Despite advances in the treatment of leukemia, there are populations of patients who still have a poor prognosis, or who relapse and become resistance to standard frontline therapies. A major focus of the Kelliher lab is to understand the underlying mechanisms that contribute to refractory T cell acute lymphoblastic leukemia (T-ALL). For this purpose, they utilize the mouse as a model system to understand the genetic and epigenetic basis of therapeutic resistance in T-ALL. In particular, they rely on genetically engineered mouse models where it is possible to analyze patient-derived xenografts from pediatric and adult T-ALL patients at diagnosis and upon relapse.