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The Role of Hookworm Glycoproteins in Parasite Biology and Disease Pathogenesis

Award Number: F31AI197571
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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The Role of Hookworm Glycoproteins in Parasite Biology and Disease Pathogenesis - Abstract Hookworms are parasitic worms (helminths) that attach to the intestinal mucosa, where they ingest host blood from lacerated blood vessels, leading to severe anemia and growth delay. Elucidating mechanisms of hookworm pathogenesis is critical to the development of novel interventions that can be used to combat these and related helminthiases. Molecular interactions at the host-parasite interface are driven by the release of excretory/secretory proteins (ES) by adult hookworms in the small intestine. Previous studies conducted in our lab have demonstrated robust serum IgG and mucosal IgA responses to hookworm ES post-infection. Intriguingly, literature from related helminth systems has reported roles for antigen glycosylation in mediating host antibody responses to infection. However, specific glycan moieties on hookworm ES proteins have yet to be identified, and their roles in immunopathogenesis remain unstudied. We compiled a library of nematode glycan structures and developed a glycoproteomic workflow that identified 83 glycoproteins (326 glycopeptides) in the larvae of the human hookworm Ancylostoma ceylanicum. Thirty-eight of these glycopeptides were modified with phosphorylcholine, a known immunogenic glycan substitution, suggesting a role for protein glycosylation in hookworm pathogenesis. This research will leverage advances in glycobiology to identify glycosylated hookworm antigens and interrogate their roles in hookworm immunopathogenesis. First, we will characterize the glycoproteins present throughout development in two species of human hookworm and define the glycan structures present in each. Next, we will generate native glycan microarrays from hookworm proteins and probe them with serum and mucosal reagents using a permissive animal model. Finally, we propose experiments to identify ES glycoproteins recognized by host IgG and mucosal IgA and investigate their role in mediating resistance to infection. This research will provide novel insight into glycosylation-mediated mechanisms underlying hookworm immunopathogenesis, ultimately leading to future work aimed at developing novel vaccines, drugs, and diagnostics to combat this globally important parasite. The combined expertise of the sponsor and a team of internal/external collaborators constitute a robust training environment that will support development as an independent scientist committed to advancing research in parasitic diseases.


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 = $50,114 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	000	1	4/9/2026	NEW	$50,114
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Allergy and Infectious Diseases Research	001	1	4/9/2026	NEW	$0
														Subtotal = $50,114

Grand Total All Awards = $50,114

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The Role of Hookworm Glycoproteins in Parasite Biology and Disease Pathogenesis

Award Number: F31AI197571

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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