Scott Armstrong, MD, PhD

Department	Hematology/Oncology
Hospital Title	Associate in Medicine
Academic Title	Associate Professor of Pediatrics
Phone	617-919-2508
Fax	617-730-0934
Email	Scott Armstrong
Location	300 Longwood Avenue Karp-08211 Boston MA 02115

Research Overview

The goal of Dr. Scott Armstrong's research program is to define genetic and epigenetic programs that control the extensive self renewal properties associated with leukemia and other cancers. This knowledge is then used to develop rational approaches for new therapeutic development. Experiments incorporate the use of sophisticated mouse models of leukemia and characterization of human leukemia cells. Current active research areas include:

• Identification of developmental pathways that are responsible for cancer stem cell self-renewal and characterization of their specific roles in this process.
• Characterization of histone methylation in leukemias, and assessment of the role of specific histone methyltransferases as potential therapeutic targets in leukemia.
• Development of mouse models for testing novel therapeutic approaches
• Detailed genomic characterization of human and mouse leukemias through the use of next generation sequencing approaches.

Dr. Armstrong's lab recently identified leukemia stem cells in a model of human leukemia and demonstrated that acute myelogenous leukemia stem cells express a stem cell program in the context of a more differentiated cell type. This finding has important implications for therapeutic approaches that will target cancer stem cells. His lab also defined changes in chromosome structure as a critical initial step in leukemia development. These findings have prompted a search for therapies that can reverse this process and eradicate leukemia stem cells. Dr Armstrong's work is driven by questions that are of immediate clinical relevance and a number of clinical trials have been developed as a direct result of this work.

About Scott Armstrong

Scott Armstrong received an MD and PhD from the University of Texas Southwestern Medical School. He completed an internship and residency at Children's Hospital Boston and a fellowship at Children's Hospital Boston/Dana-Farber Cancer Institute. He is currently Co-director of the Harvard Stem Cell Institute Cancer Program and Co-director of the Leukemia program in the Dana-Farber Harvard Cancer Center. He received the Wilson S. Stone Memorial Award from the M.D. Anderson Cancer Center in 2006, which recognizes a young researcher who has made outstanding contributions to biomedical sciences in the United States, and received the McCulloch and Till Award from the International Society of Experimental Hematology in 2009, which recognizes emerging international leaders in stem cell biology.

Key Publications

• Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV, Feng Z, Punt N, Daigle A, Bullinger L, Pollock RM, Richon VM, Kung AL, Armstrong SA. MLL-rearranged Leukemia is Dependent on Aberrant H3K79 Methylation by DOT1L. Cancer Cell 2011, Jul 12;20(1)66-78.
• Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnson LD, Scott MP, Smith JJ, Xiao Y, Jin L, Kuntz KW, Chesworth R, Moyer MP, Bernt KM, Tsend JC, Kung AL, Armstrong SA, Copeland RA, Richon VM, Pollock RM. Selective Killing of Mixed Lineage Leukemia Cells by a Potent Small-Molecule DOT1L Inhibitor. Cancer Cell 2011, Jul 12;20(1)53-65.
• Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science. 2010 Mar 26;327(5973):1650-3.
• Krivtsov AV, Feng Z, Lemieux ME, Faber J, Vempati S, Sinha AU, Xia X, Jesneck J, Bracken AP, Silverman LB, Kutok JL, Kung AL, Armstrong SA. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell. 2008 Nov 4; 15(5):355-68.
• Krivtsov, A.V., Armstrong S.A.: MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer. 2007 Nov;7(11):823-33.
• Wei, G., Twomey, D., Lamb, J., Agarwal, J., Stam, R., Opferman, J. T., Sallan, S.E., den Boer, M.L., Pieters, R., Golub, T.R., Armstrong, S.A.: Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance. Cancer Cell. 2006: 10, 331-42.
• Krivtsov, A.V., Twomey, D., Feng, Z., Stubbs, M.C., Wang, Y., Faber, J., Levine, J.E., Wang, J., Hahn, W.C., Gilliland, D.G., Golub, T.R., Armstrong, S.A.: Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006: 442, 818-22. (DOI: 10.1038/nature04980).
• Armstrong, S.A., Kung, A.L., Mabon, M.E., Silverman, L.B., Stam, R.W., den Boer, M.L., Pieters, R., Sallan, S.E., Kersey, J.H., Fletcher, J.A., Golub, T.R., Griffin, J.D., Korsmeyer, S.J.: Inhibition of FLT3 in MLL: Validation of a therapeutic target identified by gene expression based classification. Cancer Cell 2003; 3: 173-183.