# Deciphering Post-transcriptional gene regulatory networks in cellular stress and innate immunity

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2020 · $392,158

## Abstract

PROJECT SUMMARY
It is the long-term mission of my lab to decipher the critical regulatory networks that govern post-transcriptional
gene regulation during innate immunity with the goal that such knowledge significantly contributes to our
scientific understanding of human health and disease. The innate immune system is comprised of a collection
of environmental sensors and downstream signaling components that orchestrate a response to cellular insults
and stress. A hallmark of innate immune activation is the transcriptional upregulation of the type-I interferons
triggered by the sensing of pathogen-associated or damage-associated molecules. Research on innate
immunity has traditionally focused on understanding the initiating triggers and signal transduction events that
ultimately modulate the expression of a central set of interferons and cytokines. However, much less is
known about the post-transcriptional gene regulatory layer, which acts to refine innate immune
activation at the RNA level – shaping gene expression to allow for a robust but finite host response
while simultaneously preventing aberrant or pathogen-associated gene expression. This is a striking
gap in our understanding given that many aspects of host-pathogen interactions have at its core the detection
and suppression of foreign nucleic acids. It is becoming increasingly clear that RNA-binding proteins (RBPs)
can pre-program the sensitivity of cells to immunogenic stimuli, as well as being essential factors in the anti-
viral response. In part, much of the challenge has been an inability to query this layer of gene regulation in a
comprehensive and systematic way, a necessary prerequisite when it comes to studying RBP biology.
 My training and expertise in RNA/DNA binding protein biochemistry and –omic scale biology has
allowed me to develop the necessary tools and reagents that I have now established in my laboratory to deeply
understand post-transcriptional gene regulation in innate immunity. We are interested in pursuing the
following major biological questions:
 1)How do RNA-binding proteins regulate gene expression of their targets during an innate immune
response?
 2)What is the nature and impact of RNA methylation on mRNAs upon interferon/cGAMP stimulation? And
 how do such changes affect RBP assembly and function?
 3) How are the genomes of RNA viruses deployed during the early stages of infection, and what host- or
 viral-encoded RNA-binding proteins facilitate this process?
 4) What are the regulatory co-factors required for the activating or repressing cGAS-STING signaling? and
 can we identify small molecule compounds for the development of experimental probes and pre-
 therapeutic scaffolds?

## Key facts

- **NIH application ID:** 9931238
- **Project number:** 5R35GM119569-05
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Manuel Ascano
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,158
- **Award type:** 5
- **Project period:** 2016-08-15 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931238

## Citation

> US National Institutes of Health, RePORTER application 9931238, Deciphering Post-transcriptional gene regulatory networks in cellular stress and innate immunity (5R35GM119569-05). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/9931238. Licensed CC0.

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