Research Abstract
The primary focus of the Ebert laboratory is the biology and treatment of clonal hematopoiesis and myeloid malignancies. Our genetic studies have led to the characterization of clonal hematopoiesis of indeterminate potential (CHIP) and the identification of mutations in MDS that predict overall survival, outcome following bone marrow transplantation, and response to hypomethylating agents. We use functional screens to identify therapeutic targets and probe disease biology, and we develop novel models of hematologic malignancies to validate candidate therapies. Studies of the mechanism of action of lenalidomide, a drug with efficacy in MDS, revealed that lenalidomide and related compounds act by modulating the function of an E3 ubiquitin ligase, resulting in the drug-induced degradation of key therapeutic targets in hematologic malignancies.