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

描述（由申请人提供）：K02独立科学家奖将使候选人能够在弗吉尼亚联邦大学（VCU）获得最大的保护时间，以从事NIDA资助的药物滥用- 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，候选人主持了P01 DA19398，“阿片类药物滥用和CNS对HIV的脆弱性”，是R0I DA18633，“阿片类药物-HIV的机制：诱导的神经变性”的首席研究员，是R01 DA024461，“神经胶质前细胞作为HIV/阿片类药物相互作用的靶点”的合作者，是NIDA R03研究阿片类药物-丙型肝炎病毒（HCV）相互作用病理学的合作者，并且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；星形胶质细胞和少突胶质细胞中阿片受体的细胞基础及其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。申请人建立了全球合作，继续优化阿片类药物滥用- hiv -1合并症的方法，指导了非常成功的博士后，基础和临床教师；包括负责任的研究行为（RCR）方面的培训，共同指导了NIDA培训补助金，并组织了促进药物滥用研究的地方和国际会议。K02奖将使候选人能够：(1)追求当前资助的目标，同时开发药物滥用（例如，自我给药范例），HlV-1（人源SCID小鼠模型）和分子神经病毒学的前沿方法；(2)通过与VCU HIV/AIDS中心和VCU/Johns Hopkins university NIDA联合CTN的转化研究，将基础和临床方法结合起来；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强调RCR）。他被VCU的药理学和毒理学部门招募来追求这些目标，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，而且候选人还发现阿片类药物内在地促进了艾滋病毒的神经退行性作用。候选人恭敬地要求该奖项投入更多的时间来研究阿片类药物滥用-艾滋病毒相互作用的机制，以确定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.