Jonathan Steinman, MD, PhD

Alexander M. White, III Postdoctoral Research Fellowship Award
$25,000 over one year

Columbia University

Spatial transcriptomics of biopsies from children reveals dysregulated metabolic responses and zonal redistribution of inflammation driving the unique distribution of disease in pediatric MASH

Mentor: Utpal Pajvani, MD, PhD

Diseases caused by obesity are becoming ever more common in children and it is now becoming clear that they do not have the same clinical course as diseases of the same name in adults. For instance, obesity-driven accumulation of fat and inflammation in the liver (called metabolic dysfunction-associated steatohepatitis, MASH) has two different disease subtypes at the microscopic level: one that occurs in the ‘central’ part of the liver’s microscopic structure (MASH-central/MASH-c), and another that occurs at the other end of the microscopic structure, the ‘portal’ area (MASH-portal/MASH-p). MASH-p is unique to children while MASH-c can occur in both adults and children, and there is evidence that children with MASH-p have worse metabolic health and worse liver health than those with MASH-c. This raises the possibility that MASH-p and MASH-c are two distinct diseases with different underlying causes. Our research focuses on understanding how the different types of MASH develop, using a cutting-edge type of analysis that can identify the abundance and microscopic location of all genes within the liver. Our results will help explain how the unique children’s form of obesity-driven liver disease develops and may help to identify improved approaches for diagnosis or treatment of this unique and increasingly common disease.