Opioid Drug abuse in the context of opportunistic infection increases susceptibil

描述（由申请人提供）：这是一份申请K05 -高级科学家奖的申请书。候选人Sabita Roy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和转化部的教授。她目前由三个独立基金资助；1) R01 DA12104：阿片类药物滥用，机会性感染和神经aids：这些研究旨在研究阿片类药物滥用和hiv蛋白是否可以单独或协同调节肺炎链球菌共感染模型中的神经发病机制。2) R01DA031202: microrna '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。在这个项目中，我们检验了一个假设，即吗啡和TAT抑制LPS诱导miR-155和miR-146a的诱导，解除了抑制反馈回路，从而导致toll样受体（TLR4）的持续表达和信号传导。3) R01DA022935：吗啡，HIV蛋白，伤口愈合和感染：本提案的重点是研究慢性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奖将为候选人提供释放时间，以扩大她的研究技能，提高她的科学调查能力，并指导未来的科学家进行药物滥用研究。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HIV/AIDS等机会性感染的易感性的分子和细胞机制。目前申请的主要目标是培训与药物滥用有关的艾滋病毒/艾滋病研究，并将这方面的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，将利用释放时间与艾滋病毒/艾滋病研究人员以及具有microRNA和TLR专业知识的研究人员合作。K05奖将减轻相当多的教学和行政责任，从而促进这方面的工作。这个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. 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.