Friday, December 12, 2025 12/12/2025

Drug Target Discovery, Validation, and Prioritization for Schistosomiasis

Award Number: R01AI167967
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: 12/20/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Drug Target Discovery, Validation, and Prioritization for Schistosomiasis - Schistosomes infect 200 million of the world’s poorest people. Although these parasites kill 250,000 people annually, and rob millions more the ability to lead healthy and productive lives, treatment of schistosome infection relies on a single drug (Praziquantel). Unfortunately, Praziquantel is not a magic bullet. Indeed, praziquantel is not equally effective against all intramammalian stages of the parasite’s life cycle and it suffers from a variable cure rate in some endemic settings. This later point, raises the specter that praziquantel-resistant parasites could emerge as organizations ramp up mass drug administration programs. Indeed, several studies have demonstrated that strains with reduced sensitivity to praziquantel can be rapidly selected in the laboratory. Therefore, efforts to develop the next generation of antischistosome therapies to replace praziquantel are key to a sustained effort to eradicate this disease. Drug development efforts against schistosomes suffer from two important limitations. First, the large size of the adult parasites (~1cm in length) makes screening thousands of compounds for activity against the worm impractical. The second important limitation is that we only know the function of a small number of proteins in these worms making it challenging conduct informed target-based drug discovery efforts. To address these issues, we have conducted the first large-scale loss-of-function RNA interference (RNAi) screen in adult schistosomes. Using this platform, we have performed over 2000 individual RNAi knockdown experiments in adult Schistosoma mansoni and identified nearly two hundred genes, a large fraction of which are potentially druggable, that are essential for parasite survival and/or neuromuscular function both in vitro and in vivo inside mice. To capitalize on these studies we will execute three specific aims to discover and experimentally prioritize druggable targets in the schistosome. In Specific Aim 1, we will utilize RNAi and in silico approaches to identify and prioritize druggable targets that are essential in vitro and in vivo in three medically relevant schistosome species. In Specific Aim 2, we will experimentally validate the druggability of the highest priority targets from Aim 1 by assessing the performance of these targets in small-scale high throughput small molecule screens. These studies will identify both validated druggable targets in the schistosome that can form the basis of future drug discovery campaigns and compounds poised for lead optimization efforts.


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 = $819,288 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	4	12/3/2025	NON-COMPETING CONTINUATION	$819,288
														Subtotal = $819,288

Issue Date FY: 2025 ( Subtotal = $819,288 )
2025	2025	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	3	12/2/2024	NON-COMPETING CONTINUATION	$819,288
														Subtotal = $819,288

Issue Date FY: 2024 ( Subtotal = $819,288 )
2024	2024	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	2	11/15/2023	NON-COMPETING CONTINUATION	$737,359
2024	2024	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	001	2	5/14/2024	NON-COMPETING CONTINUATION	$81,929
														Subtotal = $819,288

Issue Date FY: 2023 ( Subtotal = $819,288 )
2023	2023	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Allergy and Infectious Diseases Research	000	1	12/20/2022	NEW	$819,288
														Subtotal = $819,288

Grand Total All Awards = $3,277,152

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Drug Target Discovery, Validation, and Prioritization for Schistosomiasis

Award Number: R01AI167967

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: 12/20/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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