Faculty
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

Contact

  • 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)

Peer-reviewed Publications

  • The Simplified MPP Isolation Scheme: Establishing a Consensus Approach for Multipotent Progenitor Identification
    Challen GA, Pietras EM, Wallscheid NC, Signer RAJ
    Exp Hematol 2021 Oct 11; [Epub ahead of print]
  • Pevonedistat Targets Malignant Cells in Myeloproliferative Neoplasms in Vitro and in Vivo Via NFkB Pathway Inhibition
    Kong T, Brunelli Albertoni Laranjeira A, Collins T, De Togni ES, Wong AJ, Fulbright MC, Ruzinova M, Celik H, Challen G, Fisher DAC, Oh ST
    Blood Adv 2021 Oct 13; [Epub ahead of print]
  • TET2 and DNMT3A Mutations Exert Divergent Effects on DNA Repair and Sensitivity of Leukemia Cells to PARP Inhibitors
    Maifrede S, Le BV, Nieborowska-Skorska M, Golovine K, Sullivan-Reed K, Dunuwille WMB, Nacson J, Hulse M, Keith K, Madzo J, Caruso LB, Gazze Z, Lian Z, Padella A, Chitrala KN, Bartholdy BA, Matlawska-Wasowska K, Di Marcantonio D, Simonetti G, Greiner G, Sykes SM, Valent P, Paietta EM, Tallman MS, Fernandez HF, Litzow MR, Minden MD, Huang J, Martinelli G, Vassiliou GS, Tempera I, Piwocka K, Johnson N, Challen GA, Skorski T
    Cancer Res 2021 Oct 1;81(19):5089-5101
  • Chronic Infection Drives Dnmt3a-Loss-Of-Function Clonal Hematopoiesis Via IFNgamma Signaling
    Hormaechea-Agulla D, Matatall KA, Le DT, Kain B, Long X, Kus P, Jaksik R, Challen GA, Kimmel M, King KY
    Cell Stem Cell 2021 Aug 5;28(8):1428-1442
  • A Humanized Animal Model Predicts Clonal Evolution and Therapeutic Vulnerabilities in Myeloproliferative Neoplasms
    Celik H, Krug E, Zhang CR, Han W, Issa N, Koh WK, Bjeije H, Kukhar O, Allen M, Li T, Fisher DA, Fowles JS, Wong TN, Stubbs MC, Koblish HK, Oh ST, Challen GA
    Cancer Discov 2021 Jun 30; [Epub ahead of print]
  • Epigenomic Regulation of Human T-Cell Leukemia Virus by Chromatin-Insulator CTCF
    Cheng X, Joseph A, Castro V, Chen-Liaw A, Skidmore Z, Ueno T, Fujisawa JI, Rauch DA, Challen GA, Martinez MP, Green P, Griffith M, Payton JE, Edwards JR, Ratner L
    PLoS Pathog 2021 May 21;17(5):e1009577
  • LKB1/STK11 Is a Tumor Suppressor in the Progression of Myeloproliferative Neoplasms
    Marinaccio C, Suraneni P, Celik H, Volk A, Wen QJ, Ling T, Bulic M, Lasho T, Koche RP, Famulare CA, Farnoud N, Stein B, Schieber M, Gurbuxani S, Root DE, Younger ST, Hoffman R, Gangat N, Ntziachristos P, Chandel NS, Levine RL, Rampal RK, Challen GA, Tefferi A, Crispino JD
    Cancer Discov 2021 Jun;11(6):1398-1410
  • Interferon Regulatory Factor 4 as a Therapeutic Target in Adult T-Cell Leukemia Lymphoma
    Rauch DA, Olson SL, Harding JC, Sundaramoorthi H, Kim Y, Zhou T, MacLeod AR, Challen G, Ratner L
    Retrovirology 2020 Aug 28;17(1):27
  • TGFbetaR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment
    Le BV, Podszywalow-Bartnicka P, Maifrede S, Sullivan-Reed K, Nieborowska-Skorska M, Golovine K, Yao JC, Nejati R, Cai KQ, Caruso LB, Swatler J, Dabrowski M, Lian Z, Valent P, Paietta EM, Levine RL, Fernandez HF, Tallman MS, Litzow MR, Huang J, Challen GA, Link D, Tempera I, Wasik MA, Piwocka K, Skorski T
    Cell Rep 2020 Oct 6;33(1):108221
  • Radiation Induces Iatrogenic Immunosuppression by Indirectly Affecting Hematopoiesis in Bone Marrow
    Kapoor V, Collins A, Griffith K, Ghosh S, Wong N, Wang X, Challen GA, Krambs J, Link D, Hallahan DE, Thotala D
    Oncotarget 2020 May 12;11(19):1681-1690
  • Divergent Effects of Dnmt3a and Tet2 Mutations on Hematopoietic Progenitor Cell Fitness
    Ostrander EL, Kramer AC, Mallaney C, Celik H, Koh WK, Fairchild J, Haussler E, Zhang CRC, Challen GA
