# Network Dissection of Host-Pathogen Interactions in Mycobacterium tuberculosis Infection

> **NIH NIH DP2** · SEATTLE CHILDREN'S HOSPITAL · 2021 · $565,500

## Abstract

ABSTRACT
Infection is a dynamic interplay between host and pathogen, coordinated through each organism's signaling and
gene regulatory networks. The world's deadliest pathogen, Mycobacterium tuberculosis (Mtb), can exploit its
network of molecular interactions with the host to elicit an infection steady state that enables it to persist
asymptomatically for up to decades. Perturbations in Mtb's or the host's network activities that tip the balance of
this molecular homeostasis will alter infection outcomes: either pathogenically toward a symptomatic tuberculosis
(TB) disease with rampant Mtb growth and pathological inflammation that could lead to death, or protectively
toward infection clearance. I will dissect host signaling and Mtb regulatory network activities for infection fate-
deciding tipping-point genes that impact Mtb viability and host inflammation during infection in primary human
monocyte-derived macrophages (MDMs), a major infected host cell in vivo. I will profile the host and pathogen
transcriptional responses to these infection-altering perturbations to define molecular mechanisms underlying
the host-pathogen interplay, and I will use this information to identify synergistic joint interventions that
concurrently target host and pathogen. Identifying these tipping-point genes at the host-pathogen interface
should inform new therapeutic intervention strategies that jointly target host and pathogen to elicit host protection,
while also revealing fundamental insights into pathogenesis.

## Key facts

- **NIH application ID:** 10294557
- **Project number:** 1DP2AI164249-01
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Shuyi Ma
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $565,500
- **Award type:** 1
- **Project period:** 2021-08-03 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294557

## Citation

> US National Institutes of Health, RePORTER application 10294557, Network Dissection of Host-Pathogen Interactions in Mycobacterium tuberculosis Infection (1DP2AI164249-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10294557. Licensed CC0.

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