Photo of Margaret A. Shipp,   M.D.

Margaret A. Shipp, M.D.

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3874
Fax: (617) 632-4734


margaret_shipp@dfci.harvard.edu

Margaret A. Shipp, M.D.

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Director, Lymphoma Program, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Member, Center Scientific Council

Research Abstract

My laboratory and clinical interests are primarily in the area of aggressive B-cell non-Hodgkin's lymphomas. In the laboratory, we are attempting to identify cellular and molecular features which contribute to the unique natural histories of clinically relevant subsets of patients with aggressive B-cell lymphomas. These laboratory-based initiatives are closely integrated with longstanding clinical efforts to identify and treat subsets of patients whose aggressive B-cell lymphomas have very different natural histories. Another major area of emphasis in the laboratory is the interaction between tumor cells and surrounding stroma and the development of a conducive tumor microenvironment. We have developed in vitro models to analyze the events associated with the interaction between epithelial carcinoma cells and stromal elements and have begun to develop similar informative in vitro models for the interaction between aggressive B-cell lymphomas and relevant stromal components.

Publications

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  • 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
  • Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H, Connelly CF, Sun HH, Daadi SE, Freeman GJ, Armand P, Chapuy B, de Jong D, Hoppe RT, Neuberg DS, Rodig SJ, Shipp MA. PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. J Clin Oncol 2016. PubMed
  • Howitt BE, Sun HH, Roemer MG, Kelley A, Chapuy B, Aviki E, Pak C, Connelly C, Gjini E, Shi Y, Lee L, Viswanathan A, Horowitz N, Neuberg D, Crum CP, Lindeman NL, Kuo F, Ligon AH, Freeman GJ, Hodi FS, Shipp MA, Rodig SJ. Genetic Basis for PD-L1 Expression in Squamous Cell Carcinomas of the Cervix and Vulva. JAMA Oncol 2016; 2:518-22. PubMed
  • Chapuy B, Roemer MG, Stewart C, Tan Y, Abo RP, Zhang L, Dunford AJ, Meredith DM, Thorner AR, Jordanova ES, Liu G, Feuerhake F, Ducar MD, Illerhaus G, Gusenleitner D, Linden EA, Sun HH, Homer H, Aono M, Pinkus GS, Ligon AH, Ligon KL, Ferry JA, Freeman GJ, van Hummelen P, Golub TR, Getz G, Rodig SJ, de Jong D, Monti S, Shipp MA. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood 2016; 127:869-81. PubMed
  • Chapuy B, Cheng H, Watahiki A, Ducar MD, Tan Y, Chen L, Roemer MG, Ouyang J, Christie AL, Zhang L, Gusenleitner D, Abo RP, Farinha P, von Bonin F, Thorner AR, Sun HH, Gascoyne RD, Pinkus GS, van Hummelen P, Wulf GG, Aster JC, Weinstock DM, Monti S, Rodig SJ, Wang Y, Shipp MA. Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biologic heterogeneity of the disease. Blood 2016. PubMed
  • Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Léopold V, Sjoberg M, Keane TM, Verma A, Ala U, Tay Y, Wu D, Seitzer N, Velasco-Herrera Mdel C, Bothmer A, Fung J, Langellotto F, Rodig SJ, Elemento O, Shipp MA, Adams DJ, Chiarle R, Pandolfi PP. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell 2015. PubMed
  • Weinstock DM, Dalla-Favera R, Gascoyne RD, Leonard JP, Levy R, Lossos IS, Melnick AM, Nowakowski GS, Press OW, Savage KJ, Shipp MA, Staudt LM. A roadmap for discovery and translation in lymphoma. Blood 2015; 125:2175-7. PubMed
  • Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015; 372:311-9. PubMed
  • Carey CD, Gusenleitner D, Chapuy B, Kovach AE, Kluk MJ, Sun HH, Crossland RE, Bacon CM, Rand V, Dal Cin P, Le LP, Neuberg D, Sohani AR, Shipp MA, Monti S, Rodig SJ. Molecular classification of MYC-driven B-cell lymphomas by targeted gene expression profiling of fixed biopsy specimens. J Mol Diagn 2014; 17:19-30. PubMed
  • Shi M, Roemer MG, Chapuy B, Liao X, Sun H, Pinkus GS, Shipp MA, Freeman GJ, Rodig SJ. Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain. Am J Surg Pathol 2014. PubMed
  • Hao Y, Chapuy B, Monti S, Sun HH, Rodig SJ, Shipp MA. Selective JAK2 inhibition specifically decreases Hodgkin lymphoma and mediastinal large B-cell lymphoma growth in vitro and in vivo. Clin Cancer Res 2014. PubMed
  • Croci DO, Cerliani JP, Dalotto-Moreno T, Méndez-Huergo SP, Mascanfroni ID, Dergan-Dylon S, Toscano MA, Caramelo JJ, García-Vallejo JJ, Ouyang J, Mesri EA, Junttila MR, Bais C, Shipp MA, Salatino M, Rabinovich GA. Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. Cell 2014; 156:744-58. PubMed
  • Chapuy B, McKeown MR, Lin CY, Monti S, Roemer MG, Qi J, Rahl PB, Sun HH, Yeda KT, Doench JG, Reichert E, Kung AL, Rodig SJ, Young RA, Shipp MA, Bradner JE. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell 2013; 24:777-90. PubMed
  • Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, Yu H, Fletcher CD, Freeman GJ, Shipp MA, Rodig SJ. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res 2013; 19:3462-73. PubMed
  • Chen L, Monti S, Juszczynski P, Ouyang J, Chapuy B, Neuberg D, Doench JG, Bogusz AM, Habermann TM, Dogan A, Witzig TE, Kutok JL, Rodig SJ, Golub T, Shipp MA. SYK inhibition modulates distinct PI3K/AKT- dependent survival pathways and cholesterol biosynthesis in diffuse large B cell lymphomas. Cancer Cell 2013; 23:826-38. PubMed
  • Ouyang J, Plütschow A, Pogge von Strandmann E, Reiners KS, Ponader S, Rabinovich GA, Neuberg D, Engert A, Shipp MA. Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma. Blood 2013; 121:3431-3. PubMed
  • Yan Q, Xu R, Zhu L, Cheng X, Wang Z, Manis J, Shipp MA. BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation, ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and RNF8. Mol Cell Biol 2013; 33:845-57. PubMed
  • Laderach DJ, Gentilini LD, Giribaldi L, Delgado VC, Nugnes L, Croci DO, Al Nakouzi N, Sacca P, Casas G, Mazza O, Shipp MA, Vazquez E, Chauchereau A, Kutok JL, Rodig SJ, Elola MT, Compagno D, Rabinovich GA. A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease. Cancer Res 2013. PubMed
  • Croci DO, Salatino M, Rubinstein N, Cerliani JP, Cavallin LE, Leung HJ, Ouyang J, Ilarregui JM, Toscano MA, Domaica CI, Croci MC, Shipp MA, Mesri EA, Albini A, Rabinovich GA. Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi's sarcoma. J Exp Med 2012; 209:1985-2000. PubMed
  • Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B, Ficarro SB, Polak K, Tondera D, Gounarides J, Yin H, Zhou F, Green MR, Chen L, Monti S, Marto JA, Shipp MA, Danial NN. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 2012; 22:547-60. PubMed
  • Monti S, Chapuy B, Takeyama K, Rodig SJ, Hao Y, Yeda KT, Inguilizian H, Mermel C, Currie T, Dogan A, Kutok JL, Beroukhim R, Neuberg D, Habermann TM, Getz G, Kung AL, Golub TR, Shipp MA. Integrative analysis reveals an outcome-associated and targetable pattern of p53 and cell cycle deregulation in diffuse large B cell lymphoma. Cancer Cell 2012; 22:359-72. PubMed
