Peripheral blood RNA biomarkers of recovery after spinal cord injury

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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.