Oncology Division
Alphabetical list (active faculty):   
Grant A. Challen

Grant A. Challen, PhD

Associate Professor

Department of Medicine

Oncology Division

Stem Cell Biology

Research Interests

  • Hematopoietic stem cells
  • Leukemia stem cells
  • Epigenetic modifications


  • 314-362-0987 (office)
  • 314-362-1953 (fax)
  • Division of Oncology
    Mail Stop 8007-0057-07
    Washington University
    660 South Euclid Avenue
    St. Louis, MO 63110
  • Room 744 Southwest Tower (lab)


Hematopoietic stem cells (HSCs) reside in the bone marrow and are defined by their capacity for lifetime maintenance of the blood and bone marrow, achieved through their differentiation into the myriad cellular components, as well as their ability to generate additional stem cells via self-renewal. The mechanisms that instruct the fate of stem cells toward differentiation versus self-renewal are still relatively poorly understood. A number of transcription factors have been identified as critical for HSC maintenance and self-renewal; however, we have little insight into how these factors are orchestrated by epigenetic mechanisms to ensure blood homeostasis. The central theme of my research is understanding how epigenetic marks such as histone methylation and acetylation, DNA methylation, and 5-hydroxymethylation coordinately act to regulate normal HSC function and how these processes go awry in hematopoietic diseases such as leukemia and lymphoma. We also use various mouse genetic models to study the roles of genetic mutations of different components of the epigenetic machinery in cancers of the blood and bone marrow.

Ongoing projects in the lab include

  • The role of DNA methylation in hematopoietic stem cell fate decision
  • The functions of epigenetic mutations in leukemias and lymphomas
  • Modifying the epigenome for somatic cell reprogramming

HSC genes

Model for Dnmt3a action in HSCs. "HSC genes" are mostly unmethylated and expressed in normal HSCs (left). Upon receiving a signal to differentiate, Dnmt3a methylates and silences these regions to permit lineage commitment. This is associated with a loss of H3K4me3. These genes are then repressed in B-cells. Dnmt3a-KO HSCs (right) cannot silence these "HSC genes" so upon receiving a stimulus to differentiate, these genes remain expressed due to lack of methylation and elevated H3K4me3. Upon cell division, the HSC self-renewal pathway remains the default state for Dnmt3a-KO HSCs resulting in their accumulation in the bone marrow. Of the few Dnmt3a-KO HSCs that do differentiate, their progeny show incomplete methylation and repression of "HSC genes." Nat Genet 2011 Dec 4;44(1):23-31

Parsing out blood stem cells