# Role of Autophagy in Mesenchymal Stromal Cells During Sepsis

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $196,760

## Abstract

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 aims, preparation of manuscripts,...

## Key facts

- **NIH application ID:** 10004108
- **Project number:** 5K08GM126313-04
- **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:** $196,760
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004108

## Citation

> US National Institutes of Health, RePORTER application 10004108, Role of Autophagy in Mesenchymal Stromal Cells During Sepsis (5K08GM126313-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10004108. Licensed CC0.

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