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Elucidating how bacterial sphingolipids shape intestinal T cell responses during early life

Award Number: F31HD123788
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2027
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Elucidating how bacterial sphingolipids shape intestinal T cell responses during early life - Project Summary Preterm birth (birth before 37 week of gestation) affects ~10% of births worldwide and remains the leading cause of mortality in children under 5 years. In North America, nearly 1 in 6 preterm infants develops invasive infection in the early postnatal period, contributing to both acute mortality and long-term morbidity from organ damage. Despite substantial healthcare expenditure (>$17 billion annually in the US), infection remains a dominant threat. The preterm immune system exhibits impaired effector T cell function, which compromises pathogen defense. The gut microbiome, which is a critical driver of immune development in early life, is often dysbiotic in preterm infants, but the role of the perturbed gut microbiome in shaping preterm infant intestinal immunity remains undefined. This knowledge gap represents a major barrier to developing targeted interventions that enhance immune maturation in preterm infants. We have found that preterm infants have reduced levels of sphingolipid producing bacteria in their gut microbiomes and altered stool sphingolipid profiles compared to term infants. How bacterial sphingolipids modulate T cell responses in early life remains undefined. The objective of this F31 proposal is to elucidate how bacterial sphingolipids regulate gut T cell immunity during early life that is critical to protect infants against gut pathogens. We hypothesize that bacterial sphingolipids promote effector T cell responses that provide protection to gut pathobionts and pathogens during early life. In specific aim 1, we will assess T cell responses induced by the preterm and gut microbiome by colonizing neonatal germ-free mice with stool pooled from preterm or full-term infants (available in the Zeng lab). I will also determine how bacterial sphingolipids in outer membrane vesicles modulate responses to specific gut commensal microbes and pathogens. In aim 2, I will elucidate how bacterial sphingolipids modulate human T cell responses by interrogating how bacterial sphingolipids shape T cell metabolism. Our findings will inform the development of bacterial sphingolipid- based therapeutics to reduce infection risk in preterm infants, which would ultimately reduce severe gut infections in infants and improve their long-term health. We have assembled a multidisciplinary scientific committee consisting of my sponsor Dr. Zeng, co-sponsor Dr. Sonnenberg, and mentors Drs. Martin, Worgall, Lyden, Ehrt, and Inohara. This team will provide scientific input and mentorship to support the successful completion of the proposed project and training plan. My mentors provide research and clinical expertise in immunology, neonatology, sphingolipid biology, extracellular vesicle biology, microbiology, and computational biology. This team, along with the strong training environment offered by the Tri-Institute consisting of Weill Cornell, Memorial Sloan Kettering and Rockefeller University will enable me to obtain the skills and background necessary to become an independent investigator conducting research on the early life gut microbiome with the goal of improving neonatal health.


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	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Child Health and Human Development Extramural Research	000	1	8/18/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Elucidating how bacterial sphingolipids shape intestinal T cell responses during early life

Award Number: F31HD123788

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2027

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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