Neuron-Glia Mechanisms & Interactions Underlying Opioid Abuse-HIV-1 Comorbidity

描述(由申请者提供)：K02独立科学家奖将使候选人能够在弗吉尼亚联邦大学(VCU)获得最长的保护时间，以从事NIDA资助的关于药物滥用-HIV-1共病的研究，获得先进的跨学科专业知识，并指导该领域的学生和教师科学家。药物滥用和艾滋病毒-1是相互关联的流行病，具有可怕的后果。为了解决这个问题，候选人指导了P01 DA19398拨款，“阿片类药物滥用和中枢神经系统对艾滋病毒的易感性”，是R0I DA18633拨款的首席研究员，“阿片类药物-艾滋病毒：诱导的神经变性的机制”，是R01 DA024461的联合L，“作为艾滋病毒/阿片类药物相互作用的靶标的神经胶质前体细胞”，是NIDA R03拨款的联合研究员，研究阿片类药物与丙型肝炎病毒的相互作用的病理学，并是许多其他项目的顾问。申请人发表的开创性研究表明：阿片类药物可以直接影响中枢神经系统的成熟；阿片类药物受体的细胞基础和星形胶质细胞和少突胶质细胞的功能；阿片类药物本质上加剧了神经艾滋病的发病机制-确定了神经元和多种胶质细胞类型的细胞内和细胞间病理机制。申请者建立了全球合作，继续优化阿片类药物滥用-艾滋病毒-1共病的方法，指导了非常成功的博士后和博士后以及基础和临床教师；包括负责任的研究行为(RCR)培训，共同指导了NIDA培训赠款，并组织了促进药物滥用研究的地方和国际会议。K02奖项将使候选人能够：(1)追求现有拨款的目标，同时开发药物滥用(如自我给药范例)、HLV-1(人源化SCID小鼠模型)和分子神经病毒学的尖端方法；(2)通过与VCU艾滋病毒/艾滋病中心和VCU/约翰斯·霍普金斯大学的联合翻译研究，将基础和临床方法结合起来。NIDA CTN；同时继续指导学生/早期职业科学家(包括代表性不足的个人和对RCR的重视)。他被部门招募到VCU。药理学和毒理学研究所致力于实现这些目标，并得到了巨大的支持。公共卫生相关性：阿片类药物(海洛因)滥用和艾滋病毒/艾滋病是相互关联的流行病。药物滥用不仅会传播艾滋病毒，候选人还发现阿片类药物本质上促进了艾滋病毒的神经退化效应。候选人敬请该奖项投入更多时间研究阿片类药物滥用与艾滋病毒相互作用的潜在机制，以确定治疗阿片类药物滥用和神经艾滋病的新疗法。

DESCRIPTION (provided by applicant): A K02 independent Scientist Award will enable the candidate to obtain maximum protected time at Virginia Commonwealth University (VCU) to pursue NIDA funded research on substance abuse-HIV-1 comorbidity, acquire advanced cross-disciplinary expertise, and to mentor student and faculty scientists in this area. Drug abuse and HIV-1 are interlinked epidemics with horrific consequences. To address this problem, the candidate directs grant P01 DA19398, "Opiate drug abuse and CNS vulnerability to HIV", is Principal Investigator (PI) on grant R0I DA18633, "Mechanisms of opiate drug-HIV: lnduced neurodegeneration", is a co-l on R01 DA024461, "Glial progenitors as targets of HIV/opiate interactions", is a co-l on a pending NIDA R03 grant to study opioid drug-hepatitis C virus (HCV) interactive pathology, and is a consultant on numerous other projects. The applicant has published seminal studies demonstrating: that opioids can directly affect CNS maturation; the cellular basis of opioid receptor and function in astrocytes and oligodendrocytes; and that opioids intrinsically exacerbate the pathogenesis of neuroAIDS-identifying both intra- and intercellular pathologic mechanisms in neurons and multiple glial types. The applicant has established worldwide collaborations that continue to optimize approaches to opioid abuse-HIV-1 comorbidity, has mentored highly successful pre- and postdoctoral, and basic and clinical faculty; including training in the responsible conduct of research (RCR), has co-directed a NIDA training grant, and organized local and international conferences promoting substance abuse research. A K02 award will enable the candidate to: (1) pursue the goals of current grants, while developing cutting-edge approaches to substance abuse (e.g., self-administration paradigms), HlV-1 (humanized SCID mouse model), and molecular neurovirology; (2) to merge basic and clinical approaches through translational research with the VCU HIV/AIDS Center and joint VCU/Johns Hopkins Univ. NIDA CTN; while continuing to mentor students/early career scientists (including under-represented individuals and an emphasis on RCR). He was recruited to VCU by the Dept. of Pharmacology and Toxicology to pursue these goals and receives tremendous support for this endeavor. PUBLIC HEALTH RELEVANCE: Opioid (heroin) abuse and HIV/AIDS are interrelated epidemics. Not only does drug abuse spread HIV, but also the candidate discovered that opioids intrinsically promote the neurodegenerative effects of HIV. The candidate respectfully requests this award to devote more time to pursue research into the mechanisms underlying opioid drug abuse-HIV interactions to indentify new therapies for opioid abuse and neuroAIDS.