# Role of Autophagy in Mesenchymal Stromal Cells During Sepsis

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $53,999

## Abstract

UNCHANGED from parent grant - This K08 proposal describes a five-year research and training plan that
will facilitate the transition of Dr. Sailaja Ghanta to an independent academic researcher in the field of sepsis
and cell therapy. Dr. Ghanta has a strong background in basic research and has completed post-graduate
training in neonatal-perinatal medicine. Sepsis is a leading cause of morbidity and mortality in intensive care
units. Investigations of neonatal septic responses have lagged behind adults. Thus, the candidate's proposal
initially focuses on using well-characterized adult models of sepsis and she will transition to independence by
translating the knowledge gained from this award to neonatal sepsis. Mesenchymal stromal cells (MSCs), an
ideal candidate for a therapeutic, improve survival in murine sepsis by modulating the immune response and
producing specialized pro-resolving lipid mediators (SPMs) that promote the resolution of inflammation. MSC
efficacy in sepsis may be limited by the oxidative inflammatory microenvironment into which they are
administered. As the candidate previously showed, intact autophagy is necessary for MSC survival under
oxidative stress. The overarching aim of this proposal is to delineate the role of autophagy in MSCs during
sepsis with the long-term goal of modulating autophagy in MSCs to prolong their survival in oxidative
environments and optimize MSC therapy for sepsis. The hypothesis that autophagy is necessary for MSC-
mediated immunomodulation in sepsis will be tested with the following specific aims: 1. Investigate the
importance of the autophagy pathway for the therapeutic effects of MSCs in murine sepsis, 2. Decipher
the autophagy dependent effect on the resolution of inflammation by MSCs during sepsis, 3. Determine
whether MSCs can improve the outcome of autophagy protein deficient mice during sepsis. This
research has significance, as knowledge gained from this study will impact future cell-based therapeutics for
the devastating condition of sepsis. Dr. Ghanta will receive mentorship from her scholarship oversight
committee composed of distinguished scientists with expertise related to key areas of this proposal including
immune responses, autophagy, MSCs, and SPM biology. The training opportunities and resources at Brigham
and Women's Hospital (BWH) and Harvard Medical School are an ideal environment for the candidate's career
development program. The Department of Pediatric Newborn Medicine at BWH is committed to Dr. Ghanta's
success and has assured at least 75% protected time to devote to the activities described in this proposal. The
candidate's mentor, Dr. Mark Perrella, is a NIH funded researcher in the field of sepsis and cell therapy. A
detailed career development and training plan is presented that includes mentored research, didactic
coursework, self-directed readings, seminars, and presentations at scientific meetings. The candidate details a
timeline for completion of the research ai...

## Key facts

- **NIH application ID:** 10192012
- **Project number:** 3K08GM126313-04S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Sailaja Ghanta
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $53,999
- **Award type:** 3
- **Project period:** 2017-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192012

## Citation

> US National Institutes of Health, RePORTER application 10192012, Role of Autophagy in Mesenchymal Stromal Cells During Sepsis (3K08GM126313-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10192012. Licensed CC0.

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