Comprehensive NeuroHIV Center

综合神经艾滋病毒中心

• 批准号: 10475405
• 负责人: Kamel Khalili
• 金额: $ 150万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-05 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10475405
• 关键词: Achievement; Acute; Address; African American; Anti-Retroviral Agents; Area; Attention; Basic Science; Behavior Disorders; Behavioral; Biodistribution; Bioinformatics; Biological; Biometry; Black race; Brain; CRISPR/Cas technology; Cell Culture Techniques; Cells; Cellular Neurobiology; Cellular biology; Central Nervous System Diseases; Chronic Disease; Clinic; Clinical; Clinical Research; Clustered Regularly Interspaced Short Palindromic Repeats; Cognition Disorders; Collaborations; Communication; Communities; Community Services; DNA; Data; Development; Discipline; Disease; Disease Progression; Employment; Enrollment; Ensure; Equipment and supply inventories; Evaluation; Face; Faculty; Flow Cytometry; Fostering; Funding; Genes; Genomics; Goals; Grant; Guide RNA; HIV; HIV-1; Hispanic; Homeostasis; Human; Human Resources; Image Analysis; Immunologics; Immunophenotyping; In Vitro; Individual; Infection; Infrastructure; Institution; Interdisciplinary Study; Laboratories; Leadership; Longitudinal cohort; Lymphoid Cell; Mental disorders; Mentorship; Methodology; Methods; Molecular; Molecular and Cellular Biology; Monitor; Myeloid Cells; National Institute of Mental Health; Nature; Needs Assessment; Neurocognitive; Neurocognitive Deficit; Neurons; Neuropsychology; Neurosciences; Not Hispanic or Latino; Office of Administrative Management; Organ; Participant; Patients; Performance; Periodicity; Peripheral; Peripheral Blood Mononuclear Cell; Persons; Pharmaceutical Preparations; Phenotype; Philadelphia; Physicians; Population; Preparation; Progress Reports; Prothrombin; Publications; RNA; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Support; Resources; Sampling; Science; Scientist; Secure; Seeds; Services; Site; Surface; Technology; Tissues; Training; Translational Research; Underrepresented Minority; Update; Viral; Viral Genes; Viral Genome; Viral reservoir; Virus; Virus Diseases; Virus Replication; base; base editing; brain cell; brain dysfunction; career; cohort; community based research; community partnership; comorbidity; data management; deep sequencing; design; experimental study; fitness; genetic approach; genome analysis; genome editing; health disparity; immune function; improved; innovation; interest; lymphoid organ; meetings; member; microscopic imaging; neuroAIDS; neurobehavioral; neurocognitive disorder; neuropsychiatry; new technology; next generation; novel strategies; operation; outreach; pandemic disease; patient oriented research; prevent; programs; quantitative imaging; side effect; social; social structure; stem; viral DNA; virus genetics; web site

