Kimberly Stegmaier, MD
|Hospital Title||Assistant in Medicine|
|Academic Title||Assistant Professor of Pediatrics|
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Kimberly Stegmaier’s laboratory champions the importance of cancer target and therapy discovery in academic centers for malignancies affecting children not likely to be pursued by the pharmaceutical industry. Her research program focuses on the integration of genomic, genetic, and proteomic approaches to identify new protein targets and small-molecule modulators of malignancy with an eye toward clinical translation. In particular, she developed a chemical genomic approach to drug screening, Gene Expression-based High-throughput Screening (GE-HTS), in which gene expression signatures serve as surrogates for different biological states. This is a generic method and a departure from traditional target-based or phenotype-based screening. Her laboratory has applied the GE-HTS approach to the alteration of the malignant state (i.e., induction of acute myeloid leukemia (AML) and neuroblastoma differentiation) and to the modulation of intractable protein targets such as transcription factor abnormalities in Ewing sarcoma and T-cell acute lymphoblastic leukemia. Compounds emerging from screening efforts have served as clinical leads for trial development as well as tool compounds for probing mechanism of oncogenesis and for the identification of new cancer targets. Ongoing work in the laboratory focuses on applying these approaches to:
- Identification of new cancer-promoting protein targets
- Modulation of pharmacologicaly challenging oncoproteins (e.g., transcription factors)
- Identification of new small-molecule inducers of cancer cell differentiation
The laboratory’s ultimate goal is the translation of compelling findings to clinical trial. Clinical trials for AML and Ewing sarcoma have resulted from this research.
About Kimberly Stegmaier
Kimberly Stegmaier is a physician-scientist who received an MD from Harvard Medical School. She completed her Pediatrics internship/residency at Children's Hospital Boston and a Pediatric Hematology/Oncology fellowship at the Children's Hospital Boston/Dana-Farber Cancer Institute where she also served as the Chief Fellow. Dr. Stegmaier is an Assistant Professor in the Department of Pediatrics at Harvard Medical School, an independent investigator in Pediatric Oncology at the Dana-Farber Cancer Institute (DFCI), and an attending physician at the Children’s Hospital Boston (CHB) and DFCI. She is also an Associate Member of the Broad Institute of Harvard and MIT.
Dr. Stegmaier has been the recipient of an American Society of Hematology Fellow Scholar Award, Hood Foundation Child Health Research Grant, Sidney Kimmel Cancer Foundation Scholar Award, Smith Family New Investigator Award and HHMI Physician-Scientist Early Career Award. She was recently named a Stand-Up-to-Cancer Innovative Research Grant Recipient and received a number of other awards, including, the ASH Joanne Levy, MD, Memorial Award for Outstanding Achievement (2006), the 2007 Genome Technology “Tomorrow’s Principal Investigator” Award and the Society for Pediatric Research Young Investigator Award (2012). Outside of her scientific and clinical endeavors, Dr. Stegmaier has a passion for ballet and has performed professionally with Ballet Theater of Boston and the Cambridge Chamber Ballet.
- Stegmaier K, Pendse S, Barker G, Bray-Ward P, Ward DC, Montgomery KT, Krauter K, Reynolds C, Sklar J, Donnelly M, Bohlander SK, Rowley JD, Sallan SE, Gilliland DG, Golub TR. Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood. Blood 1995;86:38-44.
- Stegmaier K, Takeuchi S, Golub TR, Bohlander S, Bartram CR, Koeffler HP, Gilliland DG. Mutational analysis of the candidate tumor suppressor genes TEL and KIP1 in childhood acute lymphoblastic leukemia. Cancer Research 1996;56:1413-1417.
- McLean TW, Ringold S, Neuberg D, Stegmaier K, Tantravahi R, Ritz J, Koeffler HP, Takeuchi S, Janssen JWG, Seriu T, Bartram CR, Sallan SE, Gilliland DG, Golub TR. TEL/AML1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia. Blood 1996; 88:4252-4248.
- Stegmaier K, Ross KN, Colavito SA, O’Malley S, Stockwell BR, Golub TR. Gene expression-based high-throughput screening (GE-HTS) and application to leukemia differentiation. Nature Genetics 2004; 36:257-63.
- 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.
- Xu K, Guidez F, Glasow A, Chung D, Petrie K, Stegmaier K, Wang K, Zhang J, Jing Y, Zelent A, Waxman S. Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor a and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Research 2005;65: 7856-7865.
- Peck D, Crawford ED, Ross KN, Stegmaier K, Golub TR, and Lamb J. A method for high-throughput gene expression signature analysis. Genome Biology 2006; 19;7(7):R61.1-61.6.
- 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, and 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. PMID: 18989890.
- 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. PMID: 19800574.
- 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. PMID: 20161710.
- 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. PMID: 22326953.