# Exosomal-mediated pyroptosis in ventilation-associated preterm brain injury

> **NIH NIH K08** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $155,520

## Abstract

ABSTRACT
This proposal describes a five-year training program and research proposal for the career development of Dr.
Augusto Schmidt as a physician-scientist in Neonatology with expertise in neonatal brain injury. Dr. Schmidt
completed his Pediatrics residency and Neonatology fellowship at Cincinnati Children’s Hospital and is currently
Assistant Professor of Pediatrics in the Division of Neonatology at the University of Miami (UM). Dr. Schmidt is
interested in determining the mechanistic relationship between mechanical ventilation and brain injury in preterm
newborns, and is particularly interested in how mechanical ventilation causes the lung to release exosomes,
which may induce brain cellular death and injury in preterm newborns. Dr. Schmidt will be mentored by Dr. Dalton
Dietrich and Dr. Shu Wu with the support of a scientific advisory committee. Dr. Dietrich, a world-renowned
expert in brain injury, will mentor Dr. Schmidt’s scientific progress and career development. Dr. Dietrich is the
Director of the Miami Project to Cure Paralysis and Distinguished Chair of Neurosurgery at UM and has been
committed to training scientists throughout his career having served as the principal investigator of a T32 Training
Program, thesis advisor of 9 PhD students, and mentored over 30 postdoctoral fellows. Dr. Wu is a neonatologist
and expert in neonatal lung injury and will complement Dr. Dietrich as a co-mentor. Dr. Wu has successfully
mentored more than 20 clinical and postdoctoral fellows and medical students. The advisory committee will
support Dr. Dietrich and Dr. Wu in mentoring Dr. Schmidt and will consist of Dr. Roberta Brambilla, an expert in
neuroinflammation, Dr. Eduardo Bancalari, a neonatologist and expert in neonatal chronic lung disease and Dr.
Alan Jobe, a neonatologist and accomplished physician-scientist, who has previously mentored Dr. Schmidt. In
this proposal, Dr. Schmidt will test the hypothesis that mechanical ventilation causes the lung to release
exosomes containing caspase-1 and that these exosomes cross the blood-brain barrier to activate Gasdermin
D (GSDMD) in the brain, inducing cellular death and brain injury. Dr. Schmidt will use a survival model of neonatal
rodent ventilation to test the following aims: (1) to determine the mechanistic function of GSDMD in inducing
neuronal cell death in ventilation-associated brain injury (VABI); (2) to determine the mechanistic function of
pulmonary-derived exosomal caspase-1 in activating neuronal GSDMD in VABI. Dr. Schmidt will use a
combination of pharmacological and genetic loss-of function mice models for GSDMD and caspase-1 to address
these aims. Brain injury and cellular death will be determined by a combination of techniques including
immunohistochemistry, western blotting, ELISA, and real time-PCR. Long-term outcomes will be assessed by
neurobehavioral testing. These pharmacological and genetic approaches will delineate the role of the exosomal
caspase-1 / neuronal GSDMD pathwa...

## Key facts

- **NIH application ID:** 10039670
- **Project number:** 1K08HD102718-01
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Augusto F Santos Schmidt
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,520
- **Award type:** 1
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039670

## Citation

> US National Institutes of Health, RePORTER application 10039670, Exosomal-mediated pyroptosis in ventilation-associated preterm brain injury (1K08HD102718-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10039670. Licensed CC0.

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