SUMMARY Current treatment of HIV-1 infection has changed the face of the disease by converting a once acute deadly disease to a chronic illness. As such, many other issues have surfaced that require close attention including comorbidities associated with the presence of the viral genome, as well as the potential side effects of ART on several tissues and cells including brain that impact on the homeostasis of neuronal cells thus contributing to neurocognitive and behavioral disorders seen among people living with HIV (PWH). Other areas of concern relate to social and structural determinants of NeuroHIV disparities in the PWH community. Now, it has become increasingly clear that the landscape must move toward a cure by employing sophisticated, innovative, next generation approaches and technologies that are aimed at the permanent elimination of HIV-1 in PWH and protect uninfected individuals from HIV-1 infection at the cellular and molecular levels. Importantly, a parallel approach to improve neurocognitive/psychological disorders in the HIV community as well as the use of molecular strategies for elimination/protection must be implemented to end more than four decades of clinical challenges caused by HIV-1 infection. By combining resources and expertise of our teams at Temple and Drexel, we have developed a Comprehensive NeuroHIV Center (CNHC) facility to provide services to scientists from the greater Philadelphia area and beyond to initiate and investigate the current issues associated with neuroscience of HIV-1 from community to laboratory and clinic with an emphasis on neuropsychiatric/behavioral (a new area of emphasis), continued studies on the neuroscience of HIV-1 infection, and the development of cure strategies at the molecular and cellular levels by the elimination of HIV-1 proviral DNA from the host using a genetic approach such as CRISPR gene editing-based technologies. We propose that this unique and unprecedented strategy will have dual benefit in improving current challenges associated with HIV-1 infection in PWH community and offer new opportunities for the development of a novel approach for mitigation/elimination of viral infection by a highly collaborative and complementary group of scientists. Our goals remain to provide neuroHIV research infrastructure and support utilizing and expanding the CNHC's rich clinical neuropsychological data from a longitudinal cohort of PWH, including primarily Black/African-American and White participants that identify as non-Hispanic or Hispanic origin well-characterized by deep sequencing and detailed immunophenotyping as described in the Clinical and Translational Research Support Core (CTRSC), working closely with NeuroHIV Community Partnership and Disparities Core (NHCPDC) and taking advantage of the expert services offered by Viral Gene Editing and Bioinformatics Core (VGEBC), together with resources offered by the Cell Biology and Functional Analysis Core (CBFAC), and the financial and intellectual opportunities offered by the Developmental Research and Mentorship Core (DRMC). All of which are operationally optimized and orchestrated by the Central Administrative and Management Core (CAMC) to maximize our achievements.

总结 目前对HIV-1感染的治疗已经改变了这种疾病的面貌， 从疾病到慢性病。因此，出现了许多其他问题，需要密切关注，包括 与病毒基因组的存在相关的合并症，以及ART的潜在副作用， 包括脑在内的几种组织和细胞影响神经元细胞的稳态，从而有助于 神经认知和行为障碍见于艾滋病毒感染者（PWH）。其他关切领域 与PWH社区NeuroHIV差异的社会和结构决定因素有关。现已成为 越来越清楚的是，景观必须走向治愈，采用先进的，创新的，下一个 旨在永久消除威尔斯亲王医院的HIV-1的方法和技术， 在细胞和分子水平上保护未感染的个体免受HIV-1感染。重要的是， 改善艾滋病毒社区神经认知/心理障碍的方法以及使用 必须实施消除/保护的分子策略，以结束四十多年的临床 HIV-1感染带来的挑战。通过结合坦普尔和德雷克塞尔团队的资源和专业知识， 我们已经建立了一个综合性的神经艾滋病病毒中心（CNHC）设施，为来自世界各地的科学家提供服务。 大费城地区和超越发起和调查与神经科学相关的当前问题 从社区到实验室和诊所，重点是神经精神/行为（一个新的领域 继续进行HIV-1感染的神经科学研究，并制定治疗策略 在分子和细胞水平上，通过使用遗传学方法从宿主中消除HIV-1前病毒DNA， 例如基于CRISPR基因编辑的技术。我们建议，这一独特的和前所未有的 有关策略对改善威尔斯亲王医院社区目前与爱滋病病毒-1感染有关挑战有双重好处 并为开发减轻/消除病毒感染的新方法提供了新的机会 由一群高度合作互补的科学家组成我们的目标仍然是提供神经HIV研究 基础设施和支持利用和扩展CNHC丰富的临床神经心理学数据， PWH的纵向队列，主要包括黑人/非洲裔美国人和白色参与者，他们认为自己是 非西班牙裔或西班牙裔来源通过深度测序和详细的免疫表型得到充分表征， 与NeuroHIV密切合作的临床和转化研究支持核心（CTRSC）中所述 社区伙伴关系和差异核心（NHCPDC），并利用 病毒基因编辑和生物信息学核心（VGEBC），以及细胞生物学提供的资源， 功能分析核心（CBFAC），以及发展中心提供的财政和智力机会， 研究和指导核心（DRMC）。所有这些都是由中央情报局优化和协调的 行政和管理核心（CAMC），以最大限度地提高我们的成就。