# Proteomics and Genomics to Identify Therapeutic Targets for Ischemic Stroke Prevention

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $624,583

## Abstract

ABSTRACT
As the global burden of ischemic stroke (IS) continues to rise due to population demographic shifts, new
treatment approaches for stroke prevention are needed to address its public health burden. Survivors of a prior
IS and individuals with atrial fibrillation (AF) are populations at highest risk for future stroke. Current medical
therapies, such as aspirin and lipid lowering treatments, have limited benefit for secondary stroke prevention.
While oral anticoagulation reduces the risk of IS in the setting of AF, the risk of major bleeding and
nonadherence to therapy limits its effectiveness. Multiplexed proteomic profiling technologies have enabled the
measurement of circulating proteins from large populations, and the integration of proteomics with genomic
methods, have the potential to identify proteins that are etiologic factors of IS risk, and therefore potential
targets for prevention. We propose to leverage previously collected plasma samples, genomic data, and
longitudinal electronic medical record data from participants in the Heart and Vascular Health (HVH) Study. By
measuring ~5,300 proteins in 659 IS cases and 972 AF cases using the Olink proteomics platform, we will
evaluate the relationship between individual protein levels with the risk of future IS from up to 25 years of
follow-up. For proteins significantly associated with IS risk, we will use genomic data from the study population
and external cohorts to conduct Mendelian randomization and colocalization analyses to evaluate for evidence
supporting potential causal relationships. Findings will then be replicated in participants of the UK biobank that
have undergone Olink proteomic profiling. For key proteins associated with IS risk, we will develop targeted
immunoassays to facilitate the translation of study findings to clinical settings. The rigorous and efficient
approach described will accelerate the discovery of new etiologic factors and potential treatment targets for IS
prevention.

## Key facts

- **NIH application ID:** 10941500
- **Project number:** 1R01NS138297-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Rizwan Kalani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $624,583
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941500

## Citation

> US National Institutes of Health, RePORTER application 10941500, Proteomics and Genomics to Identify Therapeutic Targets for Ischemic Stroke Prevention (1R01NS138297-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10941500. Licensed CC0.

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