Photo of Martin Sattler,  PhD

Martin Sattler, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4382
Fax: (617) 632-4388


martin_sattler@dfci.harvard.edu

Martin Sattler, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Instructor, Medical Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

My major interest is determining the role of the BCR/ABL oncogene in the pathogenesis of chronic myelogenous leukemia (CML). I have begun a systematic analysis of identifying the tyrosine phosphorylated targets of BCR/ABL. Through various methodologies, I have helped to identify several key targets of BCR/ABL, including c-CBL, SHP2, CRKL, the inostol 5-phosphatase SHIP, and their interaction with other signaling molecules. I have determined that SHIP is heavily tyrosine phosphorylated in CML cells and the level is reduced. Currently, I am determining the role of SHIP in CML cell signaling and its potential role in the myeloproliferative phenotype. Aside from dissecting the mechanism of SHIP activation in leukemic cells, I have begun to study this molecule's role in normal hematopoietic cells, especially B-cells. Through my interest in CML, I have also defined that ROS play an important role in hematopoiesis. My long term goal is to identify gene targets which can be up- or down-regulated in response to ROS.

Publications

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  • Nonami A, Sattler M, Weisberg E, Liu Q, Zhang J, Patricelli MP, Christie AL, Saur AM, Kohl NE, Kung AL, Yoon H, Sim T, Gray NS, Griffin JD. Identification of novel therapeutic targets in acute leukemias with NRAS mutations using a pharmacological approach. Blood 2015. PubMed
  • Weisberg E, Nonami A, Chen Z, Nelson E, Chen Y, Liu F, Cho H, Zhang J, Sattler M, Mitsiades C, Wong KK, Liu Q, Gray NS, Griffin JD. Upregulation of IGF1R by Mutant RAS in Leukemia and Potentiation of RAS Signaling Inhibitors by Small-Molecule Inhibition of IGF1R. Clin Cancer Res 2014. PubMed
  • Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, ten Hacken E, Bertilaccio MT, Antonini E, Neri A, Ponzoni M, Marcatti M, Richardson PG, Carrasco R, Kimmelman AC, Wong KK, Caligaris-Cappio F, Blandino G, Kuehl WM, Anderson KC, Tonon G. Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med 2014; 20:599-606. PubMed
  • Fan F, Tonon G, Bashari MH, Vallet S, Antonini E, Goldschmidt H, Schulze-Bergkamen H, Opferman JT, Sattler M, Anderson KC, Jäger D, Podar K. Targeting Mcl-1 for multiple myeloma (MM) therapy: drug-induced generation of Mcl-1 fragment Mcl-1(128-350) triggers MM cell death via c-Jun upregulation. Cancer Lett 2014; 343:286-94. PubMed
  • Salgia R, Sattler M. A new hope for precision medicine. Sci Transl Med 2013; 5:208fs38. PubMed
  • Toms AV, Deshpande A, McNally R, Jeong Y, Rogers JM, Kim CU, Gruner SM, Ficarro SB, Marto JA, Sattler M, Griffin JD, Eck MJ. Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases. Nat Struct Mol Biol 2013; 20:1221-3. PubMed
  • Weisberg E, Liu Q, Zhang X, Nelson E, Sattler M, Liu F, Nicolais M, Zhang J, Mitsiades C, Smith RW, Stone R, Galinsky I, Nonami A, Griffin JD, Gray N. Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cells. PLoS ONE 2013; 8:e56473. PubMed
  • Weisberg E, Sattler M. A novel combination therapy approach for the treatment of acute myeloid leukemia: the multi-kinase inhibitor sorafenib and the HDM2 inhibitor nutlin-3. Haematologica 2012; 97:1620-1. PubMed
  • Naramura M, Nadeau S, Mohapatra B, Ahmad G, Mukhopadhyay C, Sattler M, Raja SM, Natarajan A, Band V, Band H. Mutant Cbl proteins as oncogenic drivers in myeloproliferative disorders. 2011. PubMed
