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Enterovirus-reactive placental T cells as risk predictors of pancreatic islet autoimmunity

Award Number: K99HD122006
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Enterovirus-reactive placental T cells as risk predictors of pancreatic islet autoimmunity - Project Summary CANDIDATE: The candidate is a postdoctoral fellow in the Yale Department of Pediatrics with over ten years of immunology training in host-microbe interactions. He is dedicated to an academic research career that seeks to define the environmental determinants of childhood autoimmune disease in early-life immune cells, with the long- term goal of becoming an independent principal investigator. His publication record and successful competition for postdoctoral fellowship awards demonstrate his capabilities as he nears a transition to independence. RESEARCH: Type 1 diabetes (T1D) costs an estimated $10B in healthcare every year and is increasing in prevalence among children in the United States. This increasing prevalence is concerning and points to environmental factors in the etiology of T1D and in other autoimmune diseases. Exposure to enteroviruses in early life is epidemiologically associated with increased T1D risk later in childhood, but the field lacks a mechanistic basis for early immunopathology. However, existing treatments fail to address the root cause of the disease: loss of tolerance for self-antigen by specific pathogenic T cell clones. Due to the need for studies that integrate environmental triggers and immune responses at the molecular level, the overarching goal of this proposal is to evaluate placental T cell reactivity to viral antigens and pancreatic islet autoantigens as risk factors for the development of pancreatic islet autoimmunity. Central hypothesis: placental T cell reactivity to enterovirus antigens is positively correlated with reactivity to islet autoantigens. To test this hypothesis, this project will define molecular signatures of prenatal enterovirus exposures using T cell receptor (TCR) repertoire sequencing (Aim1, K99), identify TCR clones that are reactive to viral antigens and/or autoantigens using an innovative high throughput approach (Aim 2, K99), and classify features of early life T cell clones that contribute to later islet autoantibody development using computational modeling (Aim 3, R00). ENVIRONMENT: The candidate will be mentored by experts in human immunology and longitudinal computational modeling during the mentored phase of the award (Liza Konnikova, MD PhD & John Tsang, PhD), and is engaging in advanced research training and career development activities preparing him for an independent faculty career. He is nearly prepared to seek and secure a faculty appointment and launch a research program that focuses on early-life immune responses to microbes and antigenic determinants of healthy versus dysregulated immune development in children. The innovative studies proposed for the award period will clear a path for the candidate toward independence and create new opportunities in the prediction of diabetes risk and the development of preventive treatments.


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 = $130,923 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Child Health and Human Development Extramural Research	000	1	7/3/2026	NEW	$130,923
														Subtotal = $130,923

Grand Total All Awards = $130,923

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Enterovirus-reactive placental T cells as risk predictors of pancreatic islet autoimmunity

Award Number: K99HD122006

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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