# Structure and Function of Immune Gene Regulatory Networks

> **NIH NIH R35** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $445,500

## Abstract

PROJECT SUMMARY
Gene regulatory networks (GRNs) involving interactions between transcription factors (TFs) and cis-
regulatory elements (CREs) are central to most biological processes. Research in my laboratory aims to
characterize the structure and logic of human GRNs with the ultimate goal of devising therapeutic
strategies. Current gaps in our understanding of GRNs include: determining how TF combinations provide
transcriptional specificity, determining how GRNs are rewired in response to environmental cues and
pathogens, and designing strategies to manipulate GRNs to modulate biological outcomes. Cytokines
present an archetype model to study GRNs because cytokines genes are highly regulated at the
transcriptional level in different cell types and stimulation conditions. We have recently delineated a large-
scale cytokine GRN by determining the binding of individual TFs to cytokine promoter regions and
integrating with expression datasets. Here, we will expand these studies to identify the role of
heterodimeric TFs in cytokine regulation by integrating TF-wide screens using a novel heterodimer yeast
one-hybrid approach we developed, and multi-CUT&tag to profile TF heterodimer binding genome-wide.
This will identify the rules by which heterodimers confer transcriptional specificity and will provide targets
for modulation of cytokine expression in disease. Viruses can rewire or leverage host GRNs for productive
viral replication and to evade immune responses. Given the coexistence of viral genomes and host TFs
and host genomes and viral TF within infected cells, this provides the opportunity for viral-host cross-
transcriptional regulation. For example, CREs of DNA viruses and retroviruses can bind host TFs to
regulate viral gene expression in the appropriate cell types and states to promote viral replication or
latency. We will identify the viral CREs from dsDNA viruses and retroviruses that are active in different cell
types and activation states using high-throughput reporter assays, as well as the human TFs that regulate
these viral CREs. Viral TFs can bind to host CREs to modulate the expression of host genes to promote
cell proliferation, metabolic changes, and immune suppression. We will continue to characterize the
function of viral TFs including identifying targets, transcriptional activity, protein-protein interactions, and
changes in transcriptional programs. Altogether, the proposed studies will identify general principles and
generate a framework to study and manipulate immune GRNs, and will identify mechanisms by which
viruses control host GRNs to replicate and evade immune responses.

## Key facts

- **NIH application ID:** 10932103
- **Project number:** 5R35GM128625-07
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Juan Ignacio Fuxman Bass
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $445,500
- **Award type:** 5
- **Project period:** 2018-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932103

## Citation

> US National Institutes of Health, RePORTER application 10932103, Structure and Function of Immune Gene Regulatory Networks (5R35GM128625-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10932103. Licensed CC0.

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