Ancillary POInT Research (RFP)
In 2023, GPPAD announced a Request For Proposal (RFP) for investigators to perform innovative research on biosamples from the GPPAD POInT clinical trial utilizing cutting-edge analysis techniques relevant to pancreatic, metabolic, or immune research. The projects selected for funding complement GPPAD’s ongoing research approaches and analyses.
Overview of funded projects:
Early life epigenomic signatures, primed immune states and the development of type 1 diabetes
Tomi Pastinen, University of Missouri-Kansas City School of Medicine, Children’s Mercy – Kansas City and Children’s Mercy Research Institute, USA
The project aims to identify key epigenomic switches that determine the overall activity state of the immune system that leads to the development of islet autoantibodies and subsequent type 1 diabetes, which could serve as early points of intervention. Novel analyses (snRNA, snATAC, vaccine response profiles) will enrich GPPAD with wide utility in identifying environmental triggers and genetic causes of type 1 diabetes.
ELICIT – Early onset type 1 diabetes prognostic TCR signature identification
Encarnita Mariotti-Ferrandiz, Sorbonne University, France
The general objective is to study blood CD4 T regulatory and CD8 T-cell TCR repertoires from islet autoantibody seropositive children verus seronegative ones, over the course of POInT intervention.
Precision profiling antigen specific T cells in POInT: Investigating the relationship between proinsulin specific CD4 T cells, pathogenic autoimmunity and viral infection
Timothy Tree, Department of Immunobiology, School of Immunology & Microbial Sciences, King’s College London, UK
The overarching aim is to test the hypothesis that in young individuals at high genetic risk of developing type 1 diabetes, tolerance to islet antigens is not simply the absence of a response but is characterized by an active state of immune tolerance to islet antigens and that this tolerance can be influenced by antigen specific immunotherapy and/or exposure to infection.
Early-onset autoimmunity and the exocrine pancreas
Kathleen Gillespie, Bristol Medical School, Southmead Hospital, UK
Longitudinal profiling of trypsinogen levels in children with an elevated genetic risk for type 1 diabetes comparing children who develop islet autoantibodies to those who do not, aiming to define a potential marker for risk and progression rate as well as clinical trial efficacy.
Identification of immune-metabolic changes associated with oral insulin treatment and type 1 diabetes onset
Margarita Dominguez-Villar, Department of Infectious Disease Immunology and Infection, Imperial College London, UK
Characterization of metabolically peripheral blood mononuclear cell populations and quantification of autoantigen-specific T cell frequency and functionality from the POInT trial participants over time.