Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Structure/Function Studies of Enzyme Inhibitors and their Roles in Innate Immune Evasion

Award Number: R35GM140852
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: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2031

Group Awards By:

View Award Description

Structure/Function Studies of Enzyme Inhibitors and their Roles in Innate Immune Evasion - PROJECT SUMMARY/ABSTRACT The innate immune system provides an essential defense against both invading microorganisms and parasitic opportunists. In humans, a robust early innate immune response requires immediate and concerted action by humoral and cellular components, which are represented by the complement system and neutrophils, respectively. Efficient defense against microorganisms and parasites by this “complement/neutrophil axis” is predicated upon a network of molecular interactions as well as biochemical reactions catalyzed by proteases, peroxidases, and related enzyme systems that are activated in response to specific biological triggers. Because complement and neutrophils are among the first host defenses encountered by invading microorganisms and parasites, there is strong selective pressure for them to evolve means to evade complement and neutrophil function. Indeed, work from the last two decades has shown that the pathogen Staphylococcus aureus expresses over 30 different proteins as part of its innate immune evasion repertoire. We have extensively studied S. aureus innate immune evasion from a protein structure/function perspective and found that many such evasion proteins are potent enzyme inhibitors that block proper functioning of the host complement/neutrophil axis. Our recent work on salivary proteins from the blood-feeding sandfly, Lutzomyia longipalpis, strongly suggests that enzyme inhibition is a general principle underlying the phenomenon of innate immune evasion. This MIRA outlines our ongoing research into new modes and mechanisms of inhibiting enzymes that function in the early innate immune system. Our major activities will focus on three broadly related, yet independent avenues of investigation. The first project concerns S. aureus EAP domain proteins. In the prior funding period, we made the surprising discovery that members of this inhibitor family can block two different neutrophil serine proteases simultaneously. We will investigate this observation in more detail, and explore how a particular EAP protein alters the formation and function of neutrophil extracellular traps. The second project concerns the SALO family of proteins from L. longipalpis. In the prior funding period, we unexpectedly found that SALO proteins inhibit the proteolytic reactions needed to cleave pro-proteins into their bioactive counterparts. We will continue our studies on SALO proteins as part of a new line of inquiry. The third project concerns the SPIN family of myeloperoxidase inhibitors secreted by various Staphylococcal species. By using our SPIN data gathered in the prior project period, as well as obtaining complementary new insights on SPINs, we will work to develop a model that defines the physical principles underlying the host species specificity of evasion proteins.


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 = $409,851 )
2026	2026	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	002	6	5/28/2026	COMPETING CONTINUATION	$409,851
2026	2025	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	5	2/13/2026	NON-COMPETING CONTINUATION	$0
2026	2025	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	001	5	5/26/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $409,851

Issue Date FY: 2025 ( Subtotal = $363,312 )
2025	2025	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	001	5	4/3/2025	NON-COMPETING CONTINUATION	$363,312
2025	2024	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	4	11/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $363,312

Issue Date FY: 2024 ( Subtotal = $363,312 )
2024	2024	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	4	2/13/2024	NON-COMPETING CONTINUATION	$326,981
2024	2024	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	001	4	8/6/2024	NON-COMPETING CONTINUATION	$36,331
														Subtotal = $363,312

Issue Date FY: 2023 ( Subtotal = $439,807 )
2023	2023	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	3	3/7/2023	NON-COMPETING CONTINUATION	$363,312
2023	2023	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	001	3	6/5/2023	SUPPLEMENT FOR EXPANSION	$76,495
														Subtotal = $439,807

Issue Date FY: 2022 ( Subtotal = $363,312 )
2022	2022	KANSAS STATE UNIVERSITY	2 FAIRCHILD HALL	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	001	2	6/21/2022	NON-COMPETING CONTINUATION	$36,331
2022	2022	KANSAS STATE UNIVERSITY	2 FAIRCHILD HALL	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	2	2/17/2022	NON-COMPETING CONTINUATION	$326,981
														Subtotal = $363,312

Issue Date FY: 2021 ( Subtotal = $363,312 )
2021	2021	KANSAS STATE UNIVERSITY	2 FAIRCHILD HALL	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	1	4/20/2021	NEW	$363,312
														Subtotal = $363,312

Grand Total All Awards = $2,302,906

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Structure/Function Studies of Enzyme Inhibitors and their Roles in Innate Immune Evasion

Award Number: R35GM140852

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: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer