Opioid Drug abuse in the context of opportunistic infection increases susceptibil

阿片类药物滥用会增加机会性感染的易感性

基本信息

  • 批准号:
    8404078
  • 负责人:
  • 金额:
    $ 13.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-08-01 至 2017-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This is an application for a K05 - Senior Scientist Award. The candidate, Dr. Sabita Roy holds a Ph.D. degree from the University of Kansas, Lawrence, and is a Professor in the Basic and translational Division in the Department of Surgery, University of Minnesota. She is currently funded by three independent grants; 1) R01 DA12104: Opioid Abuse, Opportunistic Infection and NeuroAIDS : These studies are designed to investigate if opioid drug abuse and HIV-proteins can either independently or synergistically modulate neuropathogenesis in a S. pneumoniae co-infection model. 2) R01DA031202: Role of microRNAs' in opioid drug abused induced persistent inflammation and HIV Disease Progression. In this project we test the hypothesis that suppression of LPS induced induction of miR-155 and miR-146a, by Morphine and TAT, deregulates the inhibitory feedback loop thus resulting in sustained Toll-Like-Receptor (TLR4) expression and signaling. 3) R01DA022935: Morphine, HIV proteins, wound healing and Infection: The focus of this proposal is to investigate the mechanism by which chronic morphine treatment delays wound healing and if HIV infection further exacerbates the healing process. This K05 award will provide the candidate with release time to expand her research skills and enhance her ability for scientific investigations and mentoring future scientists in drug abuse research. The long-term research goal of the candidate is to explore the molecular and cellular mechanism involved in morphine induced immunosuppression and increased susceptibility to opportunistic infections such as S. pneumonia and HIV/AIDS. The major goal of the current application is to train in HIV/AIDS research as it relates to drug abuse and incorporate this line of research into her ongoing research projects and to introduce state of the art research strategies. To achieve this goal, release time will be utilized for collaborations with HIV/AIDS researchers and researchers with microRNA and TLR expertise. The K05 Award will facilitate this by relieving considerable amount of teaching and administrative duties. This plan has the full support of the Department of Surgery and the University of Minnesota. PUBLIC HEALTH RELEVANCE: The latest statistics on the world epidemic of AIDS & HIV (UNAIDS/WHO, November 2005) report that at least 40 million people are infected with HIV with nearly 6 million cases of AIDS world-wide. There is a strong correlation between chronic drug use and increased susceptibility to HIV infection. Chronic drug users account for approximately a third of all cases of AIDS in the USA and the progression to AIDS dementia is markedly accelerated in opiate drug abusers. This proposal postulates that modulation of microRNAs and Toll like receptors by opioid drug abuse and HIV1-TAT may be a plausible mechanism for the persistent immune activation in these patients. Until now there are no published studies implicating miRs to TLRs' in the dysregulated immune activation observed in HIV infected drug abusing population. These studies will allow for the delineation of the mechanisms and allow for the development of new therapeutic strategies to attenuate immune activation and reverse HIV disease progression both in HIV infected patients and in HIV infected drug abusing population.
描述(由申请人提供):这是 K05 - 高级科学家奖的申请。候选人 Sabita Roy 博士拥有博士学位。拥有堪萨斯大学劳伦斯分校博士学位,是明尼苏达大学外科系基础和转化部门的教授。她目前由三项独立赠款资助; 1) R01 DA12104:阿片类药物滥用、机会性感染和 NeuroAIDS:这些研究旨在调查阿片类药物滥用和 HIV 蛋白是否可以独立或协同调节肺炎链球菌合并感染模型中的神经发病机制。 2) R01DA031202:microRNA 在阿片类药物滥用引起的持续炎症和 HIV 疾病进展中的作用。在这个项目中,我们测试了这样的假设:通过吗啡和 TAT 抑制 LPS 诱导 miR-155 和 miR-146a 的诱导,解除抑制性反馈环路的调节,从而导致 Toll 样受体 (TLR4) 的持续表达和信号转导。 3) R01DA022935:吗啡、HIV 蛋白、伤口愈合和感染:该提案的重点是研究长期吗啡治疗延迟伤口愈合的机制以及 HIV 感染是否进一步加剧愈合过程。该 K05 奖项将为候选人提供释放时间,以扩展她的研究技能,提高她的科学研究能力,并指导未来的药物滥用研究科学家。该候选人的长期研究目标是探索吗啡诱导的免疫抑制和增加对肺炎链球菌和艾滋病毒/艾滋病等机会性感染的易感性的分子和细胞机制。当前申请的主要目标是培训与药物滥用相关的艾滋病毒/艾滋病研究,并将这一研究纳入她正在进行的研究项目,并引入最先进的研究策略。为了实现这一目标,发布时间将用于与 HIV/AIDS 研究人员以及具有 microRNA 和 TLR 专业知识的研究人员进行合作。 K05 奖将通过减轻大量教学和行政职责来促进这一目标。该计划得到了外科系和明尼苏达大学的全力支持。 公共健康相关性:关于世界艾滋病和艾滋病毒流行的最新统计数据(联合国艾滋病规划署/世界卫生组织,2005 年 11 月)报告称,全世界至少有 4000 万人感染了艾滋病毒,其中近 600 万艾滋病病例。长期吸毒与艾滋病毒感染易感性增加之间存在很强的相关性。在美国,慢性吸毒者约占所有艾滋病病例的三分之一,阿片类吸毒者向艾滋病痴呆的进展明显加快。该提议假设阿片类药物滥用和 HIV1-TAT 对 microRNA 和 Toll 样受体的调节可能是这些患者持续免疫激活的合理机制。到目前为止,还没有发表的研究表明在 HIV 感染的药物滥用人群中观察到的免疫激活失调中 miR 与 TLR 相关。这些研究将有助于描述机制,并有助于开发新的治疗策略,以减弱艾滋病毒感染患者和艾滋病毒感染药物滥用人群的免疫激活并逆转艾滋病毒疾病进展。