  • Fernandes MS, Reddy MM, Croteau NJ, Walz C, Weisbach H, Podar K, Band H, Carroll M, Reiter A, Larson RA, Salgia R, Griffin JD, Sattler M. Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism. J Biol Chem 2010; 285:32596-605. PubMed
  • Yoda A, Yoda Y, Chiaretti S, Bar-Natan M, Mani K, Rodig SJ, West N, Xiao Y, Brown JR, Mitsiades C, Sattler M, Kutok JL, DeAngelo DJ, Wadleigh M, Piciocchi A, Dal Cin P, Bradner JE, Griffin JD, Anderson KC, Stone RM, Ritz J, Foà R, Aster JC, Frank DA, Weinstock DM. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 2010; 107:252-7. PubMed
  • Tan YH, Krishnaswamy S, Nandi S, Kanteti R, Vora S, Onel K, Hasina R, Lo FY, El-Hashani E, Cervantes G, Robinson M, Kales SC, Lipkowitz S, Karrison T, Sattler M, Vokes EE, Wang YC, Salgia R. CBL is frequently altered in lung cancers: its relationship to mutations in MET and EGFR tyrosine kinases. PLoS ONE 2010; 5:e8972. PubMed
  • Sattler M, Griffin JD. JAK2 gets histone H3 rolling. Cancer Cell 2009; 16:365-6. PubMed
  • Krishnaswamy S, Kanteti R, Duke-Cohan JS, Loganathan S, Liu W, Ma PC, Sattler M, Singleton PA, Ramnath N, Innocenti F, Nicolae DL, Ouyang Z, Liang J, Minna J, Kozloff MF, Ferguson MK, Natarajan V, Wang YC, Garcia JG, Vokes EE, Salgia R. Ethnic differences and functional analysis of MET mutations in lung cancer. Clin Cancer Res 2009; 15:5714-23. PubMed
  • Fernandes MS, Reddy MM, Gonneville JR, DeRoo SC, Podar K, Griffin JD, Weinstock DM, Sattler M. BCR-ABL promotes the frequency of mutagenic single-strand annealing DNA repair. Blood 2009; 114:1813-9. PubMed
  • Zhang J, Sattler M, Tonon G, Grabher C, Lababidi S, Zimmerhackl A, Raab MS, Vallet S, Zhou Y, Cartron MA, Hideshima T, Tai YT, Chauhan D, Anderson KC, Podar K. Targeting angiogenesis via a c-Myc/hypoxia-inducible factor-1alpha-dependent pathway in multiple myeloma. Cancer Res 2009; 69:5082-90. PubMed
  • Rodrigues MS,Reddy MM,Sattler M. Cell cycle regulation by oncogenic tyrosine kinases in myeloid neoplasias: from molecular redox mechanisms to health implications. Antioxid Redox Signal 2008; 10:1813-48. PubMed
  • Wernig G, Gonneville JR, Crowley BJ, Rodrigues MS, Reddy MM, Hudon HE, Walz C, Reiter A, Podar K, Royer Y, Constantinescu SN, Tomasson MH, Griffin JD, Gilliland DG, Sattler M. The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes. Blood 2008; 111:3751-9. PubMed
  • Jagadeeswaran R, Surawska H, Krishnaswamy S, Janamanchi V, Mackinnon AC, Seiwert TY, Loganathan S, Kanteti R, Reichman T, Nallasura V, Schwartz S, Faoro L, Wang YC, Girard L, Tretiakova MS, Ahmed S, Zumba O, Soulii L, Bindokas VP, Szeto LL, Gordon GJ, Bueno R, Sugarbaker D, Lingen MW, Sattler M, Krausz T, Vigneswaran W, Natarajan V, Minna J, Vokes EE, Ferguson MK, Husain AN, Salgia R. Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion. Cancer Res 2008; 68:132-42. PubMed
  • Rodrigues MS, Sattler M. Chronic myelogenous leukemia progenitors display a genetically unstable personality. Journal of the National Cancer Institute 2007; 99:662-3. PubMed
  • Podar K, Raab MS, Tonon G, Sattler M, Baril. Up-Regulation of c-Jun Inhibits Proliferation and Induces Apoptosis via Caspase-Triggered c-Abl Cleavage in Human Multiple Myeloma. Cancer Res 2007; 67:1680-1688. PubMed
  • Podar K, Tonon G, Sattler M, Tai YT, Legouill S, Yasui H, Ishitsuka K, Kumar S, Kumar R, Pandite LN, Hideshima T, Chauhan D, Anderson KC. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proc Natl Acad Sci U S A 2006; 103:19478-83. PubMed
  • Walz C, Crowley BJ, Hudon HE, Gramlich JL, Neuberg DS, Podar K, Griffin JD, Sattler M. Activated Jak2 with the V617F point mutation promotes G1/S phase transition. J Biol Chem 2006; 281:18177-83. PubMed
  • Walz C, Sattler M. Novel targeted therapies to overcome imatinib mesylate resistance in chronic myeloid leukemia (CML). Crit Rev Oncol Hematol 2006; 57:145-64. PubMed
