ii)通过其最先进的基础科学核心提供智力支持和技术服务，以及iii)获得一个运作良好的扩展临床核心，以进行创新研究，以开发智能、有效和安全的遗传和细胞/免疫学策略来治愈艾滋病。此外，通过中航的资金将为坦普尔、德雷克塞尔和大费城地区的其他医疗机构在神经艾滋病方面的合作研究创造一个环境，并扩大其与费城和全国其他艾滋病研究中心的合作。

 DESCRIPTION (provided by applicant): Neurologic complications and related diseases, including HIV-1 associated neurocognitive disorders or HAND, remain one of the most devastating clinical manifestations of HIV-1 infection even after treatment with antiretroviral therapy. Accordingly, it is now well recognized that a novel strategy is needed to eradicate AIDS and its associated co-morbidities as current antiretroviral therapies have failed to eliminate HIV-1 from the infected host. Here, we seek support to continue operation of a highly needed Comprehensive NeuroAIDS Core Center (CNAC) that was established in 2011 at the Temple University School of Medicine in partnership with Drexel University College of Medicine in Philadelphia to provide infrastructure for performing innovative research in the neuroscience of HIV-1/AIDS. The central theme of CNAC, in the second round of funding, will be to foster an environment for performing translational research in neuroAIDS by offering expertise and service in molecular and cellular biology as well as the genetics and virology of HIV-1 infection of the CNS using in vitro, in vivo, and ex vivo systems provided by the various cores. It is our goal that CNAC promotes research toward understanding mechanisms responsible for HAND and provide new paths for the eradication of infected cells and viruses and the treatment of AIDS/CNS disease. Accordingly, more emphasis will be on cell- and viral-based methodologies and the assessment of the impact of HIV-1 on cell function pertaining to CNS diseases. To accomplish our goal, the CNAC will provide expertise in neural cell cultures, viral reagents, microelectrode array, gene editing strategies, and high end proteomics/metabolomics through its Basic Science Core I (BSC I). Basic Science Core II (BSC II) will provide expertise and facilities in the employment of animal models for studying HIV-1 brain interaction and behavioral testing/training and histological training and related services. The Clinical and Translational Research Support Core (CTRSC) of the CNAC, with greater than 2,000 patients participating in two well-characterized/controlled cohorts at Temple University Hospital (North Philadelphia) and Drexel's Hahnemann Hospital (Center City Philadelphia) will support development and maintenance of cohesive IRB protocols, offer expertise in cognitive performance and neuropsychology, virology/immunology and immunoactivation, and viral genetics/genomics and bioinformatics. Through the Developmental Core, the CNAC will offer a unique opportunity for training and mentoring of junior investigators and clinical investigators, and attract and develop physicians/scientists in the field of neuroAIDS. The CNAC will provide infrastructure by i) providing start-up funds through its Developmental Core, ii) offering intellectual support and technical services through its state-of-the-art basic science cores and iii) access to an expansive well-operating clinical core, for conducting innovative research toward the development of intelligent, effective, and safe genetic and cellular/immunologic strategies toward a cure of AIDS. Further, the funding through CNAC will create an environment for the development of collaborative research in neuroAIDS at Temple, Drexel and other medical institutions in the greater Philadelphia area, and extend its collaboration with other AIDS research centers in Philadelphia and the nation.