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Transcriptomic Signatures of Ischemic Stroke: Unlocking Human-Specific Targets for Cerebroprotection

Award Number: K23NS146687
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/08/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Transcriptomic Signatures of Ischemic Stroke: Unlocking Human-Specific Targets for Cerebroprotection - PROJECT SUMMARY/ABSTRACT While endovascular thrombectomy (EVT) has revolutionized the treatment of acute ischemic stroke caused by large vessel occlusion (LVO), 54% of patients still experience severe disability or death. This variability in outcomes highlights a critical gap in stroke management, which primarily focuses on restoring blood flow but fails to address the downstream molecular events that drive continued neuronal injury. Decades of preclinical research have sought to bridge this gap, identifying over 1,000 potential cerebroprotective drug targets. However, the failure to translate these findings into clinical success raises concerns about the validity of cellular and animal models in stroke research. The overarching goal of this study is to identify and validate cerebroprotective drug targets in humans by directly sampling blood within the ischemic vasculature during active ischemia. To achieve this, we will leverage the high EVT volume at Barnes-Jewish Hospital/Washington University School of Medicine (WUSM) and the endovascular approach of the intervention to collect 40 paired periprocedural arterial blood samples: 1) Pre-thrombus: From the femoral artery at the time of groin puncture; 2) Post-thrombus: From distal to the occluded cerebral vessel, obtained via microcatheter advancement through the thrombus on first pass. I hypothesize that post-thrombus blood, sampled adjacent to ischemic tissue, will reveal a cellular and molecular milieu distinct from peripheral circulation, providing clinically relevant, human-specific cerebroprotective drug targets. This hypothesis and the feasibility of this collection technique are supported by a pilot study conducted during my NINDS T32 vascular neurology fellowship at the University of Cincinnati. Further demonstrating feasibility, pre/post-thrombus sample collection is already underway as part of my KL2 Career Development Award at WUSM, through the establishment of a deeply phenotyped, prospective EVT biorepository. Supported by WUSM’s vast research community, this study will: 1) Define ischemic cellular transcriptomes in post- vs. pre- thrombus arterial blood samples using single-cell RNA sequencing; 2) Determine whether a unique post- thrombus gene expression signature is associated with clinical neurologic improvement or deterioration in LVO patients; 3) Evaluate the drug target potential of identified gene expression signatures using network-based analyses and bioinformatics (exploratory). The data generated will be widely shared to accelerate drug target discovery and has the potential to make a significant impact by identifying highly translatable therapeutic targets. This study will provide critical protected time, funding, and mentored guidance from leaders in cerebrovascular injury, computational transcriptomics, and neuroimmunology, equipping me with the expertise to achieve my long-term career goal: Establish an independent, NIH-funded research program focused on bridging the translational gap in stroke and delivering effective cerebroprotective therapies to clinical practice. Additionally, the robust dataset generated by this study, combined with my KL2 biorepository, will lay the foundation for future independent multi-omic grant proposals that I plan to submit in the final years of this award.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $231,264 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/7/2026	NEW	$231,264
														Subtotal = $231,264

Grand Total All Awards = $231,264

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Transcriptomic Signatures of Ischemic Stroke: Unlocking Human-Specific Targets for Cerebroprotection

Award Number: K23NS146687

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/08/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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