  • Ouyang J, Juszczynski P, Rodig SJ, Green MR, O'Donnell E, Currie T, Armant M, Takeyama K, Monti S, Rabinovich GA, Ritz J, Kutok JL, Shipp MA. Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders. Blood 2011. PubMed
  • Green MR, Monti S, Dalla-Favera R, Pasqualucci L, Walsh NC, Schmidt-Supprian M, Kutok JL, Rodig SJ, Neuberg DS, Rajewsky K, Golub TR, Alt FW, Shipp MA, Manis JP. Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program. Proc Natl Acad Sci U S A 2011; 108:2873-8. PubMed
  • Rodig SJ, Kutok JL, Paterson JC, Nitta H, Zhang W, Chapuy B, Tumwine LK, Montes-Moreno S, Agostinelli C, Johnson NA, Ben-Neriah S, Farinha P, Shipp MA, Piris MA, Grogan TM, Pileri SA, Gascoyne RD, Marafioti T. The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker to identify c-MYC translocated lymphomas. Haematologica 2010; 95:2056-62. PubMed
  • Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O'Donnell E, Chapuy B, Takeyama K, Neuberg D, Golub TR, Kutok JL, Shipp MA. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 2010; 116:3268-77. PubMed
  • Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, Lacasce A, Schaefer-Cutillo J, De Vos S, Sinha R, Leonard JP, Cripe LD, Gregory SA, Sterba MP, Lowe AM, Levy R, Shipp MA. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non Hodgkin's lymphoma and chronic lymphocytic leukemia. Blood 2010; 115:2578-85. PubMed
  • Juszczynski P, Rodig SJ, Ouyang J, O'Donnell E, Takeyama K, Mlynarski W, Mycko K, Szczepanski T, Gaworczyk A, Krivtsov A, Faber J, Sinha AU, Rabinovich GA, Armstrong SA, Kutok JL, Shipp MA. MLL-rearranged B lymphoblastic leukemias selectively express the immunoregulatory carbohydrate-binding protein galectin-1. Clin Cancer Res 2010; 16:2122-30. PubMed
  • Juszczynski P, Chen L, O'Donnell E, Polo JM, Ranuncolo SM, Dalla-Favera R, Melnick A, Shipp MA. BCL6 modulates tonic BCR signaling in diffuse large B-cell lymphomas by repressing the SYK phosphatase, PTPROt. Blood 2009; 114:5315-21. PubMed
  • Yan Q, Dutt S, Xu R, Graves K, Juszczynski P, Manis JP, Shipp MA. BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Mol Cell 2009; 36:110-20. PubMed
  • Wu D, Dutra B, Lindeman N, Takahashi H, Takeyama K, Harris NL, Pinkus GS, Longtine J, Shipp M, Kutok JL. No evidence for the JAK2 (V617F) or JAK2 exon 12 mutations in primary mediastinal large B-cell lymphoma. Diagn Mol Pathol 2009; 18:144-9. PubMed
  • Abramson JS,Chen W,Juszczynski P,Takahashi H,Neuberg D,Kutok JL,Takeyama K,Shipp MA. The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas. British Journal of Haematology 2008; 144:358-66. PubMed
  • Rodig SJ,Ouyang J,Juszczynski P,Currie T,Law K,Neuberg DS,Rabinovich GA,Shipp MA,Kutok JL. AP1-dependent galectin-1 expression delineates classical hodgkin and anaplastic large cell lymphomas from other lymphoid malignancies with shared molecular features. Clin Cancer Res 2008; 14:3338-44. PubMed
  • Crump SR, Shipp MP, McCray GG, Morris SJ, Okoli JA, Caplan LS, Thorne SL, Blumenthal DS. Abnormal mammogram follow-up: do community lay health advocates make a difference? Health Promot Pract 2008; 9:140-8. PubMed
  • Chen L, Monti S, Juszczynski P, Daley J, Chen W, Witzig TE, Habermann TM, Kutok JL, Shipp MA. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 2007; 111:2230-7. PubMed
  • Takeyama K, Monti S, Manis JP, Cin PD, Getz G, Beroukhim R, Dutt S, Aster JC, Alt FW, Golub TR, Shipp MA. Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas. Oncogene 2008; 27:318-22. PubMed
