Transcriptional Profiling of the Post-Stroke Immune Response to Tailor Rehabilitation Timelines

PROJECT SUMMARY/ABSTRACT
This R03 proposal is for a 2-year multidisciplinary research project that spans the fields of stroke rehabilitation
and stroke genomics. The central premise in this research is that the transcriptional profiles of circulating immune
cells (peripheral blood mononuclear cells, “PBMCs”) convey information about the severity and progression of
stroke that could be used to inform decisions on the timing of neurorehabilitation. The long-term goal is to use
this information to tailor neurorehabilitation programs based on each patient’s unique biological timeline of
recovery. The key investigators have combined expertise in neurorehabilitation (Dr. Robynne Braun, PI) and
transcriptomics (Dr. Susan Dorsey, Co-I), with further collaborative contributions from the University of Maryland
Stroke Genetics Research Center and the Program in Personalized and Genomic Medicine. By delineating a
chronology of peripheral immune cell responses post-stroke, the results will provide an analytical framework to
identify immunological events associated with post-stroke motor recovery. These studies will fill an existing gap
in the research on recovery-related blood biomarkers for stroke. The proposed research is innovative in pairing
longitudinal transcriptomics with domain-specific measures of stroke recovery and quantitative measures of
corticospinal tract integrity. It is significant for its potential to shift rehabilitation research toward greater
integration of genomic and phenotypic data that ultimately could inform personalized approaches to treatment.
Upon completion of this work we will know: 1) what genes are expressed in peripheral blood mononuclear cells
during the first 30 days post-stroke 2) whether any of these genes are differentially expressed based on the
severity of motor system damage and 3) whether any of these genes align with previously identified biological
phases of stroke recovery in animal models. These findings will furthermore serve as a resource to the broader
rehabilitation research community by providing a rich repository of genomic and phenotypic data accessible
through dbGaP, the Database of Genotypes and Phenotypes.

Grant Number: 1R03HD114143-01
NIH Institute/Center: NIH
Principal Investigator: Robynne Braun