Grant A. Challen, PhD

Grant A. Challen, PhD


Division of Oncology
Mail Stop 8007-0057-07
Washington University
660 South Euclid Avenue
St. Louis, MO 63110

Room 744 Southwest Tower (lab)

Research Interests
  • Hematopoietic stem cells
  • Leukemia stem cells
  • Epigenetic modifications

Research: 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
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



  • 2006-2002: PhD in Developmental Biology, The University of Queensland, Brisbane, QLD, Australia (Mentor: Professor Melissa Little)
  • 2000-1997: BSc(Hons) in Molecular Biology, Central Queensland University, Rockhampton, QLD, Australia

Post-Graduate Training

  • 2012-2006: Post-doctoral Fellow, Baylor College of Medicine, Houston, TX (Mentor: Professor Margaret Goodell)

Academic Positions

  • present-2018: Associate Professor, Department of Medicine, Washington University, St. Louis, MO
  • 2018-2012: Assistant Professor, Department of Medicine, Washington University, St. Louis, MO

University & Hospital Appointments & Committees

  • present-2019: Pediatric Hematology-Oncology Training Program T32 Steering Committee
  • present-2018: IACUC Commitee Member
  • 2019: BioSURF Program Reviewer
  • 2019, 2018, 2016, 2015: Siteman SIP Study Section
  • 2016: Washington University Leukemia Spore Scientific Review Committee
  • Siteman Cancer Center Member (Hematopoietic Development and Malignancy Program)
  • Institute of Clinical and Translation Sciences Member
  • DBBS Member (Developmental, Regenerative and Stem Cell Biology Program; Molecular Cell Biology Program; Molecular Genetics and Genomics Program; Computational and Systems Biology Program)

Honors & Awards

  • 2018: Leukemia and Lymphoma Scholar Award
  • 2015: V Foundation V Scholar Award
  • 2015: Sidney Kimmel Foundation Scholar Award
  • 2014: American Society of Hematology ASH Junior Faculty Scholar
  • 2013: Edward Mallinckrodt, Jr. Foundation Scholar
  • 2012: Alex’s Lemonade Stand “A” Award
  • 2011: Forbeck Scholar Award (William Guy Forbeck Research Foundation)
  • 2010: NIH K99/R00 Career Development Award
  • 2010: American Society of Hematology ASH Scholar Award
  • 2010: Dan L. Duncan Cancer Center Symposium “Best Oral Presentation”
  • 2010: American Society of Hematology Joanne Levy Memorial Medal

Editorial Responsibilities

  • 2020-2018: iScience (Cell Press), Editorial Board Member

National Service and Leadership Roles

  • 2022: NIH ZRG1 Fellowships Reviewer
  • 2022: Alex’s Lemonade Stand Foundation (ALSF) “A-award” Grant Reviewer
  • 2022-2021: Leukemia and Lymphoma Society Career Development Program Reviewer
  • 2021: NIH ZRG1 Special Emphasis Panel Reviewer
  • 2021: NCI ZCA1 RPRB-H PQ3 Study Section Reviewer
  • 2021: NIH BBHV Study Section Ad-hoc Reviewer
  • 2020: NIH 2021/01 ZRG1 VH-C (02) Vascular and Hematology Reviewer (Study Section Chair)
  • 2020: NIH CAMP Study Section Ad-hoc Reviewer
  • 2020: Kay Kendall Leukemia Fund (KKLF) Scientific Reviewer
  • 2020: NIH NIDDK CCEH P&F Project External Reviewer
  • 2020: NIH NIDDK RC2 Grant Reviewer
  • 2020: Alex’s Lemonade Stand Foundation (ALSF) “Crazy 8” Grant Reviewer
  • 2020: Leukemia and Lymphoma Society Career Development Program Grant Reviewer
  • 2020-2018: Kay Kendall Leukemia Fund (KKLF) Scientific Reviewer
  • 2019: Meeting Organizer Evans MDS Summit (St. Louis, MO; October 24-25)
  • 2019: Canada Research Chair (CRC) Program Reviewer
  • 2019: Istituto Pasteur Italia Scientific Reviewer
  • 2019: UK Bloodwise Project Grant Reviewer
  • 2019: Netherlands Organization for Health Research and Development Grant Reviewer
  • 2019, 2017: Edward P. Evans MDS Foundation Scientific Reviewer
  • 2018: Welcome Trust Scientific Reviewer
  • 2018: NIH Scientific Reviewer MCH Study Section (Ad Hoc)
  • 2018: Biotechnology and Biological Sciences Research Council (BBSRC) Scientific Reviewer
  • 2017: Swiss Cancer Foundation Scientific Reviewer
  • 2017: NIH Scientific Reviewer TAG Study Section (Ad Hoc)
  • 2016: Connecticut Regenerative Medicine Research Fund (RMRF) Reviewer

Professional Societies & Organizations

  • present-2012: Society for Hematology and Stem Cells (ISEH)
    • present-2017: Publications committee
      • present-2019: Chair
    • 2016-2014: Head of Webinars Subcommittee
    • 2016-2012: ISEH New Investigator Committee
  • present-2009: American Society of Hematology (ASH)
    • 2018: ASH-a-Palooza Blood Drop Speaker
    • 2018-2014: ASH Ad Hoc Scientific Committee on Epigenetics and Genomics
      • 2017: Chair
      • 2016: Vice-chair
    • 2015-2014: Abstract Review Committee, Hematopoietic Stem and Progenitor Cell Biology
      • 2015: Chair
  • present-2005: International Society For Stem Cell Research (ISSCR)
    • 2020, 2019: Abstract Reviewer