• Researcher Profile

    Kimberly Stegmaier, MD

     
    Kimberly Stegmaier, MD
     
    Co-Director of the Pediatric Hematologic Malignancy Program
    Physician


    Associate Professor of Pediatrics, Harvard Medical School

    Center/Program

    Pediatric Hematologic Malignancies

    Office phone: 617-632-4985
    Fax: 617-632-4850
    Email: kimberly_stegmaier@dfci.harvard.edu

    Preferred contact method: email

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    Research Department

    Pediatric Oncology

    Interests

    Chemical screening, Neuroblastoma, Ewing Sarcoma, Hematologic malignancies, Cancer genomics

    Area of Research

    Principal Investigator


    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana 630D
    Boston, MA 02215

    Biography

    Kimberly Stegmaier, M.D., is an Associate Professor of Pediatrics at Harvard Medical School, a Principal Investigator in Pediatric Oncology at the Dana-Farber Cancer Institute (DFCI), and anAttending Physician at the Boston Children’s Hospital Boston (BCH) and DFCI. She is the Co-director of the Pediatric Hematologic Malignancies Program at DFCI and BCH and is also an Associate Member of the Broad Institute of Harvard and MIT. She received her B.S. from Duke University and her M.D. from Harvard Medical School. She completed her residency at BCH and a post-doctoral pediatric hematology-oncology fellowship at DFCI/BCH. In 2006, she launched her own laboratory effort at DFCI.

    Dr. Stegmaier’s laboratory integrates chemical biology, genomic, and proteomic approaches to discover new lead compounds and protein targets for cancer therapy. She has focused her efforts on the acute leukemias and two pediatric solid tumors of childhood: Ewing sarcoma and neuroblastoma.

    Recent Awards

    • Clifford Barger Excellence in Mentoring Award, Harvard Medical School, 2014
    • Osler Young Investigator Award, Interurban Clinical Club, 2013
    • Society for Pediatric Research (SPR) Young Investigator Award, 2012
    • Stephen E. Sallan Leadership Award, 2012
    • American Society for Clinical Investigation, Elected Member, 2009
    • SU2C Innovative Research Grant Recipient, 2009
    • Genome Technology “Tomorrow’s Principal Investigator” Award, 2007
    • Joanne Levy, MD, Memorial Award for Outstanding Achievement, American Society of  Hematology, 2006

    Research

    Principal Investigator


    My research program focuses on the integration of “omic” approaches for the identification of new protein targets and small-molecule modulators of malignancy with an eye toward clinical translation. Cancer discovery efforts in my laboratory have focused on the alteration of the malignant state (e.g., AML and neuroblastoma differentiation) and the modulation of pharmacologically challenging oncoproteins (e.g., EWS/FLI in Ewing sarcoma, MYCN in neuroblastoma, and NOTCH1 in T-ALL.) Most recently, we are applying an integrated approach to discover new therapeutic opportunities in these malignancies with deep genomic characterization of primary tumors, kinase activity profiling for immediately druggable targets, functional genomic screening for new tumor dependencies and chemical screening for modulators of relevant oncogenic drivers. Clinical trials for patients with AML and Ewing sarcoma have resulted from our research and a trial testing BET bromodomain inhibitors in patients with MYCN amplified neuroblastoma is in development.


     

