Grant A. Challen, PhD

Professor

Phone: 314-362-0987
Fax: 314-362-1953
Email: grantchallen@nospam.wustl.edu

Address:
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

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

Challen Lab

Profiles (publications)

Biosketch

Education

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