项目成果

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Sabita Roy其他文献

Sabita Roy的其他文献

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{{ truncateString('Sabita Roy', 18)}}的其他基金

(PQ6) Mesenchymal stem cell based and immunocompetent mouse models of HIV/AIDS KSHV-driven sarcomagenesis
(PQ6) 基于间充质干细胞和免疫活性的 HIV/AIDS 小鼠模型 KSHV 驱动的肉瘤发生
  • 批准号:
    10388236
  • 财政年份:
    2021
  • 资助金额:
    $ 13.22万
  • 项目类别:
(PQ6) Mesenchymal stem cell based and immunocompetent mouse models of HIV/AIDS KSHV-driven sarcomagenesis
(PQ6) 基于间充质干细胞和免疫活性的 HIV/AIDS 小鼠模型 KSHV 驱动的肉瘤发生
  • 批准号:
    10609000
  • 财政年份:
    2021
  • 资助金额:
    $ 13.22万
  • 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
  • 批准号:
    10434855
  • 财政年份:
    2019
  • 资助金额:
    $ 13.22万
  • 项目类别:
Multidisciplinary Training in Substance Abuse Research
药物滥用研究的多学科培训
  • 批准号:
    10395444
  • 财政年份:
    2019
  • 资助金额:
    $ 13.22万
  • 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
  • 批准号:
    10434466
  • 财政年份:
    2019
  • 资助金额:
    $ 13.22万
  • 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
  • 批准号:
    10518777
  • 财政年份:
    2019
  • 资助金额:
    $ 13.22万
  • 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
  • 批准号:
    10653501
  • 财政年份:
    2019
  • 资助金额:
    $ 13.22万
  • 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
  • 批准号:
    10754697
  • 财政年份:
    2019
  • 资助金额:
    $ 13.22万
  • 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
  • 批准号:
    10197088
  • 财政年份:
    2019
  • 资助金额:
    $ 13.22万
  • 项目类别:
Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV
肠道微生物组-脑轴在阿片类药物暴露和 HIV 产生的神经病理学中调节中枢神经系统炎症小体的作用
  • 批准号:
    10020183
  • 财政年份:
    2019
  • 资助金额:
    $ 13.22万
  • 项目类别:

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Role of Autophagy in Microglia-induced NeuroAIDS in Substance Abuse
自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
  • 批准号:
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自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
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自噬在小胶质细胞诱导的药物滥用中的神经艾滋病中的作用
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    8701265
  • 财政年份:
    2013
  • 资助金额:
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Opioid Drug abuse in the context of opportunistic infection increases susceptibil
阿片类药物滥用会增加机会性感染的易感性
  • 批准号:
    8485569
  • 财政年份:
    2012
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HIV遗传多样性和病毒神经发病机制
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