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Elucidating the function of astacin metalloproteinases during host invasion in the skin-penetrating nematode Strongyloides stercoralis

Award Number: F31AI197560
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Elucidating the function of astacin metalloproteinases during host invasion in the skin-penetrating nematode Strongyloides stercoralis - PROJECT SUMMARY The goal of this project is to determine the role of astacin metalloproteinases during host invasion in the soil- dwelling human threadworm Strongyloides stercoralis. S. stercoralis infects over 610 million individuals globally, predominantly in tropical and sub-tropical areas. Infections can cause chronic, debilitating conditions such as gastrointestinal distress and malnutrition, and fatal infections can occur in immunocompromised individuals. There are currently no prophylactics for the prevention of strongyloidiasis. Infection occurs when individuals encounter soil-dwelling infective third-stage larvae (iL3s), typically while walking barefoot through fecal- contaminated soil, and the iL3s enter the body by penetrating through the skin. Although skin penetration is a critical step of the parasitic life cycle, the molecular mechanisms that mediate skin penetration are poorly understood. Digestive proteases in the parasite’s excretory-secretory product (ESP) have long been proposed to be essential for skin penetration, but this hypothesis has not been directly tested. Astacins comprise a large family of zinc metalloproteinases, several of which are highly abundant in the ESP of S. stercoralis iL3. One of these astacins, named strongylastacin, has been implicated indirectly in skin penetration based on its ability to digest collagen in vitro. The overall goal of this proposal is to elucidate the role of strongylastacin, and other astacins highly expressed in the ESP of iL3s, during skin penetration using cutting-edge approaches for generating stable transgenic and knockout strains of S. stercoralis. Aim 1 will investigate the spatial expression patterns of these astacin genes, as well as the corresponding proteins, to gain insight into when and how astacins are secreted into the environment. Aim 2 will investigate the functional requirement for these astacins during host invasion. Groups of astacin genes will be deleted using CRISPR, and the ability of knockout iL3s to penetrate skin will be quantified using ex vivo skin-penetration assays with rat and human skin. Together, the results from this project will provide important insights into how skin-penetrating nematodes invade their hosts and may identify novel targets for the development of effective prophylactics.


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 = $47,187 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	1	4/3/2026	NEW	$0
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	4/3/2026	NEW	$47,187
														Subtotal = $47,187

Grand Total All Awards = $47,187

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Elucidating the function of astacin metalloproteinases during host invasion in the skin-penetrating nematode Strongyloides stercoralis

Award Number: F31AI197560

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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