Comprehensive NeuroHIV Center

综合神经艾滋病毒中心

• 批准号: 10615173
• 负责人: Kamel Khalili
• 金额: $ 148.79万
• 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/10615173
• 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; Disparity; Employment; Enrollment; Ensure; Equipment and supply inventories; Evaluation; Face; Faculty; Flow Cytometry; Fostering; Funding; Genes; Genomics; Goals; Grant; Guide RNA; HIV; HIV-1; HIV-associated neurocognitive disorder; 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; Neurons; Neuropsychology; Neurosciences; Not Hispanic or Latino; Organ; Participant; Patients; Performance; Periodicals; Peripheral; Persons; Pharmaceutical Preparations; Phenotype; Philadelphia; Physicians; Population; Preparation; Progress Reports; Publications; RNA; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Support; Resources; Sampling; Science; Scientist; Secure; Services; Site; Surface; Technology; Tissues; Training; Translational Research; Underrepresented Minority; Update; Viral; Viral Genes; Viral Genome; Viral reservoir; Virus; Virus Diseases; Virus Replication; base editing; 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; scientific organization; side effect; social; social determinants; stem; structural determinants; 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.

概括 HIV-1感染的当前治疗方法通过转化曾经急性致命而改变了疾病的表面 患有慢性疾病的疾病。因此，许多其他问题浮出水面，需要密切关注，包括 与病毒基因组的存在以及艺术的潜在副作用有关的合并症 几个组织和细胞，包括影响神经元细胞稳态的大脑，从而有助于 在艾滋病毒（PWH）中看到的神经认知和行为障碍。其他关注的领域 与PWH社区中神经hiv差异的社会和结构决定因素有关。现在，它已经变成了 越来越清楚的是，景观必须采用复杂，创新的，接下来的 旨在永久消除PWH中HIV-1的生成方法和技术 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，平行 改善艾滋病毒社区中神经认知/心理疾病的方法以及使用 必须实施消除/保护的分子策略，以结束超过四十年的临床 HIV-1感染引起的挑战。通过将我们在Temple and Drexel团队的资源和专业知识相结合， 我们已经开发了一个综合的神经hiv中心（CNHC）设施，以向来自的科学家提供服务 大费城地区及以外的地区，以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的HIV-1，重点是神经精神病/行为（一个新领域 强调），对HIV-1感染的神经科学的持续研究以及治愈策略的发展 在分子和细胞水平上，通过使用遗传从宿主中消除HIV-1前病毒DNA 诸如基于CRISPR基因编辑的技术之类的方法。我们建议这种独特而前所未有的 策略将在改善PWH社区中与HIV-1感染相关的当前挑战方面具有双重好处 并为开发一种新型方法提供缓解/消除病毒感染的新机会 由高度协作和互补的科学家小组。我们的目标仍然可以提供Neurohiv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，包括主要是黑人/非裔美国人和白人参与者 非西班牙裔或西班牙裔起源通过深度测序和详细的免疫表型来表征 在临床和翻译研究支持核心（CTRSC）中描述，与NeuroHiv紧密合作 社区伙伴关系和差异核心（NHCPDC）并利用专家服务 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）以及发展性提供的财务和智力机会 研究与指导核心（DRMC）。所有这些都在操作中优化和精心策划 行政和管理核心（CAMC），以最大化我们的成就。

项目成果

Complement and HIV-I infection/HIV-associated neurocognitive disorders.

• DOI: 10.1007/s13365-014-0243-9
• 发表时间: 2014-04
• 期刊: JOURNAL OF NEUROVIROLOGY
• 影响因子: 3.2
• 作者: Liu, Fengming;Dai, Shen;Gordon, Jennifer;Qin, Xuebin
• 通讯作者: Qin, Xuebin

Pur-alpha regulates RhoA developmental expression and downstream signaling.

• DOI: 10.1002/jcp.24105
• 发表时间: 2013-01
• 期刊: Journal of cellular physiology
• 影响因子: 5.6
• 作者: Mishra M;Del Valle L;Otte J;Darbinian N;Gordon J
• 通讯作者: Gordon J

Interplay of Rad51 with NF-κB pathway stimulates expression of HIV-1.

• DOI: 10.1371/journal.pone.0098304
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kaminski R;Wollebo HS;Datta PK;White MK;Amini S;Khalili K
• 通讯作者: Khalili K

Epigenetic regulation of polyomavirus JC.

多瘤病毒 JC 的表观遗传调控。

• DOI: 10.1186/1743-422x-10-264
• 发表时间: 2013
• 期刊: Virology journal
• 影响因子: 4.8
• 作者: Wollebo,HassenS;Woldemichaele,Baheru;Khalili,Kamel;Safak,Mahmut;White,MartynK
• 通讯作者: White,MartynK

SIV-Mediated Synaptic Dysfunction Is Associated with an Increase in Synapsin Site 1 Phosphorylation and Impaired PP2A Activity.

SIV 介导的突触功能障碍与突触蛋白位点 1 磷酸化增加和 PP2A 活性受损有关。

• DOI: 10.1523/jneurosci.0178-19.2019
• 发表时间: 2019
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Shekarabi,Masoud;Robinson,JakeA;Smith,MandyD;Burdo,TriciaH
• 通讯作者: Burdo,TriciaH