    Select Publications

    • Stegmaier K, Ross KN, Colavito SA, OMalley S, Stockwell BR, Golub TR. Gene expression-based high- throughput screening (GE-HTS) and application to leukemia differentiation. Nature Genetics 2004;36:257-263.
    • Stegmaier K, Corsello SM, Ross KN, Wong JS, DeAngelo DJ, Golub TR. Gefitinib induces myeloid differentiation of acute myeloid leukemia, Blood 2005;106:2841-2848.  
    • Peck D, Crawford ED, Ross KN, Stegmaier K, Golub TR, and Lamb J. A method for high-throughput gene expression signature analysis. Genome Biol 2006;7:R61.1-R61.6.  
    • Hieronymus H, Lamb J, Ross KN, Peng XP, Clement C, Rodina A, Nieto M, Du J, Stegmaier K, Raj SM, Maloney KN, Clardy J, Hahn WC, Chiosis G, Golub TR. Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell 2006; 10:321-330.
    • Stegmaier K, Wong JS, Ross KN, Chow KT, Peck D, Wright WD, Lessnick SL, Kung AL, Golub TR. Signature-based small molecule screening identifies cytosine arabinoside as an EWS/FLI modulator in ewing sarcoma. PLoS Medicine 2007; 4(4):e122: 0702-0714 
    • Febbo PG, Mulligan MG, Slonina DA, Stegmaier K, Di Vizio D, Martinez P, Loda M, Taylor SC.Literature lab: a method of automated literature interrogation to infer biology from microarray analysis. BMC Genomics 2007; 8:461.
    • Hahn CK, Ross KN, Warrington IM, Mazitschek R, Kanegai CM, Wright RD, Kung AL, Golub TR, Stegmaier K. Expression-based screening identifies the combination of histone deacetylase inhibitors and retinoids for neuroblastoma differentiation. Proc Natl Acad Sci U S A 2008; 105:9751-9756. PMID: 18607002. 
    • Haining WN, Angelosanto J, Brosnahan K, Ross, K. Hahn C, Russell K, Drury L, Norton S, Nadler L, Stegmaier K. High-throughput gene expression profiling of memory differentiation in primary human T cells. BMC immunology 2008;9:44. PMID: 18673556.  
    • DuBois SG, Krailo MD, Lessnick SL, Smith R, Chen Z, Marina N, Grier HE. Stegmaier K. Phase II study of intermediate-dose cytarabine in patients with relapsed or refractory Ewing sarcoma: a report from the Children's Oncology Group. Pediatr Blood Cancer 2009;52:324-327.
    • Corsello SM, Roti G, Ross KN, Chow KT, Galinsky I, DeAngelo DJ, Stone RM, Kung AL, Golub TR, and Stegmaier K. Identification of AML1-ETO Modulators by Chemical Genomics. Blood 2009;113:6193-6205. PMID: 19377049  
    • Hahn CK, Berchuck JE, Ross KN, Kakoza RM, Clauser K, Schinzel AC , Ross L, Galinsky I, Davis TN, Silver SJ , Root DE, Stone RM, DeAngelo DJ, Carroll M, Hahn WC, Carr SA, Golub TR, Kung AL, and Stegmaier K. Proteomic and Genetic Approaches Identify Syk as an AML Target. Cancer Cell 2009; 16:281-294.
    • Banerji V, Frumm SM, Ross KN, Li LS, Schinzel AC, Hahn CK, Kakoza RM, Chow KT, Ross L, Alexe G, Tolliday N, Inguilizian H, Galinsky I, Stone RM, DeAngelo DJ, Roti G, Aster JC, Hahn WC, Kung AL, and Stegmaier K. Intersecting Chemical Genomic and Genetic Screens Identifies GSK-3α as a Target in Human AML. J Clin Invest 2012;122:935-947.
    • Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, Nekritz EA, Zeid R,Gustafson WC, Greninger P,Garnett MJ,McDermott U, Benes CH, Kung AL, Weiss WA, Bradner JE, Stegmaier K. Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition. Cancer Discovery 2013; 3:308-23. doi: 10.1158/2159-8290.CD-12-0418. Epub 2013.  
