Biomarkers in an HIV-1 Infected Drug Abusing Clinical Cohort

HIV-1感染和甲基苯丙胺（METH）对中枢神经系统具有破坏性影响 （CMS）。此外，药物滥用往往与艾滋病毒-1感染有关， 共享治疗这些患者是一个非常复杂的过程，因为它必须针对两个实体， 在本质上完全不同。尽管有大量的研究工作，认知的潜在机制， HIV-1感染或甲基苯丙胺使用所造成损害还远未了解。我们认为， 蛋白质组学技术可能导致新的疾病标记和对疾病过程的重要见解。我们 假设血浆样本的蛋白质组成包含独特的蛋白质组学特征 （指纹）。对来自停止使用甲羟色胺的患者的此类样本进行分析将导致 确定和更好地理解可逆性的分子机制（短期） 以及HIV-1感染和METH之间相互作用的不可逆（长期）效应。的 该提案的优势在于其精心挑选和明确定义的临床材料队列，跟踪记录 经过验证和成功使用创新和技术先进的“尖端”蛋白质组学 方法，跨学科研究小组，基于蛋白质组学的先前发展， 生物标志物发现和功能蛋白质组学平台，独家使用所需的“尖端” 强大的研究和协作环境。 目标1.确定血浆蛋白质组谱的差异，以反映短期和长期 甲基化的退出。这一目标的工作反映了血浆中含有显著的 检测中枢神经系统暴露于药物滥用（METH）的HIV感染蛋白标志物， 更好地理解潜在的分子机制。 目标2.为了证实未被发现的生物标志物在肿瘤的分子机制中的相关性， HIV-1感染和METH使用协同作用。这一目标的长期目标是验证 对HIV和METH对CNS的同时作用具有特异性的标记物，将用于未来， 重点突出的假设驱动项目。 这项工作的公共卫生相关性涉及艾滋病毒感染者与艾滋病患者的重叠人群， 使用METH的人。血液中蛋白质生物标志物的发现将使研究有害的 在艾滋病毒感染情况下使用甲基苯丙胺的效果，从而加强教育工作，改进诊断， 和治疗进展。

HIV-1 infection and methamphetamine (METH) have devastating effects on the central nervous system (CMS). Moreover, drug abuse is very often associated with HIV-1 infection as a consequence of needle sharing. Treatment of these patients is a very complex process because it has to target two entities which are quite different in nature. Despite substantive research efforts, the mechanisms underlying cognitive impairment resulting from HIV-1 infection or METH use are far from understood. We posit that advances in proteomic techniques could lead to new markers of disease and critical insights into disease processes. We hypothesize that the protein composition of plasma samples contains unique proteomic signatures (fingerprints). Profiling of such samples from patients who stopped using METH will lead to identification and better understanding of molecular mechanisms underlying reversible (short-term) and non-reversible (long-term) effects of the interactions between HIV-1 infection and METH. The strengths of this proposal lie in its carefully selected and well defined cohort of clinical material, track record of a proven and successful use of innovative and technologically advanced "cutting edge" proteomic approaches, the interdisciplinary group of investigators, the prior development of proteomics-based biomarker discovery and functional proteomics platforms, the exclusive use of needed "cutting edge" equipment, and strong research and collaborative environment. Aim 1. To determine differences in proteome profiles of plasma which reflect short- and long-term withdrawal of METH. The work in this aim reflects the hypothesis that plasma contains in significant measure protein markers of HIV infection of CNS exposed to drug of abuse (METH), which could be used for better understanding of underlying molecular mechanisms. Aim 2. To substantiate the relevance of uncovered biomarkers in molecular mechanisms of the synergistic effect of HIV-1 infection and use of METH. The long-term goal of this aim is to validate iomarkers specific for concurrent effect of HIV and METH on the CNS which will be used for future, more 'focused and hypothesis driven projects. The public health relevance of this work relates to the overlapping populations of HIV infected people with those who use METH. Discovery of protein biomarkers in the blood will enable the study of the harmful effects of METH in the setting of HIV infection, leading to increased education efforts, improved diagnostics, and therapeutic inroads.