NIH grant: Efficacy of targeting GAPM3 to block acute and chronic Toxoplasma gondii infections (1R01AI198553-01)

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NIH grant 1R01AI198553-01: Efficacy of targeting GAPM3 to block acute and chronic Toxoplasma gondii infections
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Kevin Michael Brown. Award: $463290.
Start: 2026-06-24T00:00:00.
PROJECT SUMMARY
 Toxoplasma gondii infects an estimated 25–30% of the human population and poses a major public
health challenge, particularly in immunocompromised individuals and during pregnancy. Current treatments are
limited by toxicity, incomplete efficacy, and an inability to eliminate chronic tissue cysts. There is a critical need
for new therapeutics that target proteins essential to both acute (tachyzoite) and chronic (bradyzoite) life stages.
Our research focuses on GAPM3, a structural membrane protein conserved across apicomplexans. Through in
vitro studies, we found that GAPM3 is essential for tachyzoite replication and structural integrity—its loss leads
to gliding motility defects, cellular collapse, and failure to complete the lytic cycle. Proteomic analysis revealed
interactions between GAPM3 and key components of the cytoskeleton and motility machinery. In vivo single-cell
RNA sequencing demonstrated that GAPM3 is also expressed in bradyzoites, suggesting its potential as a target
across both clinically relevant stages. Building on these findings, this proposal aims to (1) evaluate the
therapeutic efficacy of targeting GAPM3 in both acute and chronic infection models, (2) define the essential
structural and regulatory domains of GAPM3, and (3) advance precision drug development strategies that exploit
its unique and indispensable role in parasite biology. This work addresses a major unmet need by advancing a
promising, parasite-specific target for the treatment and possible eradication of toxoplasmosis.

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