About the Lab

The urea cycle functions in the liver to protect the brain from the toxic effects of ammonia, a breakdown product of dietary and cellular proteins. Six urea cycle enzymes and two mitochondrial transporters collectively convert ammonia into urea, which is excreted through the kidneys. Genetic defects in any of the urea cycle enzymes or transporters lead to accumulation of ammonia in the blood — called hyperammonemia — which can irreversibly damage the brain and could be lethal if left untreated. Current treatments for hyperammonemia focus on minimizing accumulation of ammonia through low-protein diet and activation of alternative pathways for ammonia disposal, but none of the treatments focus on protecting the brain from ammonia toxicity. Research in the Caldovic Laboratory focuses on developing new treatments for hyperammonemia and identifying blood biomarkers of brain injury from hyperammonemia.