# Investigation of enterovirus D68 pathogenesis in the human spinal cord

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $154,602

## Abstract

Megan Freeman, MD, PhD, is a Pediatric Infectious Diseases (ID) Fellow at the University of Pittsburgh
Medical Center (UPMC) Children’s Hospital of Pittsburgh (CHP). She earned MD and PhD degrees at
Vanderbilt University where she investigated the cell biology and pathogenesis of coronavirus infection (Mark
Denison, MD). After clinical training in Pediatrics and Pediatric ID at CHP, she joined the lab of Carolyn Coyne,
PhD, an expert in enteroviruses and tissue barriers to viral infections. Her research focused on understanding
enterovirus D68 (EV-D68) pathogenesis, the hypothesized cause of acute flaccid myelitis (AFM), a polio-like
syndrome of paralysis in previously healthy children. Dr. Freeman used intestinal organoids and primary
bronchial epithelial cells to show that some contemporary EV-D68 isolates associated with AFM were able to
use the intestinal tract for replication in addition to the respiratory tract, suggesting an alternate infection route.
This work formed the basis for the spinal cord organoid model featured in this proposal.
 Dr. Freeman will build on >10 years of experience studying viral-host interactions while gaining new
proficiencies in immunology, neuroscience, and imaging techniques which will facilitate her transition into an
independently-funded pediatrician-scientist. Dr. Freeman has assembled a multidisciplinary mentorship and
advisory team, chaired by primary mentor Dr. John Williams (respiratory virus immunity/pathogenesis) and co-
mentor Dr. Terence Dermody (viral pathogenesis/encephalitis). Additional advisory members include Dr.
Carolyn Coyne (enteroviruses/organoids), Dr. Philana Lin (immunology) and Dr. Clayton Wiley
(neuroscience/encephalitis). The committee will facilitate technique acquisition, career development, and
collaborations. The training plan incorporates coursework, technical expertise, skills in written and oral
communication, responsible conduct of research, presentation at conferences, and a timeline for seeking
additional funding. The University of Pittsburgh School of Medicine is an outstanding training environment due
to the record of scientific achievement, resources, commitment to physician scientists, and expertise.
 AFM peaked biennially from 2012-2018 coincident with EV-D68 circulation, however, reasons why
contemporary EV-D68 targets the nervous system are unknown. The central hypothesis of this proposal is that
contemporary strains of EV-D68 directly infect motor neurons of the spinal cord, resulting in neuronal damage
and paralysis. Using an innovative human spinal cord organoid model, the Aims will 1) define spinal cord
replication of EV-D68, identify infected cell type(s), and discover contributions to pathogenesis, 2) define the
host cellular response of spinal cord organoids to infection with EV-D68, and 3) evaluate glutamate alterations
during infection of spinal cord organoids with EV-D68. The studies in this proposal utilize advanced tissue
modeling and imaging techniques, v...

## Key facts

- **NIH application ID:** 10879000
- **Project number:** 5K08AI171177-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Megan Culler Freeman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $154,602
- **Award type:** 5
- **Project period:** 2022-07-06 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879000

## Citation

> US National Institutes of Health, RePORTER application 10879000, Investigation of enterovirus D68 pathogenesis in the human spinal cord (5K08AI171177-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10879000. Licensed CC0.

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