    Stem Cell Reports 2020 Apr 14;14(4):551-560
  • Inflammatory Cytokines Promote Clonal Hematopoiesis With Specific Mutations in Ulcerative Colitis Patients
    Zhang CRC, Nix D, Gregory M, Ciorba MA, Ostrander EL, Newberry RD, Spencer DH, Challen GA
    Exp Hematol 2019 Dec;80:36-41e3
  • IRAK4 Mediates Colitis-Induced Tumorigenesis and Chemoresistance in Colorectal Cancer
    Li Q, Chen Y, Zhang D, Grossman J, Li L, Khurana N, Jiang H, Grierson PM, Herndon J, DeNardo DG, Challen GA, Liu J, Ruzinova MB, Fields RC, Lim KH
    JCI Insight 2019 Oct 3;4(19)
  • Kdm6b Regulates Context-Dependent Hematopoietic Stem Cell Self-Renewal and Leukemogenesis
    Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA
    Leukemia 2019 Oct;33(10):2506-2521
  • JARID2 Functions as a Tumor Suppressor in Myeloid Neoplasms by Repressing Self-Renewal in Hematopoietic Progenitor Cells
    Celik H, Koh WK, Kramer AC, Ostrander EL, Mallaney C, Fisher DAC, Xiang J, Wilson WC, Martens A, Kothari A, Fishberger G, Tycksen E, Karpova D, Duncavage EJ, Lee Y, Oh ST, Challen GA
    Cancer Cell 2018 Nov 12;34(5):741-756e8
  • Loss of Dnmt3a Immortalizes Hematopoietic Stem Cells in Vivo
    Jeong M, Park HJ, Celik H, Ostrander EL, Reyes JM, Guzman A, Rodriguez B, Lei Y, Lee Y, Ding L, Guryanova OA, Li W, Goodell MA, Challen GA
    Cell Rep 2018 Apr 3;23(1):1-10
  • Breast and Pancreatic Cancer Interrupt IRF8-Dependent Dendritic Cell Development to Overcome Immune Surveillance
    Meyer MA, Baer JM, Knolhoff BL, Nywening TM, Panni RZ, Su X, Weilbaecher KN, Hawkins WG, Ma C, Fields RC, Linehan DC, Challen GA, Faccio R, Aft RL, DeNardo DG
    Nat Commun 2018 Mar 28;9(1):1250
  • An Activating Mutation of Interferon Regulatory Factor 4 (IRF4) in Adult T-Cell Leukemia
    Cherian MA, Olson S, Sundaramoorthi H, Cates K, Cheng X, Harding J, Martens A, Challen GA, Tyagi M, Ratner L, Rauch D
    J Biol Chem 2018 May 4;293(18):6844-6858
  • A TFIID-SAGA Perturbation That Targets MYB and Suppresses Acute Myeloid Leukemia
    Xu Y, Milazzo JP, Somerville TDD, Tarumoto Y, Huang YH, Ostrander EL, Wilkinson JE, Challen GA, Vakoc CR
    Cancer Cell 2018 Jan 8;33(1):13-28e8
  • The GNAS(R201C) Mutation Associated With Clonal Hematopoiesis Supports Transplantable Hematopoietic Stem Cell Activity
    Ostrander EL, Koh WK, Mallaney C, Kramer AC, Wilson WC, Zhang B, Challen GA
    Exp Hematol 2018 Jan;57:14-20
  • Protein Kinase C Epsilon Is a Key Regulator of Mitochondrial Redox Homeostasis in Acute Myeloid Leukemia
    Di Marcantonio D, Martinez E, Sidoli S, Vadaketh J, Nieborowska-Skorska M, Gupta A, Meadows JM, Ferraro F, Masselli E, Challen GA, Milsom MD, Scholl C, Frohling S, Balachandran S, Skorski T, Garcia BA, Mirandola P, Gobbi G, Garzon R, Vitale M, Sykes SM
    Clin Cancer Res 2018 Feb 1;24(3):608-618
  • Dnmt3a Regulates T-Cell Development and Suppresses T-ALL Transformation
    Kramer AC, Kothari A, Wilson WC, Celik H, Nikitas J, Mallaney C, Ostrander EL, Eultgen E, Martens A, Valentine MC, Young AL, Druley TE, Figueroa ME, Zhang B, Challen GA
    Leukemia 2017 Nov;31(11):2479-2490
  • Clonal Haematopoiesis Harbouring AML-Associated Mutations Is Ubiquitous in Healthy Adults
    Young AL, Challen GA, Birmann BM, Druley TE
    Nat Commun 2016 Aug 22;7:12484
  • DNMT3A Loss Drives Enhancer Hypomethylation in FLT3-ITD-Associated Leukemias
    Yang L, Rodriguez B, Mayle A, Park HJ, Lin X, Luo M, Jeong M, Curry CV, Kim SB, Ruau D, Zhang X, Zhou T, Zhou M, Rebel VI, Challen GA, Gottgens B, Lee JS, Rau R, Li W, Goodell MA
    Cancer Cell 2016 Jun 13;29(6):922-934
  • Reprogrammable CRISPR/Cas9-Based System for Inducing Site-Specific DNA Methylation
