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Ebert Lab Research


Genetics, biology, and treatment of myeloid malignancies


A major focus of the Ebert laboratory is to understand the molecular basis of blood cancers. We investigate the mutations that drive the initiation and progression of myeloid malignancies, and the factors that predict outcome and response to therapy. We characterized clonal hematopoiesis of indeterminate potential (CHIP) and discovered that CHIP, while pre-malignant, increases the risk of not only myeloid malignancies, but also cardiovascular disease and other inflammatory diseases. Our genetic studies have identified somatic mutations in myelodysplastic syndrome (MDS) that predict overall survival and outcome following bone marrow transplantation.  We have generated and characterized a range of models of CHIP and MDS, including the use of CRISPR/Cas9 genome editing of hematopoietic stem and progenitor cells.  

Our investigation into the mechanism of action of lenalidomide, a drug with efficacy in hematologic malignancies, particularly MDS and multiple myeloma, revealed that lenalidomide and related compounds act by modulating the function of an E3 ubiquitin ligase, resulting in the highly specific degradation of disease-related proteins.  We have subsequently explored a broader range of protein substrates that can be degraded by lenalidomide and other thalidomide derivatives, and we have elucidated other novel mechanisms of drug-induced protein degradation.  For example, we have characterized a mechanism of drug-induced polymerization of BCL6, a lymphoma oncogene, that results in highly specific ubiquitination and degradation the protein.

Main Research Themes


Clonal Hematopoiesis of Indeterminate Potential

​Clonal Hematopoiesis and Hematologic Malignancies

​Discovering the genetic mutations that drive clonal hematopoiesis and myeloid malignancies, exploring the biological basis of transformation, and piecing together how these contribute to malignant and non-malignant diseases.
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Targeted Protein Degradation

Identifying genes and proteins involved in protein degradation, dissecting mechanisms of action for novel protein degraders, and finding therapeutic applications for promising candidate degraders.
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©2024 Ebert Lab at Dana-Farber Cancer Institute
  • HOME
  • Research
    • Clonal Hematopoiesis and Hematologic Malignancies
    • Targeted Protein Degradation
  • PEOPLE
    • Principal Investigator
    • Current Lab Members
    • Lab Alumni
    • Photo Gallery
  • PUBLICATIONS
  • SUPPORT
  • CONTACT