Tuesday, March 17, 2026 3/17/2026

Linking Human TB Genetic Susceptibility Loci to Granuloma Biology

Award Number: R01AI166304
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/11/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

Linking Human TB Genetic Susceptibility Loci to Granuloma Biology - Abstract Mycobacterium tuberculosis kills approximately 1.4 million people annually. People exposed to similar initial doses may have very different outcomes, ranging from clearance to active disease to subclinical or latent infection. A central structure of tuberculosis, the granuloma represents a key interface between pathogen and host, and its dynamics contribute to disease outcome. Granuloma macrophages induce expression of an unusual epithelioid program that dictates granuloma structure and infection trajectory. Due to a lack of genetically tractable animal models that fully reproduce key aspects of granuloma biology – namely, epithelioid transformation and necrosis – many aspects of granuloma formation have not been probed. Genome-wide association studies in humans have identified several potential TB susceptibility loci, but the mechanisms by which these genes act, particularly within the granuloma, are not well understood. Here we will link established human genetic susceptibility loci to the biology of mycobacterial granulomas. We will use murine, zebrafish, and explant models of bona fide mycobacterial granulomas to directly probe granuloma structure, epithelioid state, immune and drug access and granuloma dynamics. Using single cell transcriptional profiling and host and bacterial mutants, we have defined a repertoire of diverse cell types and transcriptional states that contribute to the physiological properties of the mycobacterial granuloma. We will define how alteration of host immune pathways identified in genome-wide human genetic studies alter granuloma biology through murine and zebrafish models that recapitulate key properties of human granulomas, including caseation necrosis and epithelioid transformation. We will validate these findings in human TB granuloma specimens. Finally, we will use comprehensive TnSeq profiling using saturating Mtb transposon libraries to define the interplay between bacteria and host within the context of the tuberculous granuloma. Overall, these approaches will lead to a fuller understanding of granuloma biology as well as new opportunities for therapeutic interventions.


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: 2026 ( Subtotal = $692,604 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	5	1/1/2026	NON-COMPETING CONTINUATION	$692,604
														Subtotal = $692,604

Issue Date FY: 2025 ( Subtotal = $671,827 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	4	12/19/2024	NON-COMPETING CONTINUATION	$671,827
														Subtotal = $671,827

Issue Date FY: 2024 ( Subtotal = $692,606 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	001	3	5/21/2024	NON-COMPETING CONTINUATION	$69,261
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	3	1/3/2024	NON-COMPETING CONTINUATION	$623,345
														Subtotal = $692,606

Issue Date FY: 2023 ( Subtotal = $692,654 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	2	1/13/2023	NON-COMPETING CONTINUATION	$692,654
														Subtotal = $692,654

Issue Date FY: 2022 ( Subtotal = $692,701 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Allergy and Infectious Diseases Research	000	1	1/10/2022	NEW	$692,701
														Subtotal = $692,701

Grand Total All Awards = $3,442,392

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Linking Human TB Genetic Susceptibility Loci to Granuloma Biology

Award Number: R01AI166304

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/11/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer