# Signaling activation and constraints in maintaining immune homeostasis

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $390,000

## Abstract

The innate immune system detects pathogen-derived molecules to prevent infections via specialized immune
receptors. The immune receptors include cell surface-resident pattern recognition receptors (PRRs), such as
Toll-like receptors (TLRs) in mammals and receptor kinases (RKs) in plants, and intracellular NOD-like
receptors (NLRs) in plants and mammals. Plant PRRs detect conserved pathogen-associated molecular
patterns (PAMPs), whereas NLRs recognize pathogen-specific effectors, culminating in a unified immune
system. How the signaling networks underlying PRR- and NLR-mediated immunity are interconnected remains
largely unknown. In addition, defects or over-activation of immune receptors could lead to cell death or
autoimmunity. Thus, understanding the mechanisms that enable or constrain PRR and NLR activation for
maintaining immune homeostasis is particularly important. The PI’s laboratory has developed a series of
sensitive and high-throughput genetic screens to dissect the complex activation and signaling mechanisms in
plant immunity, and revealed the importance of malectin-like RKs (MLRs) as a molecular module at the plasma
membrane linking PRR and NLR immune receptors. PI’s long-term goal is to elucidate the signaling networks
regulating innate immune responses using Arabidopsis as a model system and expand the knowledge of how
hosts fend off infections without causing autoimmune disorders. The proposed research rooted in PI’s previous
discoveries and preliminary studies will support a series of projects that address several critical knowledge
gaps in two interrelated research areas. First, the research will elucidate how the PRR- and NLR-mediated
signaling pathways converge into an interconnected and balanced immune response. Specifically, the projects
will mechanistically address how a PRR-activated MAP kinase cascade regulates NLR-mediated immune
homeostasis through MLRs perceiving different peptide ligands. Second, the research will decipher the
immune gene orchestration through the combinatorial action of the layered transcriptional, posttranscriptional,
and posttranslational regulations at the single-cell level. The projects will focus on how intertwined
posttranslational modifications, including ADP-ribosylation, ubiquitination, and phosphorylation, regulate
immune-specific gene transcription, stability, and translation. The proposed interdisciplinary research will
provide ample training opportunities for diverse undergraduate and graduate students and postdoctoral fellows.

## Key facts

- **NIH application ID:** 10884188
- **Project number:** 5R35GM149197-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ping He
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884188

## Citation

> US National Institutes of Health, RePORTER application 10884188, Signaling activation and constraints in maintaining immune homeostasis (5R35GM149197-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10884188. Licensed CC0.

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