Friday, November 14, 2025 11/14/2025

Transcriptional networks governing A. fumigatus virulence

Award Number: R01AI162802
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: 09/22/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

Group Awards By:

View Award Description

Transcriptional networks governing A. fumigatus virulence - Abstract Invasive infections due to Aspergillus fumigatus are increasing and are still associated with unacceptably high mortality, even with new therapies. Our understanding of A. fumigatus infection biology is limited. Among 10,180 predicted genes in the A. fumigatus genome, over 95% are uncharacterized, and fewer than 100 genes have demonstrated roles in virulence. It is critical to identify genes that govern virulence and the pathways in which they act because they can point to high priority targets for therapeutic and diagnostic development. We have identified a transcriptional regulator in A. fumigatus, WrpA, that shares limited homology with Candida albicans Wor1 and Histoplasma capsulatum Ryp1. Our preliminary data indicate that WrpA governs the capacity of A. fumigatus to withstand macrophage killing, grow under hypoxic conditions, and invade and damage pulmonary cells in vitro. ΔwrpA deletion mutants have highly attenuated virulence in the mouse model of invasive aspergillosis. Using RNA-seq, we found that WrpA governs the expression of ~15% of genes in the A. fumigatus genome, including multiple transcription factor genes. Our premise is that the WrpA is a master regulator that governs host cell interactions and virulence. In support of this premise, our initial investigations of the WrpA regulon have already revealed novel pathogenicity-related functions of three WrpA-dependent transcription factors, SrbB, Fcr1, and Ndt80. Our goal is to characterize the WrpA regulon in A. fumigatus and to identify downstream effector genes whose products mediate pathogenicity by: 1) identifying the transcription factors that are directly regulated by WrpA and determining their roles in pathogenicity; 2) analyzing selected WrpA- dependent transcription factors and identifying their downstream target genes; and 3) determining the function of effector genes controlled by the WrpA regulon and investigating their roles in virulence. The results of the experiments described in this proposal will enable us to characterize a key transcriptional regulator that governs A. fumigatus pathogenicity and then use this information to identify downstream effector genes, the products of which mediate host cell interactions and virulence. The results of this work will not only provide foundational understanding of A. fumigatus virulence mechanisms, but also hold promise to identify new diagnostic, therapeutic, and vaccine targets.


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 = $657,546 )
2025	2025	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST BLDG MRL	TORRANCE	CA	90502	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	5	7/22/2025	NON-COMPETING CONTINUATION	$657,546
														Subtotal = $657,546

Issue Date FY: 2024 ( Subtotal = $657,546 )
2024	2024	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST BLDG MRL	TORRANCE	CA	90502	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	4	8/12/2024	NON-COMPETING CONTINUATION	$657,546
														Subtotal = $657,546

Issue Date FY: 2023 ( Subtotal = $657,546 )
2023	2023	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST	TORRANCE	CA	90502	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	3	7/26/2023	NON-COMPETING CONTINUATION	$657,546
														Subtotal = $657,546

Issue Date FY: 2022 ( Subtotal = $657,546 )
2022	2022	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 W CARSON ST	TORRANCE	CA	90502	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	8/19/2022	NON-COMPETING CONTINUATION	$657,546
														Subtotal = $657,546

Issue Date FY: 2021 ( Subtotal = $671,071 )
2021	2021	LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER	1124 WEST CARSON ST.	TORRANCE	CA	90502	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	9/22/2021	NEW	$671,071
														Subtotal = $671,071

Grand Total All Awards = $3,301,255

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Transcriptional networks governing A. fumigatus virulence

Award Number: R01AI162802

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: 09/22/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer