Peripheral blood RNA biomarkers of recovery after spinal cord injury

项目摘要 脊髓损伤（SCI）是一种破坏性的疾病，它极大地改变了患者的生活， 虽然SCI的第一次诊断发生在4,000多年前， 治疗SCI患者。此外，SCI研究领域缺乏生物标志物， 用于i）评估损伤的初始严重程度，这是确定下游损伤的主要因素。 行动过程，和/或ii）用于预测患者的长期神经恢复。 我们的研究小组和其他研究人员已经证明，SCI会产生全身性炎症反应， 细胞和分子水平。然而，血液或脑脊液（CSF）中SCI的假定生物标志物 在验证研究中通常无法重复。这些发现类似于其他领域（例如精神病学） 最初对候选基因进行了不成功的假设驱动的研究，然后转向偏差较小的研究。 高通量方法，如基因组学、转录组学和蛋白质组学。 该项目将测试假设，即白色血细胞（WBC）的转录组含有重要的 关于SCI的严重程度和进展的信息。我们试图通过以下方式破译这些“加密”信息： 在SCI的临床前大鼠模型中利用高通量RNAseq技术。我们将测试我们的假设， 以下具体目标： 目的1：我们将使用RNAseq定量不同急性期大鼠WBC中所有基因的表达水平， 和亚急性时间点。 目标2：我们将使用先进的生物信息学来发现白细胞中受白细胞分化影响的基因模块。 SCI的严重程度和/或长期神经恢复。 我们希望这项研究将在大鼠模型系统中产生新的SCI生物标志物，并将随后用于 作为人体验证研究的基础。

PROJECT SUMMARY Spinal cord injury (SCI) is a devastating condition that dramatically alters the lives of the patients who suffer from it. Although the first diagnosis of SCI occurred more than 4,000 years ago, there is still no efficient treatment for people suffering from SCI. In addition, the field of SCI research lacks biomarkers that can be utilized i) towards assessing the initial severity of the injury, a major factor in determining the downstream course of action, and/or ii) for predicting the long-term neurological recovery of the patient. Our group and others have shown that SCI generates a systemic inflammatory response that is detectable at cellular and molecular levels. However, putative biomarkers of SCI in blood or cerebrospinal fluid (CSF) have generally failed to replicate in validation studies. These findings are analogous to other fields (e.g. psychiatry) that initially pursued unsuccessful hypothesis-driven studies of candidate genes before turning to less biased high-throughput methods such as genomics, transcriptomics, and proteomics. This project will test the hypothesis that the transcriptomes of white blood cells (WBCs) contain important information about the severity and progression of SCI. We seek to decipher this “encrypted” information by utilizing high-throughput RNAseq technology in a preclinical rat model of SCI. We will test our hypothesis with the following Specific Aims: Aim 1: We will use RNAseq to quantify the expression levels of all genes in rat WBCs at different acute and sub-acute timepoints after SCI. Aim 2: We will use advanced bioinformatics to discover gene modules in WBCs that are affected by the severity of SCI and/or the long-term neurological recovery. We expect that this study will yield novel biomarkers of SCI in a rat model system, and will subsequently serve as the basis for validation studies in humans.