Peripheral blood RNA biomarkers of recovery after spinal cord injury

项目总结 脊髓损伤(Sci)是一种毁灭性的疾病，它极大地改变了患者的生活。 从它那里。尽管脊髓损伤的第一次诊断发生在4000多年前，但仍然没有有效的方法 对脊髓损伤患者的治疗。此外，脊髓损伤研究领域缺乏可以 用于评估损伤的初始严重程度，这是确定下游的一个主要因素 行动方案，和/或ii)用于预测患者的长期神经康复。 我们的团队和其他人已经证明，脊髓损伤会产生一种全身炎症反应，可以在 细胞和分子水平。然而，血液或脑脊液(CSF)中可能存在的脊髓损伤生物标志物 在验证性研究中普遍未能复制。这些发现与其他领域(如精神病学)类似。 它最初对候选基因进行了不成功的假设驱动的研究，后来转向了不那么偏颇的研究 高通量方法，如基因组学、转录组学和蛋白质组学。 这个项目将检验这样的假设，即白血球(WBC)的转录本含有重要的 有关脊髓损伤的严重程度和进展的信息。我们试图通过以下方式破译这种“加密的”信息 在临床前脊髓损伤大鼠模型中利用高通量RNAseq技术。我们将使用以下工具来验证我们的假设 以下是具体目标： 目的1：我们将使用RNAseq定量检测不同急性发作期大鼠白细胞中所有基因的表达水平。 脊髓损伤后的亚急性时点。 目标2：我们将使用先进的生物信息学来发现WBC中受 脊髓损伤的严重程度和/或长期的神经康复。 我们预计这项研究将在大鼠模型系统中产生新的脊髓损伤生物标志物，并将随后提供服务 作为对人体进行验证研究的基础。

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.