  • Sattler M, Walz C, Crowley BJ, Lengfelder E, J. A sensitive high-throughput method to detect activating mutations of Jak2 in peripheral-blood samples. Blood 2006; 107:1237-8. PubMed
  • Kim JH, Chu SC, Gramlich JL, Pride YB, Babendreier E, Chauhan D, Salgia R, Podar K, Griffin JD, Sattler M. Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species. Blood 2004; 105:1717-23. PubMed
  • Banerji L, Sattler M. Targeting mutated tyrosine kinases in the therapy of myeloid leukaemias. Expert Opin Ther Targets 2004; 8:221-39. PubMed
  • Sattler M, Salgia R. Targeting c-Kit mutations: basic science to novel therapies. Leuk Res 2004; 28 Suppl 1:S11-20. PubMed
  • Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, Johnson BE, Salgia R. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 2003; 63:6272-81. PubMed
  • Chauhan D, Li G, Sattler M, Podar K, Mitsiades C, Mitsiades N, Munshi N, Hideshima T, Anderson KC. Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells. Oncogene 2003; 22:6296-300. PubMed
  • Sattler M, Pride YB, Ma P, Gramlich JL, Chu SC, Quinnan LA, Shirazian S, Liang C, Podar K, Christensen JG, Salgia R. A novel small molecule met inhibitor induces apoptosis in cells transformed by the oncogenic TPR-MET tyrosine kinase. Cancer Res 2003; 63:5462-9. PubMed
  • Sattler M, Quinnan LR, Pride YB, Gramlich JL, Chu SC, Even GC, Kraeft SK, Chen LB, Salgia R. 2-methoxyestradiol alters cell motility, migration, and adhesion. Blood 2003; 102:289-96. PubMed
  • Sattler M, Griffin JD. Molecular mechanisms of transformation by the BCR-ABL oncogene. Semin Hematol 2003; 40:4-10. PubMed
  • Kijima T, Maulik G, Ma PC, Tibaldi EV, Turner RE, Rollins B, Sattler M, Johnson BE, Salgia R. Regulation of cellular proliferation, cytoskeletal function, and signal transduction through CXCR4 and c-Kit in small cell lung cancer cells. Cancer Res 2002; 62:6304-11. PubMed
  • Chauhan D, Catley L, Hideshima T, Li G, Leblanc R, Gupta D, Sattler M, Richardson P, Schlossman RL, Podar K, Weller E, Munshi N, Anderson KC. 2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells. Blood 2002; 100:2187-94. PubMed
  • Sattler M, Mohi MG, Pride YB, Quinnan LR, Malouf NA, Podar K, Gesbert F, Iwasaki H, Li S, Van Etten RA, Gu H, Griffin JD, Neel BG. Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell 2002; 1:479-92. PubMed
  • Podar K, Tai YT, Lin BK, Narsimhan RP, Sattler M, Kijima T, Salgia R, Gupta D, Chauhan D, Anderson KC. Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with beta 1 integrin- and phosphatidylinositol 3-kinase-dependent PKC alpha activation. J Biol Chem 2001; 277:7875-81. PubMed
  • Sattler M, Pride YB, Quinnan LR, Verma S, Malouf NA, Husson H, Salgia R, Lipkowitz S, Griffin JD. Differential expression and signaling of CBL and CBL-B in BCR/ABL transformed cells. Oncogene 2002; 21:1423-33. PubMed
  • Sattler M, Verma S, Pride YB, Salgia R, Rohrschneider LR, Griffin JD. SHIP1, an SH2 domain containing polyinositol-5-phosphatase, regulates migration through two critical tyrosine residues and forms a novel signaling complex with DOK1 and CRKL. J Biol Chem 2000; 276:2451-8. PubMed
  • Wang WL, Healy ME, Sattler M, Verma S, Lin J, Maulik G, Stiles CD, Griffin JD, Johnson BE, Salgia R. Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571. Oncogene 2000; 19:3521-8. PubMed
  • Sillaber C, Gesbert F, Frank DA, Sattler M, Griffin JD. STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells. Blood 2000; 95:2118-25. PubMed
  • Salgia R, Quackenbush E, Lin J, Souchkova N, Sattler M, Ewaniuk DS, Klucher KM, Daley GQ, Kraeft SK, Sackstein R, Alyea EP, von Andrian UH, Chen LB, Gutierrez-Ramos JC, Pendergast AM, Griffin JD. The BCR/ABL oncogene alters the chemotactic response to stromal-derived factor-1alpha. Blood 1999; 94:4233-46. PubMed
