Jack Uetrecht

After many unsuccessful attempts to develop animal models, Uetrecht’s team discovered that blocking immune tolerance unmasked the ability of drugs to cause idiosyncratic reactions in animals and leads to idiosyncratic reactions very similar to those in humans. This was accomplished with immune checkpoint inhibitors, which were developed to treat cancer by enabling a patient’s immune system to attack and destroy cancers. These animal models are allowing the team to perform mechanistic studies that were previously impossible. The team also uses in vitro studies to study exactly how drugs initiate an immune response. Another focus is on metabolism in the skin. Although most drug metabolism occurs in the liver, the team discovered that some drugs can form reactive metabolites mediated by sulfotransferase, which is present at high concentrations in the skin. It is only with a better mechanistic understanding that we will be able to prevent severe idiosyncratic drug reactions.

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