Photo of Kimberly Stegmaier,  MD

Kimberly Stegmaier, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4438
Fax: (617) 632-4850


kimberly_stegmaier@dfci.harvard.edu

Kimberly Stegmaier, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Pediatrics, Harvard Medical School
  • Attending Physician, Pediatric Oncology, Boston Children's Hospital
  • Principal Investigator, Pediatric Oncology, Dana-Farber Cancer Institute
  • Co-Director, Pediatric Hematologic Malignancy Program, Boston Children's Hospital and Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Member, Center Scientific Council

Research Abstract

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.

Publications

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  • Pikman Y, Puissant A, Alexe G, Furman A, Chen LM, Frumm SM, Ross L, Fenouille N, Bassil CF, Lewis CA, Ramos A, Gould J, Stone RM, DeAngelo DJ, Galinsky I, Clish CB, Kung AL, Hemann MT, Vander Heiden MG, Banerji V, Stegmaier K. Targeting MTHFD2 in acute myeloid leukemia. J Exp Med 2016; 213:1285-306. PubMed
  • Aguirre AJ, Meyers RM, Weir BA, Vazquez F, Zhang CZ, Ben-David U, Cook A, Ha G, Harrington WF, Doshi MB, Kost-Alimova M, Gill S, Xu H, Ali LD, Jiang G, Pantel S, Lee Y, Goodale A, Cherniack AD, Oh C, Kryukov G, Cowley GS, Garraway LA, Stegmaier K, Roberts CW, Golub TR, Meyerson M, Root DE, Tsherniak A, Hahn WC. Genomic copy number dictates a gene-independent cell response to CRISPR-Cas9 targeting. 2016. PubMed
  • Wagner FF, Bishop JA, Gale JP, Shi X, Walk M, Ketterman J, Patnaik D, Barker D, Walpita D, Campbell AJ, Nguyen S, Lewis M, Ross L, Weïwer M, An WF, Germain AR, Nag PP, Metkar S, Kaya T, Dandapani S, Olson DE, Barbe AL, Lazzaro F, Sacher JR, Cheah JH, Fei D, Perez J, Munoz B, Palmer M, Stegmaier K, Schreiber SL, Scolnick E, Zhang YL, Haggarty SJ, Holson EB, Pan JQ. Inhibitors of Glycogen Synthase Kinase 3 with Exquisite Kinome-Wide Selectivity and Their Functional Effects. ACS Chem Biol 2016. PubMed
  • Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekoffer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LaBoeuf N, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell 2016; 29:574-86. PubMed
  • Harris MH, DuBois SG, Glade Bender JL, Kim A, Crompton BD, Parker E, Dumont IP, Hong AL, Guo D, Church A, Stegmaier K, Roberts CW, Shusterman S, London WB, MacConaill LE, Lindeman NI, Diller L, Rodriguez-Galindo C, Janeway KA. Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors: The Individualized Cancer Therapy (iCat) Study. JAMA Oncol 2016. PubMed
  • Hong AL, Tseng YY, Cowley GS, Jonas O, Cheah JH, Kynnap BD, Doshi MB, Oh C, Meyer SC, Church AJ, Gill S, Bielski CM, Keskula P, Imamovic A, Howell S, Kryukov GV, Clemons PA, Tsherniak A, Vazquez F, Crompton BD, Shamji AF, Rodriguez-Galindo C, Janeway KA, Roberts CW, Stegmaier K, van Hummelen P, Cima MJ, Langer RS, Garraway LA, Schreiber SL, Root DE, Hahn WC, Boehm JS. Integrated genetic and pharmacologic interrogation of rare cancers. Nat Commun 2016; 7:11987. PubMed
  • Neumann T, Benajiba L, Göring S, Stegmaier K, Schmidt B. Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia. J Med Chem 2015; 58:8907-19. PubMed
