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We have an active research effort that is investigating genetic mutations in severe diarrheal diseases and congenital enteropathies. Once a mutation is identified, we can investigate how it causes disease and seek ways to counteract its effects. Because these conditions are so rare, we collaborate with the multicenter Pediatric Congenital Diarrhea and Enteropathy(PediCODE) Consortium.

To date, 20 to 25 genes have been identified that cause different types of congenital diarrhea and enteropathy. As we add to this list, we will be able provide families with a precise, rapid diagnosis and better, customized treatments. We welcome families interested in participating in research (email: enteropathy@childrens.harvard.edu).

Current studies include:

  • DNA sequencing. We offer families the opportunity to have their child’s DNA sequenced with advanced, next-generation techniques. Recently, for example, we identified a recessive mutation in the WNT2B gene in three newborns with severe diarrhea from two unrelated families.
  • Cellular studies. Once we identify a mutation, we can investigate its effects in the laboratory in a number of ways. For example, we can recreate a patient’s intestinal cells in a dish, carrying the causative mutation, or even create a three-dimensional “mini intestine” that models the disease in miniature. Advances in stem-cell and gene editing technologies have helped to facilitate this work.
  • Drug discovery. Our cell and “mini intestine” models of congenital enteropathy are allowing us to rapidly test whole batteries of drugs to see if they can reverse the effects of the disease. Many of the drugs we are screening have already been approved for use by the Food and Drug Administration (FDA), so any that prove to be effective could become available more rapidly than a completely new drug. Examples of this work include:
    • Microvillus inclusion disease. In MVID, the cells that line the intestine cannot properly absorb fluid and nutrients. Dr. Jay Thiagarajah and his team have been studying these cells and will soon test a battery of FDA-approved drugs to see if they improve the cells’ function.
    • Severe enteropathy caused by TTC7A mutations. We are modeling this genetic defect in intestinal cells and are testing some FDA-approved drugs that may reverse some of the defects in cell function.
    • Congenital sodium diarrhea caused by GUCY2 mutations. We are testing a battery of anti-secretory anti-diarrheal compounds on patient derived cells to see if they can reduce fluid losses in this disorder.