    McDonald JI, Celik H, Rois LE, Fishberger G, Fowler T, Rees R, Kramer A, Martens A, Edwards JR, Challen GA
    Biol Open 2016 Jun 15;5(6):866-74
  • Enforced Differentiation of Dnmt3a-Null Bone Marrow Leads to Failure With c-Kit Mutations Driving Leukemic Transformation
    Celik H, Mallaney C, Kothari A, Ostrander EL, Eultgen E, Martens A, Miller CA, Hundal J, Klco JM, Challen GA
    Blood 2015 Jan 22;125(4):619-28
  • Dnmt3a Loss Predisposes Murine Hematopoietic Stem Cells to Malignant Transformation
    Mayle A, Yang L, Rodriguez B, Zhou T, Chang E, Curry CV, Challen GA, Li W, Wheeler D, Rebel VI, Goodell MA
    Blood 2015 Jan 22;125(4):629-38
  • Type II Interferon Promotes Differentiation of Myeloid-Biased Hematopoietic Stem Cells
    Matatall KA, Shen CC, Challen GA, King KY
    Stem Cells 2014 Nov;32(11):3023-30
  • Dnmt3a and Dnmt3b Have Overlapping and Distinct Functions in Hematopoietic Stem Cells
    Challen GA, Sun D, Mayle A, Jeong M, Luo M, Rodriguez B, Mallaney C, Celik H, Yang L, Xia Z, Cullen S, Berg J, Zheng Y, Darlington GJ, Li W, Goodell MA
    Cell Stem Cell 2014 Sep 4;15(3):350-64
  • Clonal-Level Responses of Functionally Distinct Hematopoietic Stem Cells to Trophic Factors
    Mallaney C, Kothari A, Martens A, Challen GA
    Exp Hematol 2014 Apr;42(4):317-327e2
  • Large Conserved Domains of Low DNA Methylation Maintained by Dnmt3a
    Jeong M, Sun D, Luo M, Huang Y, Challen GA, Rodriguez B, Zhang X, Chavez L, Wang H, Hannah R, Kim SB, Yang L, Ko M, Chen R, Gottgens B, Lee JS, Gunaratne P, Godley LA, Darlington GJ, Rao A, Li W, Goodell MA
    Nat Genet 2014 Jan;46(1):17-23
  • Dnmt3a Is Essential for Hematopoietic Stem Cell Differentiation
    Challen GA, Sun D, Jeong M, Luo M, Jelinek J, Berg JS, Bock C, Vasanthakumar A, Gu H, Xi Y, Liang S, Lu Y, Darlington GJ, Meissner A, Issa JP, Godley LA, Li W, Goodell MA
    Nat Genet 2011 Dec 4;44(1):23-31
  • Investigating the Role of Hematopoietic Stem and Progenitor Cells in Regulating the Osteogenic Differentiation of Mesenchymal Stem Cells in Vitro
    Liao J, Hammerick KE, Challen GA, Goodell MA, Kasper FK, Mikos AG
    J Orthop Res 2011 Oct;29(10):1544-53
  • Distinct Hematopoietic Stem Cell Subtypes Are Differentially Regulated by TGF-Beta1
    Challen GA, Boles NC, Chambers SM, Goodell MA
    Cell Stem Cell 2010 Mar 5;6(3):265-78
  • Runx1 Isoforms Show Differential Expression Patterns During Hematopoietic Development but Have Similar Functional Effects in Adult Hematopoietic Stem Cells
    Challen GA, Goodell MA
    Exp Hematol 2010 May;38(5):403-16
  • Promiscuous Expression of H2B-GFP Transgene in Hematopoietic Stem Cells
    Challen GA, Goodell MA
    PLoS One 2008 Jun 4;3(6):e2357
  • Kidney Side Population Reveals Multilineage Potential and Renal Functional Capacity but Also Cellular Heterogeneity
    Challen GA, Bertoncello I, Deane JA, Ricardo SD, Little MH
    J Am Soc Nephrol 2006 Jul;17(7):1896-912
  • Definition and Spatial Annotation of the Dynamic Secretome During Early Kidney Development
    Martinez G, Georgas K, Challen GA, Rumballe B, Davis MJ, Taylor D, Teasdale RD, Grimmond SM, Little MH
    Dev Dyn 2006 Jun;235(6):1709-19
  • Temporal and Spatial Transcriptional Programs in Murine Kidney Development
    Challen G, Gardiner B, Caruana G, Kostoulias X, Martinez G, Crowe M, Taylor DF, Bertram J, Little M, Grimmond SM
    Physiol Genomics 2005 Oct 17;23(2):159-71
  • Identifying the Molecular Phenotype of Renal Progenitor Cells
    Challen GA, Martinez G, Davis MJ, Taylor DF, Crowe M, Teasdale RD, Grimmond SM, Little MH
    J Am Soc Nephrol 2004 Sep;15(9):2344-57

