Monday, October 13, 2025 10/13/2025

Structure and Function of Immune Gene Regulatory Networks

Award Number: R35GM128625
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2018
PERIOD OF PERFORMANCE END DATE: 07/31/2028

Group Awards By:

View Award Description

Structure and Function of Immune Gene Regulatory Networks - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $445,500 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	001	8	7/7/2025	NON-COMPETING CONTINUATION	$445,500
2025	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	7	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $445,500

Issue Date FY: 2024 ( Subtotal = $624,500 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	003	7	9/6/2024	SUPPLEMENT FOR EXPANSION	$179,000
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	002	7	8/2/2024	NON-COMPETING CONTINUATION	$445,500
2024	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	001	6	7/16/2024	COMPETING CONTINUATION	$68,752
2024	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	5	7/16/2024	NON-COMPETING CONTINUATION	-$68,752
														Subtotal = $624,500

Issue Date FY: 2023 ( Subtotal = $445,500 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	001	6	9/20/2023	COMPETING CONTINUATION	$445,500
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	5	9/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $445,500

Issue Date FY: 2022 ( Subtotal = $412,500 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	5	7/19/2022	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2021 ( Subtotal = $412,500 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	4	7/30/2021	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2020 ( Subtotal = $412,500 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	3	7/30/2020	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2019 ( Subtotal = $412,500 )
2019	2019	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	2	7/18/2019	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2018 ( Subtotal = $412,500 )
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	1	8/1/2018	NEW	$412,500
														Subtotal = $412,500

Grand Total All Awards = $3,578,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Structure and Function of Immune Gene Regulatory Networks

Award Number: R35GM128625

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2018

PERIOD OF PERFORMANCE END DATE: 07/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer