HIV activation in secondary pulmonary infection

描述(由申请人提供)：我是一名临床调查员，对肺部感染的病理生物学有研究兴趣。我对通过支气管肺泡灌洗获得的临床样本进行分子分析，然后在模型系统中进行机制研究。这一方法卓有成效，在培训临床研究人员方面也很有效。我的研究得到了2个R01基金的支持。“HIV/TB在肺中的相互作用”研究了一种假说，即静息的肺泡巨噬细胞表达一组转录抑制因子，通常会抑制HIV在肺部的复制。在结核病(TB)期间，炎症细胞被招募到肺部，接触巨噬细胞，并降低对HIV-1 LTR的抑制。炎症细胞中的可溶性因子随后激活转录。这两个步骤的过程对于在结核病患者中观察到的艾滋病毒-1的高水平复制是必要的，也是充分的。另一项最近由R01资助的研究，我是该研究的合作者，名为“HIV相关细菌性肺炎的纵向研究”。这项研究扩展了实验室调查细菌性肺炎的工作。第二项研究的假设是，接受抗逆转录病毒治疗的艾滋病毒阳性患者将继续发展为细菌性肺炎和其他肺部感染，这将导致肺部特有的细胞募集和激活。这一过程将促进艾滋病毒-1的复制和变异，加速艾滋病的进程。这项纵向研究是这笔赠款研究部分的主题。我目前在临床服务上花费了45%的精力。K24职业生涯中期研究人员奖将使我能够将患者护理责任减少到10%的努力，因此我可以将重点放在培训下一代临床调查人员上。我将能够将我可以在翻译研究中充分指导的医生数量增加两倍。K24奖项的第二个目标是获得传染病流行病学培训，并进入哥伦比亚大学公共卫生硕士课程。这种教学经验将加强我与流行病学家的合作，并使我能够学习分析大型数据集所需的量化技术。K24奖项提供的支持将增强我参与转换研究计划的潜力，这些计划开发有效的新策略，以改善对患有继发性肺部感染的艾滋病毒感染患者的护理。

DESCRIPTION (provided by applicant): I am a clinical investigator with a research interest in the pathobiology of pulmonary infections. I perform molecular assays on clinical samples obtained by bronchoalveolar lavage and then conduct mechanistic studies in model systems. This approach has been productive and has been effective in training clinical investigators. My research is supported by 2 R01 grants. "HIV/TB Interaction in the Lung" investigates the hypothesis that resting alveolar macrophages express a set of transcriptional repressers that normally inhibit HIV replication in the lung. During tuberculosis (TB), inflammatory cells are recruited to the lung, contact macrophages, and derepress the HIV-1 LTR. Soluble factors from the inflammatory cells then activate transcription. This 2-step process is necessary and sufficient for the high-level replication of HIV-1 observed in persons with TB. A second recently funded R01-supported study, for which I am a co-Pi, is titled "Longitudinal Studies of HIV-Associated Bacterial Pneumonia." This study extends the work of the laboratory to investigate bacterial pneumonia. The hypothesis of this second study is that HIV-positive individuals receiving antiretroviral therapy will continue to develop bacterial pneumonia and other pulmonary infections that will lead to characteristic cellular recruitment and activation in the lung. This process will enhance HIV-1 replication and mutation, accelerating the course of AIDS. The longitudinal study is the subject of the research section of this grant. I currently spend 45% effort in clinical service. The K24 Midcareer Investigator Award in Patient-Oriented Research would enable me to reduce patient care responsibilities to 10% effort, so I can increase my focus on training the next generation of clinical investigators. I will be able to increase by 2-fold the number of physicians who I can adequately mentor in translational research. A second goal of the K24 award is to obtain training in infectious diseases epidemiology and matriculate in the MPH program at Columbia University. This didactic experience will enhance my collaboration with epidemiologists and will allow me to learn the quantitative techniques required to analyze large data sets. The support provide by the K24 award will enhance my potential to participate in translational research programs that develop effective novel strategies for the improved care of HIV-infected patients with secondary pulmonary infections.