    • Roti G, Carlton A, Ross KN, Markstein M, Pajcini K, Su AH, Perrimon N, Pear WS, Kung AL, Blacklow SG, Aster JC, Stegmaier K. Complementary Genomic Screens Identify SERCA as a Therapeutic Target in NOTCH1 Mutated Cancer. Cancer Cell Mar 18;23(3):390-405. doi: 10.1016/j.ccr.2013.01.015. Epub 2013.
    • Crompton B, Carlton A, Thorner A, Christie A, Du J, Calicchio M, N Rivera M, Fleming M, Kohl N, Kung A, Stegmaier K. High-throughput tyrosine kinase activity profiling identifies FAK as a candidate therapeutic target in Ewing sarcoma. Cancer Res. 2013 May 1;73:2873-83. doi: 10.1158/0008-5472.CAN-12-1944. Epub 2013. 
    • Carnevale J, Ross L, Puissant A, Banerji V, Ross KN, Stegmaier K. SYK Regulates mTOR Signaling in AML.  Leukemia 2013; doi: 10.1038/leu.201389. [Epub ahead of print].    
    • Frumm SM, Fan ZP, Ross KN, Duvall JR, Gupta S, VerPlank L, Suh B-C, Holson E, Florence F. Wagner FF, Smith WB, Paranal RM, Bassil CF, Qi J, Roti G, Kung AL, Bradner JE, Tolliday N, Stegmaier K.  Selective HDAC/HDAC2 Inhibitors Induce Neuroblastoma Differentiation.  Chemistry & Biology 2013;20:713-725.
    • DeAngelo DJ, Neuberg D, Amrein PC, Berchuck J, Wadleigh M, Sirulnik LA, Galinsky I, Golub T, Stegmaier K, Stone RM.  A Phase II Study of the EGFR inhibitor gefitnib in patients with acute myeloid leukemia.  Leukemia Research 2013;pii: S0145-2126(13)00384-6. doi: 10.1016/j.leukres.2013.10.026. [Epub ahead of print].
    • Liu, S, Yin, L, Stroopinsky, D, Puissant, A, Stegmaier, K, Avigan, D, Kharbanda, S, Kufe, D, and Stone, R. MUC1-C Oncoprotein Promotes Mutant FLT3 Receptor Activation in Acute Myeloid Leukemia Cells. Blood 2014;123:734-42. doi: 10.1182/blood-2013-04-493858. Epub 2013 Nov 26.
    • Puissant A, Fenouille N, Alexe G, Pikman Y, Bassil CB, Mehta S, Du J, Kazi J, Luciano F, Ronnstrand L, Kung AL, Aster JC, Galinsky I, Stone RM, DeAngelo DJ, Hemman MT, Stegmaier K. SYK Is a Critical Regulator of FLT3 in Acute Myeloid Leukemia.  Cancer Cell;2014: 25:226-242. doi: 10.1016/j.ccr.2014.01.022.
    • Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ,  Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL,Root DE, Bradner JE, Aster JC, Kelliher  MA Bernstein BE.  An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nature Genetics 2014: doi:10.1038/ng.2913. [Epub ahead of print]. 
    • Lane AA, Chapuy B, Lin CY, Tivey T, Li H, Townsend EC, van Bodegom D, Day TA, Wu SC, Liu H, Yoda A. Alexe G, Schinzel AC, Sullivan TJ, Malinge S, Taylor JE, Stegmaier K, Jaffe JD, Bustin M, Te Kronnie G, Izraeli S, Harris MH, Stevenson KE, Neuberg D, Silverman LB, Sallan SE, Bradner JE, Hahn WC, Crispino JD, Pellman D, Weinstock DM.  Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation. Nat Genet; 2014. doi: 10.1038/ng.2949. [Epub ahead of print]. 

    Trainees

    • Crompton, Brian, MD
    • Roti, Giovanni, MD, Ph.D.
    • Banerji, Versha, MD, FRCP(c)
    • Pikman, Yana, M.D.
    • Puissant, Alexandre, Ph.D.
    • Chen, Liying, Ph.D.
    • Thorner, Aaron, Ph.D.
    • Carnevale, Julia, HHMI Fellow, HMS Medical Student
    • Li, Puyao C., HST/MIT-Harvard Student
    • Vallurupalli, Mounica, HHMI Fellow, HMS Medical Student
    • Patel, Sarvagna, HST Harvard/MIT Student
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