# Systemic and Local Immune Function after Pediatric Thermal Injury

> **NIH NIH K08** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2021 · $188,460

## Abstract

PROJECT SUMMARY/ABSTRACT
Given the prevalence and morbidity of pediatric thermal injury it is imperative that we completely understand
and define all knowledge gaps related to this disease. The immunobiology of pediatric burn injury is not well
defined and if understood can unlock the doors to novel therapeutic targets. My prior research training, current
research advisory committee, strong mentorship and practice as a pediatric burn surgeon will allow me to
obtain data and help close this knowledge gap. The overall objective of this proposal is to further develop my
career into a surgeon-scientist whose focus is on the immunobiology of pediatric thermal injury with goals of
using immunomodulation therapy to decrease adverse outcomes. Using methods validated in other forms of
pediatric critical illness we will test our central hypothesis that upregulation of the PD-1 pathway is
associated with immune suppression and adverse outcomes following pediatric burn injury; and that
this immune suppression is reversible ex vivo through the use of PD-1 pathway inhibitors. Thermally
injured children will undergo longitudinal blood sampling as well as tissue bed sampling at the time of
debridement and grafting procedures. Leukocyte expression of PD-1/PD-L1/L2 will be quantified by flow
cytometry. Innate and adaptive immune function will be measured by ex vivo stimulation assays and flow
cytometry. Wound bed macrophage expression of PD-1/PD-L1/L2 will be measured along with pro-
inflammatory and anti-inflammatory phenotypic markers using immunohistochemistry and laser capture
microdissection with mRNA profiling. Furthermore, we will determine if the immune suppressive effects of
thermal injury are reversible using ex vivo methods. We will co-incubate peripheral blood leukocytes from
thermally injured children with inhibitors of the PD-1 pathway, GM-CSF or recombinant IL-7. Cells will then be
evaluated for restoration of immune function via ex vivo stimulation assays and flow cytometry. This study will
be the first to evaluate the role of the PD-1 pathway with respect to pediatric thermal injury. This is of particular
importance given the clinical implications of immune checkpoint inhibitors in other forms of disease such as
cancer and sepsis. This career development award will generate further preliminary data and also provide me
with the tools necessary to successfully compete for future independent funding in areas of pediatric thermal
injury.

## Key facts

- **NIH application ID:** 10242660
- **Project number:** 5K08GM124499-04
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Rajan Thakkar
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,460
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242660

## Citation

> US National Institutes of Health, RePORTER application 10242660, Systemic and Local Immune Function after Pediatric Thermal Injury (5K08GM124499-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242660. Licensed CC0.

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