Opioid Drug abuse in the context of opportunistic infection increases susceptibil

描述(申请人提供)：这是一份K05-高级科学家奖的申请书。候选人萨比塔·罗伊博士拥有堪萨斯大学劳伦斯分校的博士学位，是明尼苏达大学外科基础与翻译部的教授。她目前由三个独立的赠款资助：1)R01 DA12104：阿片类药物滥用、机会性感染和神经艾滋病：这些研究旨在调查阿片类药物滥用和艾滋病毒蛋白质是否可以独立或协同地调节肺炎链球菌混合感染模型中的神经发病。2)R01DA031202：microRNAs‘在阿片类药物滥用诱导的持续性炎症和HIV疾病进展中的作用。在本项目中，我们验证了一种假设，即抑制内毒素诱导吗啡和TAT诱导miR-155和miR-146a的产生，解除对抑制反馈环的调节，从而导致Toll样受体(TLR4)的持续表达和信号转导。3)R01DA022935：吗啡，艾滋病毒蛋白，伤口愈合和感染：这项提案的重点是调查慢性吗啡治疗延迟伤口愈合的机制，以及艾滋病毒感染是否进一步加剧愈合过程。这一K05奖项将为候选人提供释放时间，以扩大她的研究技能，增强她的科学调查能力，并在药物滥用研究中指导未来的科学家。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易感性的分子和细胞机制。目前申请的主要目标是在与药物滥用有关的艾滋病毒/艾滋病研究方面进行培训，并将这一研究纳入她正在进行的研究项目，并介绍最新的研究战略。为了实现这一目标，将利用释放时间与艾滋病毒/艾滋病研究人员和具有microRNA和TLR专业知识的研究人员合作。K05奖将通过减轻相当多的教学和行政职责来促进这一点。该计划得到了外科和明尼苏达大学的全力支持。

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.