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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  • Mirzapoiazova T, Pozhitkov A, Nam A, Mambetsariev I, Nelson MS, Tan YC, Zhang K, Raz D, Singhal S, Nasser MW, Kulkarni P, Batra SK, Sattler M, Salgia R. Effects of selected deubiquitinating enzyme inhibitors on the proliferation and motility of lung cancer and mesothelioma cell lines. Int J Oncol 2020. PubMed
  • Weisberg E, Meng C, Case AE, Tiv HL, Gokhale PC, Buhrlage SJ, Yang J, Liu X, Wang J, Gray N, Adamia S, Sattler M, Stone R, Griffin JD. Effects of the multi-kinase inhibitor midostaurin in combination with chemotherapy in models of acute myeloid leukaemia. J Cell Mol Med 2020; 24:2968-2980. PubMed
  • Yang J, Meng C, Weisberg E, Case A, Lamberto I, Magin RS, Adamia S, Wang J, Gray N, Liu S, Stone R, Sattler M, Buhrlage S, Griffin JD. Inhibition of the deubiquitinase USP10 induces degradation of SYK. Br J Cancer 2020. PubMed
  • Weisberg E, Meng C, Case AE, Tiv HL, Gokhale PC, Toure AA, Buhrlage S, Liu X, Wang J, Gray N, Stone R, Adamia S, Winer E, Sattler M, Griffin JD. The combination of FLT3 and SYK kinase inhibitors is toxic to leukaemia cells with CBL mutations. J Cell Mol Med 2020; 24:2145-2156. PubMed
  • Kalvala A, Wallet P, Yang L, Wang C, Li H, Nam A, Nathan A, Mambetsariev I, Poroyko V, Gao H, Chu P, Sattler M, Bild A, Manuel ER, Lee PP, Jolly MK, Kulkarni P, Salgia R. Phenotypic Switching of Naïve T Cells to Immune-Suppressive Treg-Like Cells by Mutant KRAS. J Clin Med 2019. PubMed
  • Tan YC, Srivastava S, Won BM, Kanteti R, Arif Q, Husain AN, Li H, Vigneswaran WT, Pang KM, Kulkarni P, Sattler M, Vaidehi N, Mambetsariev I, Kindler HL, Wheeler DL, Salgia R. EPHA2 mutations with oncogenic characteristics in squamous cell lung cancer and malignant pleural mesothelioma. Oncogenesis 2019; 8:49. PubMed
  • Weisberg E, Meng C, Case A, Sattler M, Tiv HL, Gokhale PC, Buhrlage S, Wang J, Gray N, Stone R, Liu S, Bhagwat SV, Tiu RV, Adamia S, Griffin JD. Evaluation of ERK as a therapeutic target in acute myelogenous leukemia. Leukemia 2019. PubMed
  • Weisberg E, Meng C, Case AE, Sattler M, Tiv HL, Gokhale PC, Buhrlage SJ, Liu X, Yang J, Wang J, Gray N, Stone RM, Adamia S, Dubreuil P, Letard S, Griffin JD. Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies. British Journal of Haematology 2019. PubMed
  • Vallet S, Fan F, Malvestiti S, Pecherstorfer M, Sattler M, Schneeweiss A, Schulze-Bergkamen H, Opferman JT, Cardone MH, Jäger D, Podar K. Rationally derived drug combinations with the novel Mcl-1 inhibitor EU-5346 in breast cancer. Breast Cancer Res Treat 2018. PubMed
  • Salgia R, Mambetsariev I, Hewelt B, Achuthan S, Li H, Poroyko V, Wang Y, Sattler M. Modeling small cell lung cancer (SCLC) biology through deterministic and stochastic mathematical models. 2018; 9:26226-26242. PubMed
  • Weisberg E, Sattler M, Manley PW, Griffin JD. Spotlight on midostaurin in the treatment of FLT3-mutated acute myeloid leukemia and systemic mastocytosis: design, development, and potential place in therapy. Onco Targets Ther 2018; 11:175-182. PubMed
  • Weisberg EL, Sattler M, Azab AK, Eulberg D, Kruschinski A, Manley PW, Stone R, Griffin JD. Inhibition of SDF-1-induced migration of oncogene-driven myeloid leukemia by the L-RNA aptamer (Spiegelmer), NOX-A12, and potentiation of tyrosine kinase inhibition. 2018; 8:109973-109984. PubMed
  • Weisberg EL, Schauer NJ, Yang J, Lamberto I, Doherty L, Bhatt S, Nonami A, Meng C, Letai A, Wright R, Tiv H, Gokhale PC, Ritorto MS, De Cesare V, Trost M, Christodoulou A, Christie A, Weinstock DM, Adamia S, Stone R, Chauhan D, Anderson KC, Seo HS, Dhe-Paganon S, Sattler M, Gray NS, Griffin JD, Buhrlage SJ. Inhibition of USP10 induces degradation of oncogenic FLT3. Nat Chem Biol 2017. PubMed
  • Bhanot H, Weisberg EL, Reddy MM, Nonami A, Neuberg D, Stone RM, Podar K, Salgia R, Griffin JD, Sattler M. Acute myeloid leukemia cells require 6-phosphogluconate dehydrogenase for cell growth and NADPH-dependent metabolic reprogramming. 2017; 8:67639-67650. PubMed
  • Weisberg EL, Puissant A, Stone R, Sattler M, Buhrlage SJ, Yang J, Manley PW, Meng C, Buonopane M, Daley JF, Lazo S, Wright R, Weinstock DM, Christie AL, Stegmaier K, Griffin JD. Characterization of midostaurin as a dual inhibitor of FLT3 and SYK and potentiation of FLT3 inhibition against FLT3-ITD-driven leukemia harboring activated SYK kinase. 2017; 8:52026-52044. PubMed
  • Sattler M, Salgia R. MET in the Driver's Seat: Exon 14 Skipping Mutations as Actionable Targets in Lung Cancer. J Thorac Oncol 2016; 11:1381-3. PubMed
  • Lennon FE, Cianci GC, Kanteti R, Riehm JJ, Arif Q, Poroyko VA, Lupovitch E, Vigneswaran W, Husain A, Chen P, Liao JK, Sattler M, Kindler HL, Salgia R. Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma. Sci Rep 2016; 6:24578. PubMed
  • Bashari MH, Fan F, Vallet S, Sattler M, Arn M, Luckner-Minden C, Schulze-Bergkamen H, Zörnig I, Marme F, Schneeweiss A, Cardone MH, Opferman JT, Jäger D, Podar K. Mcl-1 confers protection of Her2-positive breast cancer cells to hypoxia: therapeutic implications. Breast Cancer Res 2016; 18:26. PubMed
  • Weisberg E, Halilovic E, Cooke VG, Nonami A, Ren T, Sanda T, Simkin I, Yuan J, Antonakos B, Barys L, Ito M, Stone R, Galinsky I, Cowens K, Nelson E, Sattler M, Jeay S, Wuerthner JU, McDonough SM, Wiesmann M, Griffin JD. Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2 Inhibitor CGM097. Mol Cancer Ther 2015; 14:2249-59. PubMed
  • 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 pharmacologic 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, Barilà D, Zhang J, Tai YT, Yasui H, Raje N, Depinho RA, Hideshima T, Chauhan D, Anderson KC. 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
  • Sattler M, Walz C, Crowley BJ, Lengfelder E, Jänne PA, Rogers AM, Kuang Y, Distel RJ, Reiter A, Griffin JD. A sensitive high-throughput method to detect activating mutations of Jak2 in peripheral-blood samples. Blood 2006; 107:1237-8. 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
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