Precision Medicine Models for Rare and Undiagnosed Diseases
In the BCM Center for Precision Medicine Models, we develop animal and cellular models to help end the diagnostic odyssey for individuals with rare and undiagnosed diseases. These models also serve as platforms for investigating potential therapeutic approaches. The Center’s work encompasses a broad spectrum of phenotypes, including skeletal, neurologic, cardiovascular, metabolic disorders, and congenital anomalies. Our findings inform clinical diagnostics, guide genetic counseling, and support the development of targeted therapies for these rare disorders.
Lysinuric Protein Intolerance as a Model for a Variety of Common Diseases
Lysinuric protein intolerance is an inherited disorder of amino acid transport associated with early-onset osteoporosis, short stature, lung disease, early-onset autoimmunity, renal involvement, and secondary urea cycle dysfunction. We have generated mouse models that recapitulate key features of the human disease, and we are using these models, along with complementary cell-based systems, to investigate the mechanisms underlying these diverse phenotypes. Our long-term goal is to leverage lysinuric protein intolerance as a model to better understand the role of cationic amino acid transport in fundamental biological processes, including growth, immune function, and bone development.
Investigating Long-Term Complications of 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. Our work will improve understanding of the natural history of liver disease in urea cycle disorders, an increasingly important area given the growing number of liver-directed therapies for these conditions.