Invited Publications

  • Clonal Hematopoiesis: Mechanisms Driving Dominance of Stem Cell Clones
    Challen GA, Goodell MA
    Blood 2020 Oct 1;136(14):1590-1598
  • Dominating the Negative: How DNMT3A Mutations Contribute to AML Pathogenesis
    Challen GA
    Cell Stem Cell 2017 Jan 5;20(1):7-8
  • The Epigenetic Basis of Hematopoietic Stem Cell Aging
    Kramer A, Challen GA
    Semin Hematol 2017 Jan;54(1):19-24
  • Inflammatory Signals in HSPC Development and Homeostasis: Too Much of a Good Thing?
    Luis TC, Tremblay CS, Manz MG, North TE, King KY, Challen GA
    Exp Hematol 2016 Oct;44(10):908-12
  • DNA Methylation in Normal and Malignant Hematopoiesis
    Celik H, Kramer A, Challen GA
    Int J Hematol 2016 Jun;103(6):617-626
  • Two New Routes to Make Blood: Hematopoietic Specification From Pluripotent Cell Lines Versus Reprogramming of Somatic Cells
    Singbrant S, van Galen P, Lucas D, Challen G, Rossi DJ, Daley GQ
    Exp Hematol 2015 Sep;43(9):756-759
  • Role of DNA Methyltransferases and DNA Methylation in Cell Fate Decisions During Blood Cell Development and Leukemia
    Challen GA, Trowbridge JJ
    In: Transcriptional and Epigenetic Mechanisms Regulating Normal and Aberrant Blood Cell Development (Bonifer C, Cockerill P, Eds), Springer Publishing 2014
  • Isolation and Characterization of Mouse Side Population Cells
    Ergen AV, Jeong M, Lin KK, Challen GA, Goodell MA
    Methods Mol Biol 2013;946:151-62
  • Hematopoietic Stem Cell Properties, Markers, and Therapeutics
    Lin KK, Challen GA, Goodell MA
    In: Principles of Regenerative Medicine. Elsevier/Academic Press 2011, pp 273-284
  • Bridge Over Troubled Stem Cells
    Challen GA, Goodell MA
    Mol Ther 2011 Oct;19(10):1756-8
  • The Potential of the Side Population in Regenerative Nephrology
    Little MH, Challen GA
    In: Regenerative Nephrology (Goligorsky, ed), Academic Press 2011
  • Hematopoietic Stem Cell Characterization and Isolation
    Rossi L, Challen GA, Sirin O, Lin KK, Goodell MA
    Methods Mol Biol 2011;750:47-59
  • Where New Approaches Can Stem From: Focus on Stem Cell Identification
    Adams V, Challen GA, Zuba-Surma E, Ulrich H, Vereb G, Tarnok A
    Cytometry A 2009 Jan;75(1):1-3
  • Mouse Hematopoietic Stem Cell Identification and Analysis
    Challen GA, Boles N, Lin KK, Goodell MA
    Cytometry A 2009 Jan;75(1):14-24
  • A Side Order of Stem Cells: The SP Phenotype
    Challen GA, Little MH
    Stem Cells 2006 Jan;24(1):3-12
  • Post-Transcription Regulation of mRNA and Hormone Synthesis and Release at the Anterior Pituitary Gland: Information Derived From the Recovery of Pituitary Gonadotrope Cell Function After Therapy With a GnRH Agonist
    D’Occhio MJ, Challen GA, Braga DPAF, Aspden WJ, Trigg TE
    Ann Rev Bio Sci 2000;2:91-112

Movies