Tomi Pastinen, MD, PhD
Dee Lyons/Missouri Endowed Chair in Pediatric Genomic Medicine; Director, Center for Pediatric Genomic Medicine; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Professor of Cancer Biology, University of Kansas School of Medicine
Full BiographyElin Grundberg, PhD
Roberta D. Harding & William F. Bradley Jr. Endowed Chair in Genomic Research; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Associate Professor of Pathology, University of Kansas School of Medicine
Full BiographyTodd Bradley, PhD
Director, Immunogenomics, Genomic Medicine Center; Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Pediatrics, University of Kansas School of Medicine
Full Biography
Tomi Pastinen, MD, PhD, Elin Grundberg, PhD, and Todd Bradley, PhD, Genomic Medicine Center, received a two-year, $550,000 award from the Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) for their project, “Early life epigenomic signatures, primed immune states and the development of Type 1 diabetes.”
Type 1 diabetes (T1D) is an autoimmune disease that develops when the immune system becomes dysregulated and attacks healthy pancreatic islet cells. This leads to chronic inflammation, tissue damage, and the loss of the ability to produce insulin. Islet inflammation is characterized by innate and adaptive immune processes that are proinflammatory. Some of the factors that influence immune state activation include genetic make-up, responses to pathogens, and environmental exposures. However, much remains unknown about early molecular determinants of T1D that might predict diagnosis.
“Our goal is to identify key epigenomic switches that determine the activity state of the immune system which lead to the development of type 1 diabetes. Identifying those switches could lead to early intervention,” said Dr. Grundberg.
In preliminary studies, Dr. Pastinen identified a cellular immune state that stratified at-risk children for T1D before immunological biomarkers of islet autoantibodies (IAA) were present. Building on those findings, this study’s objective is to test the hypothesis that children who have detectable IAA and are subsequently diagnosed with T1D have a primed immune system imprinted early in life. This primed immune state will be reflected by monocyte-specific molecular signatures representing increased proinflammatory activity together with increased vaccine antibody responses.
The study has two aims:
- Aim 1: Determine circulating immune cell populations and molecular pathways that contribute to primed immune cell states and subsequent development of T1D using single-nuclei multiomics.
- Aim 2: Identify antibody and cytokine serological determinants of primed or tolerant immune states that could predict T1D development.
“This work is significant because it will define the molecular and cellular features of early-life immune states and determine if these immune states could predict type 1 diabetes in later life,” said Dr. Bradley.