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: 8897319
• 负责人: Sabita Roy
• 金额: $ 13.22万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8897319
• 关键词: AIDS Dementia Complex; AIDS/HIV problem; Accounting; Acquired Immunodeficiency Syndrome; Adverse effects; Animal Model; Attenuated; Award; Bacterial Infections; Cells; Chronic; Clinical; Collaborations; Data; Dependency; Development; Disease Progression; Doctor of Philosophy; Drug abuse; Drug usage; Drug user; Educational process of instructing; Epidemic; Epidemiologic Studies; Feedback; Funding; Future; General Population; Goals; Grant; HIV; HIV Infections; HIV-1; Healed; Hepatitis; Hospitalization; Human; Immune; Immunity; Immunosuppression; Impaired wound healing; Infection; Inflammation; Intervention; Investigation; Kansas; Mediating; Mentors; MicroRNAs; Minnesota; Modality; Modeling; Molecular; Morbidity - disease rate; Morphine; Mus; Natural Immunity; Neuroglia; Neuropathogenesis; Operative Surgical Procedures; Opiates; Opioid; Opportunistic Infections; Pain management; Patients; Peripheral; Pharmaceutical Preparations; Pneumonia; Population; Populations at Risk; Predisposition; Prevalence; Process; Proteins; Publishing; Receptor Activation; Reporting; Research; Research Design; Research Personnel; Research Project Grants; Role; Scientist; Senior Scientist Award; Signal Transduction; Societies; Streptococcus pneumoniae; TLR2 gene; TLR4 gene; Testing; Time; Toll-like receptors; Training; Transgenic Animals; Transgenic Mice; Universities; Virus Diseases; Wound Healing; Wound Infection; adaptive immunity; attenuation; co-infection; cytokine; drug abuser; drug of abuse; healing; immune activation; in vivo; intravenous drug user; mouse model; mu opioid receptors; neuroAIDS; novel therapeutics; opioid abuse; professor; skills; statistics

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.

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。在本项目中，我们测试了以下假设：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。