# Effect of stored blood on sphingosine-1-phosphate mediated vascular barrier integrity

> **NIH NIH K08** · UNIVERSITY OF CINCINNATI · 2020 · $198,013

## Abstract

Project Summary
 The proposed Career Development Award will provide the Candidate, Amy T. Makley,
MD, with the means to attain independence as a scientific investigator. Dr. Makley’s ultimate
research goals are to become an independent surgeon scientist investigating the downstream
effects of resuscitation with stored blood products following hemorrhagic shock.
 The research project proposed in this application focuses on the immense clinical problem
of morbidity and mortality following traumatic injury. Specifically, up to 50% of deaths from
hemorrhage are potentially preventable. While the mainstay of treatment of hemorrhage includes
transfusion of stored blood components, knowledge remains limited regarding the effects of
stored blood transfusion on the development of complications including acute lung injury. This
study aims to investigate the effects of resuscitation with stored blood, ultimately targeting the
breakdown of the pulmonary endothelial barrier and development of acute lung injury after
hemorrhage. Sphingosine-1-phosphate (S1P) and its primary endothelial receptor, sphingosine-
1-phosphate receptor subtype-1 (S1PR1) have integral roles in the preservation of the endothelial
barrier, and preliminary data supports a disruption of S1P homeostasis after exposure to stored
blood. The experimental design proposed in this application will elucidate the mechanisms by
which S1P and its receptor are affected following exposure to stored blood, using both an in vivo
model of traumatic injury and hemorrhagic shock in mice as well as an in vitro model of pulmonary-
specific human and murine endothelial cell monolayers.
 The Career Development Plan outlined in this proposal includes a robust mentorship team
led by Dr. Timothy Pritts and Dr. Alex Lentsch, as well as a formal Scholarship Oversight
Committee (SOC) including Drs. Michael Edwards, Charles Caldwell, and Erich Gulbins. An in-
depth program of additional training in molecular biology under the tutelage of the SOC is
proposed to augment Dr. Makley’s experiences and aid in her development. In addition, a
reduction in her clinical and educational administrative responsibilities is proposed to provide her
with 75% protected research time. She has access to outstanding research facilities and
equipment to complete all of the proposed experiments in this application. Dr. Makley has the
complete and unwavering support of her Chair, Division, and Department of Surgery at the
University of Cincinnati to succeed in her endeavor to become an independent scientist.

## Key facts

- **NIH application ID:** 9998969
- **Project number:** 5K08GM126316-03
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Amy T Makley
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,013
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998969

## Citation

> US National Institutes of Health, RePORTER application 9998969, Effect of stored blood on sphingosine-1-phosphate mediated vascular barrier integrity (5K08GM126316-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9998969. Licensed CC0.

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