# Translational approaches to unravel organ-specific microvascular endothelial responses in sepsis.

> **NIH GM R35** · CINCINNATI CHILDRENS HOSP MED CTR · 2026 · $389,997

## Abstract

Translational approaches to unravel organ-specific microvascular endothelial responses in sepsis.
PROGRAM SUMMARY:
 Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an
infection and is associated with high mortality. Systemic inflammation and endothelial activation with resultant
microvascular leak, thromboses, and hypoxic tissue injury are hallmarks of sepsis. Yet, in over 100 trials, drugs
aimed at modulating cascades of inflammation and coagulation have not proven to be efficacious. The primary
reason for this failure is attributed to clinical and biological variability among critically ill patients. More recently,
high-throughput approaches including gene-expression profiling have shown promise in disentangling patient-
level heterogeneity in the host immune response. In contrast, sampling challenges coupled with cell and organ
level heterogeneity have impeded a similar understanding of the host endothelial response. It follows that
translational approaches that shed light on human microvascular pathobiology may lead to the discovery of
targeted therapies that restore tissue homeostasis and shift sepsis care paradigms toward organ recovery.
 My research program seeks to address key knowledge gaps that currently impede scientific progress
through projects spanning 3 domains. 1) DISCOVERY: The endothelium in patients remains inaccessible.
Moreover, while endothelial heterogeneity and organ-specificity are increasingly recognized, their contribution
to the evolution of organ dysfunctions remains poorly understood. To address this, we will enrich circulating
endothelial cells from whole blood of children with septic shock with the primary objective of developing a
transcriptomic atlas at single-cell resolution. By comparing signatures of circulating endothelial subsets from
patients, relative to published datasets of tissue-resident endothelial cells, we will identify organ-specific targets
for future hypotheses testi

## Key facts

- **NIH application ID:** 11322575
- **Project number:** 5R35GM155165-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Mihir R Atreya
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $389,997
- **Award type:** 5
- **Project period:** 2024-07-01T00:00:00 → 2029-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11322575

## Citation

> US National Institutes of Health, RePORTER application 11322575, Translational approaches to unravel organ-specific microvascular endothelial responses in sepsis. (5R35GM155165-03). Retrieved via AI Analytics 2026-05-17 from https://api.ai-analytics.org/grant/nih/11322575. Licensed CC0.

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