  • Sattler M, Verma S, Byrne CH, Shrikhande G, Winkler T, Algate PA, Rohrschneider LR, Griffin JD. BCR/ABL directly inhibits expression of SHIP, an SH2-containing polyinositol-5-phosphatase involved in the regulation of hematopoiesis. Mol Cell Biol 1999; 19:7473-80. PubMed
  • Sattler M, Winkler T, Verma S, Byrne CH, Shrikhande G, Salgia R, Griffin JD. Hematopoietic growth factors signal through the formation of reactive oxygen species. Blood 1999; 93:2928-35. PubMed
  • Salgia R, Li JL, Ewaniuk DS, Wang YB, Sattler M, Chen WC, Richards W, Pisick E, Shapiro GI, Rollins BJ, Chen LB, Griffin JD, Sugarbaker DJ. Expression of the focal adhesion protein paxillin in lung cancer and its relation to cell motility. Oncogene 1999; 18:67-77. PubMed
  • Sattler M, Salgia R. Role of the adapter protein CRKL in signal transduction of normal hematopoietic and BCR/ABL-transformed cells. Leukemia 1998; 12:637-44. PubMed
  • Sattler M, Salgia R, Shrikhande G, Verma S, Choi JL, Rohrschneider LR, Griffin JD. The phosphatidylinositol polyphosphate 5-phosphatase SHIP and the protein tyrosine phosphatase SHP-2 form a complex in hematopoietic cells which can be regulated by BCR/ABL and growth factors. Oncogene 1997; 15:2379-84. PubMed
  • Salgia R, Li JL, Ewaniuk DS, Pear W, Pisick E, Burky SA, Ernst T, Sattler M, Chen LB, Griffin JD. BCR/ABL induces multiple abnormalities of cytoskeletal function. J Clin Invest 1997; 100:46-57. PubMed
  • Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF, Golemis EA, Griffin JD. Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1). J Biol Chem 1997; 272:14320-6. PubMed
  • Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD. Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL). J Biol Chem 1997; 272:10248-53. PubMed
  • Sattler M, Salgia R, Durstin MA, Prasad KV, Griffin JD. Thrombopoietin induces activation of the phosphatidylinositol-3' kinase pathway and formation of a complex containing p85PI3K and the protooncoprotein p120CBL. J Cell Physiol 1997; 171:28-33. PubMed
  • Uemura N, Salgia R, Li JL, Pisick E, Sattler M, Griffin JD. The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins. Leukemia 1997; 11:376-85. PubMed
  • Sattler M, Salgia R. Activation of hematopoietic growth factor signal transduction pathways by the human oncogene BCR/ABL. Cytokine Growth Factor Rev 1997; 8:63-79. PubMed
  • Salgia R, Avraham S, Pisick E, Li JL, Raja S, Greenfield EA, Sattler M, Avraham H, Griffin JD. The related adhesion focal tyrosine kinase forms a complex with paxillin in hematopoietic cells. J Biol Chem 1996; 271:31222-6. PubMed
  • Salgia R, Pisick E, Sattler M, Li JL, Uemura N, Wong WK, Burky SA, Hirai H, Chen LB, Griffin JD. p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene. J Biol Chem 1996; 271:25198-203. PubMed
  • Sattler M, Salgia R, Okuda K, Uemura N, Durstin MA, Pisick E, Xu G, Li JL, Prasad KV, Griffin JD. The proto-oncogene product p120CBL and the adaptor proteins CRKL and c-CRK link c-ABL, p190BCR/ABL and p210BCR/ABL to the phosphatidylinositol-3' kinase pathway. Oncogene 1996; 12:839-46. PubMed
  • Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M, de Jong R, Druker B, Heisterkamp N, Chen LB. CRKL links p210BCR/ABL with paxillin in chronic myelogenous leukemia cells. J Biol Chem 1995; 270:29145-50. PubMed
  • Sattler M, Durstin MA, Frank DA, Okuda K, Kaushansky K, Salgia R, Griffin JD. The thrombopoietin receptor c-MPL activates JAK2 and TYK2 tyrosine kinases. Exp Hematol 1995; 23:1040-8. PubMed
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