  • Stieglitz E, Taylor-Weiner AN, Chang TY, Gelston LC, Wang YD, Mazor T, Esquivel E, Yu A, Seepo S, Olsen SR, Rosenberg M, Archambeault SL, Abusin G, Beckman K, Brown PA, Briones M, Carcamo B, Cooper T, Dahl GV, Emanuel PD, Fluchel MN, Goyal RK, Hayashi RJ, Hitzler J, Hugge C, Liu YL, Messinger YH, Mahoney DH, Monteleone P, Nemecek ER, Roehrs PA, Schore RJ, Stine KC, Takemoto CM, Toretsky JA, Costello JF, Olshen AB, Stewart C, Li Y, Ma J, Gerbing RB, Alonzo TA, Getz G, Gruber TA, Golub TR, Stegmaier K, Loh ML. The genomic landscape of juvenile myelomonocytic leukemia. Nat Genet 2015; 47:1326-33. PubMed
  • Kennedy AL, Vallurupalli M, Chen L, Crompton B, Cowley G, Vazquez F, Weir BA, Tsherniak A, Parasuraman S, Kim S, Alexe G, Stegmaier K. Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma. 2015. PubMed
  • Deveau AP, Forrester AM, Coombs AJ, Wagner GS, Grabher C, Chute IC, Léger D, Mingay M, Alexe G, Rajan V, Liwski R, Hirst M, Steigmaier K, Lewis SM, Look AT, Berman JN. Epigenetic therapy restores normal hematopoiesis in a zebrafish model of NUP98-HOXA9-induced myeloid disease. Leukemia 2015. PubMed
  • Boros K, Puissant A, Back M, Alexe G, Bassil CF, Sinha P, Tholouli E, Stegmaier K, Byers RJ, Rodig SJ. Increased SYK activity is associated with unfavorable outcome among patients with acute myeloid leukemia. 2015; 6:25575-87. PubMed
  • Marques Howarth M, Simpson D, Ngok SP, Nieves B, Chen R, Siprashvili Z, Vaka D, Breese MR, Crompton BD, Alexe G, Hawkins DS, Jacobson D, Brunner AL, West R, Mora J, Stegmaier K, Khavari P, Sweet-Cordero EA. Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis. J Clin Invest 2014; 124:5275-90. PubMed
  • Crompton BD, Stewart C, Taylor-Weiner A, Alexe G, Kurek KC, Calicchio ML, Kiezun A, Carter SL, Shukla SA, Mehta SS, Thorner AR, de Torres C, Lavarino C, Suñol M, McKenna A, Sivachenko A, Cibulskis K, Lawrence MS, Stojanov P, Rosenberg M, Ambrogio L, Auclair D, Seepo S, Blumenstiel B, DeFelice M, Imaz-Rosshandler I, Schwarz-Cruz Y Celis A, Rivera MN, Rodriguez-Galindo C, Fleming MD, Golub TR, Getz G, Mora J, Stegmaier K. The genomic landscape of pediatric Ewing sarcoma. 2014. PubMed
  • Moore NF, Azarova AM, Bhatnagar N, Ross KN, Drake LE, Frumm S, Liu QS, Christie AL, Sanda T, Chesler L, Kung AL, Gray NS, Stegmaier K, George RE. Molecular rationale for the use of PI3K/AKT/mTOR pathway inhibitors in combination with crizotinib in ALK-mutated neuroblastoma. 2014; 5:8737-49. PubMed
  • 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. PubMed
  • Stegmaier K. Targeting Csnk1a1 in leukemia. J Exp Med 2014; 211:594. PubMed
  • 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 gefitinib in patients with acute myeloid leukemia. Leuk Res 2014; 38:430-4. PubMed
  • 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. Nat Genet 2014; 46:364-70. PubMed
  • Puissant A, Fenouille N, Alexe G, Pikman Y, Bassil CF, Mehta S, Du J, Kazi JU, Luciano F, Rönnstrand L, Kung AL, Aster JC, Galinsky I, Stone RM, DeAngelo DJ, Hemann MT, Stegmaier K. SYK is a critical regulator of FLT3 in acute myeloid leukemia. Cancer Cell 2014; 25:226-42. PubMed
  • Liu S, Yin L, Stroopinsky D, Rajabi H, Puissant A, Stegmaier K, Avigan D, Kharbanda S, Kufe D, Stone R. MUC1-C oncoprotein promotes FLT3 receptor activation in acute myeloid leukemia cells. Blood 2014; 123:734-42. PubMed
  • Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, McKenna A, Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N, Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortés ML, Auclair D, Saksena G, Voet D, Noble M, DiCara D, Lin P, Lichtenstein L, Heiman DI, Fennell T, Imielinski M, Hernandez B, Hodis E, Baca S, Dulak AM, Lohr J, Landau DA, Wu CJ, Melendez-Zajgla J, Hidalgo-Miranda A, Koren A, McCarroll SA, Mora J, Lee RS, Crompton B, Onofrio R, Parkin M, Winckler W, Ardlie K, Gabriel SB, Roberts CW, Biegel JA, Stegmaier K, Bass AJ, Garraway LA, Meyerson M, Golub TR, Gordenin DA, Sunyaev S, Lander ES, Getz G. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013; 499:214-8. PubMed
  • Miller PG, Al-Shahrour F, Hartwell KA, Chu LP, Järås M, Puram RV, Puissant A, Callahan KP, Ashton J, McConkey ME, Poveromo LP, Cowley GS, Kharas MG, Labelle M, Shterental S, Fujisaki J, Silberstein L, Alexe G, Al-Hajj MA, Shelton CA, Armstrong SA, Root DE, Scadden DT, Hynes RO, Mukherjee S, Stegmaier K, Jordan CT, Ebert BL. In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling. Cancer Cell 2013; 24:45-58. PubMed
  • Crompton BD, Carlton AL, Thorner AR, Christie AL, Du J, Calicchio ML, Rivera MN, Fleming MD, Kohl NE, Kung AL, Stegmaier K. High-throughput tyrosine kinase activity profiling identifies FAK as a candidate therapeutic target in Ewing sarcoma. Cancer Res 2013. PubMed
  • Roti G, Carlton A, Ross KN, Markstein M, Pajcini K, Su AH, Perrimon N, Pear WS, Kung AL, Blacklow SC, Aster JC, Stegmaier K. Complementary genomic screens identify SERCA as a therapeutic target in NOTCH1 mutated cancer. Cancer Cell 2013; 23:390-405. PubMed
  • 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. 2013; 3:308-23. PubMed
  • Stegmaier K. Chemical genomics and combo therapy. Blood 2010; 116:5786-8. PubMed
  • Aste-Amézaga M, Zhang N, Lineberger JE, Arnold BA, Toner TJ, Gu M, Huang L, Vitelli S, Vo KT, Haytko P, Zhao JZ, Baleydier F, L'Heureux S, Wang H, Gordon WR, Thoryk E, Andrawes MB, Tiyanont K, Stegmaier K, Roti G, Ross KN, Franlin LL, Wang H, Wang F, Chastain M, Bett AJ, Audoly LP, Aster JC, Blacklow SC, Huber HE. Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors. PLoS ONE 2010; 5:e9094. PubMed
  • 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, Stegmaier K. Proteomic and genetic approaches identify Syk as an AML target. Cancer Cell 2009; 16:281-94. PubMed
  • Corsello SM,Roti G,Ross KN,Chow KT,Galinsky I,Deangelo DJ,Stone RM,Kung AL,Golub TR,Stegmaier K. Identification of AML1-ETO modulators by chemical genomics. Blood 2009; 113:6193-205. PubMed
  • 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 2008; 52:324-7. PubMed
  • 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; 105:9751-6. PubMed
  • 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 Immunol 2008; 9:44. PubMed
  • 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; 10:321-30. PubMed
  • Peck D, Crawford ED, Ross KN, Stegmaier K, Golub TR, Lamb J. A Method for High-Throughput Gene Expression Signature Analysis. Genome Biol 2006; 7:R61. PubMed
  • Stegmaier K. Genomic approaches in acute leukemia. Best Pract Res Clin Haematol 2006; 19:263-8. PubMed
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