Center for Pediatric Genomics
Using Human iPSC-Derived Beta Cells to Identify Novel Genes Causing CHI

Using Human iPSC-Derived Beta Cells to Identify Novel Genes Causing CHI

Principle Investigator: Jim Wells, PhD, Division of Developmental Biology, Mansa Krishnamurthy, MD, MSc, Division of Endocrinology

A photo of Jim Wells.Congenital hyperinsulinism results in the pancreas either producing or releasing too much insulin which can cause excess fetal weight gain and blood glucose levels to be dangerously low. We are identifying the genetic and molecular underpinnings of congenital hyperinsulinism (CHI). CHI is a heterogenous group of disorders, causing an overproduction of insulin, most frequently causing persistent hypoglycemia in infants and children. Hyperinsulinism results in somatic overgrowth at birth causing traumatic birth defects, as well as hypoglycemia in infancy and childhood causing neurocognitive impairment. Currently, there are approximately 15 known monogenic forms of CHI, as well as several other syndromic forms. There remains 50% of patients with CHI without an identified genetic diagnosis, suggesting that there are genetic loci that remain yet to be discovered. We are working to identify novel genes that cause CHI in patients with an unknown genetic etiology by using whole exome sequencing. Once identified, we generate induced pluripotent stem cell lines from these patients and differentiate them into pancreatic β cells. Using genome editing, we correct the genetic defect and elucidate the underlying molecular mechanisms that cause CHI in these patients.

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