Liver Disease in Urea Cycle Disorders
Urea cycle disorders are one of the most common inborn errors of liver metabolism. With early diagnosis and improved therapies targeting elevated ammonia levels in the blood, long-term survival of patients with these diagnoses is improving. However, long-term complications, such as chronic liver disease, are becoming more apparent. In collaboration with the Urea Cycle Disorders Consortium of the NIH Rare Diseases Clinical Research Network, we are performing a series of clinical studies investigating new tools for monitoring liver disease in urea cycle disorders. To complement our clinical work, we are performing translational studies in the laboratory investigating the underlying mechanisms of liver disease in mouse models and cell models of the disorders.
Our long-term goal is to provide better screening strategies for liver disease and possibly develop new therapeutic strategies targeting this complication in individuals with urea cycle disorders. In addition, we expect those insights gained from our studies of liver disease in the setting of urea cycle dysfunction will be applicable to more common liver diseases in humans.
Lysinuric Protein Intolerance as a Model for a Variety of Common Diseases
Lysinuric protein intolerance is an inborn error of amino acid transport that is associated with early-onset osteoporosis, short stature, lung disease, early-onset autoimmunity, renal disease, and secondary urea cycle dysfunction. We have generated a Slc7a7 knockout mouse that mimics the human phenotype, and we utilize this mouse model as well as cell models to explore the mechanisms underlying the various phenotypes associated with this disorder. Our long-term goal is to use Lysinuric Protein Intolerance as a model to provide insights into the role of the transport of cationic amino acids in basic processes such as growth, immunity, and bone development.
Investigating the Underlying Genetic Basis of Rare Pediatric Genetic Diseases
Our laboratory is also involved in a variety of gene discovery projects focusing on rare disorders in the Undiagnosed Diseases Network. In addition, Dr. Burrage is the Director of the Clinical Translational Core within the BCM Center for Precision Medicine Models. In this role, we work with other members of the Center to optimize precision animal models for rare diseases and to translate findings from these models back to clinicians for integration into clinical diagnostics, clinical care, and clinical trials.