  • Parekh S, Polo JM, Shaknovich R, Juszczynski P, Lev P, Ranuncolo SM, Yin Y, Klein U, Cattoretti G, Dalla Favera R, Shipp MA, Melnick A. BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms. Blood 2007; 110:2067-74. PubMed
  • Juszczynski P, Ouyang J, Monti S, Rodig SJ, Takeyama K, Abramson J, Chen W, Kutok JL, Rabinovich GA, Shipp MA. The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proc Natl Acad Sci U S A 2007; 104:13134-9. PubMed
  • Deng J, Carlson N, Takeyama K, Dal Cin P, Shipp M, Letai A. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell 2007; 12:171-85. PubMed
  • Peterson BA, Johnson J, Shipp MA, Barcos M, Gockerman JP, Canellos GP, Cancer FT, Leukemia GB. High dose CHOP: A phase II study of initial treatment in aggressive non-Hodgkin lymphoma. Cancer and Leukemia Group B 9351. Leuk Lymphoma 2007; 48:870-80. PubMed
  • Robertson MJ, Kahl BS, Vose JM, de Vos S, Laughlin M, Flynn PJ, Rowland K, Cruz JC, Goldberg SL, Musib L, Darstein C, Enas N, Kutok JL, Aster JC, Neuberg D, Savage KJ, LaCasce A, Thornton D, Slapak CA, Shipp MA. Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2007; 25:1741-6. PubMed
  • Polo JM, Juszczynski P, Monti S, Cerchietti L, Ye K, Greally JM, Shipp M, Melnick A. Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas. Proc Natl Acad Sci U S A 2007; 104:3207-12. PubMed
  • Rodig SJ, Savage KJ, LaCasce AS, Weng AP, Harris NL, Shipp MA, Hsi ED, Gascoyne RD, Kutok JL. Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma. Am J Surg Pathol 2007; 31:106-12. PubMed
  • Rodig SJ, Abramson JS, Pinkus GS, Treon SP, Dorfman DM, Dong HY, Shipp MA, Kutok JL. Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1H). Clin Cancer Res 2006; 12:7174-9. PubMed
  • Chen L, Juszczynski P, Takeyama K, Aguiar RC, Shipp MA. Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation. Blood 2006; 108:3428-33. PubMed
  • Juszczynski P, Kutok JL, Li C, Mitra J, Aguiar RC, Shipp MA. BAL1 and BBAP are regulated by a gamma interferon-responsive bidirectional promoter and are overexpressed in diffuse large B-cell lymphomas with a prominent inflammatory infiltrate. Mol Cell Biol 2006; 26:5348-59. PubMed
  • Takahashi H, Feuerhake F, Kutok JL, Monti S, Dal Cin P, Neuberg D, Aster JC, Shipp MA. FAS death domain deletions and cellular FADD-like interleukin 1beta converting enzyme inhibitory protein (long) overexpression: alternative mechanisms for deregulating the extrinsic apoptotic pathway in diffuse large B-cell lymphoma subtypes. Clin Cancer Res 2006; 12:3265-71. PubMed
  • Pasqualucci L, Compagno M, Houldsworth J, Monti S, Grunn A, Nandula SV, Aster JC, Murty VV, Shipp MA, Dalla-Favera R. Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exp Med 2006; 203:311-7. PubMed
  • Takahashi H, Feuerhake F, Monti S, Kutok JL, Aster JC, Shipp MA. Lack of IKBA coding region mutations in primary mediastinal large B-cell lymphoma and the host response subtype of diffuse large B-cell lymphoma. Blood 2006; 107:844-5. PubMed
  • Yan Q, Dutt S, Xu R, Graves K, Juszczynski P, Manis JP, Shipp MA. BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response Mol Cell 2009.
  • Shipp MA, Aquino SL, Harris NL.. Case Records of the Massachusetts General Hospital: A thirty year-old woman with fever and mediastinal mass. New England Journal of Medicine 2006.
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