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.

Public Health Relevance

This project will use advanced RNA sequencing of peripheral white blood cells from acutely spinal cord injured rats to seek RNA expression biomarkers that can predict long term outcomes and serve as indicators of therapeutic efficacy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS106981-01A1
Application #
9687191
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Jakeman, Lyn B
Project Start
2018-08-15
Project End
2020-07-31
Budget Start
2018-08-15
Budget End
2019-07-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118