Photo of Andrea I. McClatchey,  PhD

Andrea I. McClatchey, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-5648
Fax: (617) 726-7808

Andrea I. McClatchey, PhD

Massachusetts General Hospital


  • Professor, Pathology, Harvard Medical School



  • Member, Center Scientific Council

Research Abstract

My laboratory is interested in the role of the cytoskeleton:membrane interface in cancer development and progression. To that end we have focused on the Nf2 tumor suppressor and its family members, ezrin, radixin and moesin (the ERM proteins) which localize to the cytoskeleton:membrane interface. The study of Nf2 function in the mouse has revealed tumorigenic and metastatic consequences upon it's loss. The function of the ERM proteins has recently been linked to that of the Ras-related Rho-GTPase which functions in cytoskeletal reorganization and in regulating several well studied molecular signaling pathways. The study of Nf2 function in wild-type cells and the analysis of Nf2-mutant cells derived from these mice has allowed us to link the function of the Nf2 protein (dubbed merlin) to signaling via the Rho family member Rac. This is particularly intriguing given the established relationship between Rac function and cell motility and metastasis. Our efforts are focused on better delineating the molecular function of Nf2 utilizing cell culture and in vitro systems, and utilizing this information to molecularly dissect Nf2-associated tumorigenesis and metastasis in vivo.


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  • Fitamant J, Kottakis F, Benhamouche S, Tian HS, Chuvin N, Parachoniak CA, Nagle JM, Perera RM, Lapouge M, Deshpande V, Zhu AX, Lai A, Min B, Hoshida Y, Avruch J, Sia D, CampreciĆ³s G, McClatchey AI, Llovet JM, Morrissey D, Raj L, Bardeesy N. YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression. Cell Rep 2015. PubMed
  • Plotkin SR, Albers AC, Babovic-Vuksanovic D, Blakeley JO, Breakefield XO, Dunn CM, Evans DG, Fisher MJ, Friedman JM, Giovannini M, Gutmann DH, Kalamarides M, McClatchey AI, Messiaen L, Morrison H, Parkinson DB, Stemmer-Rachamimov AO, Van Raamsdonk CD, Riccardi VM, Rosser T, Schindeler A, Smith MJ, Stevenson DA, Ullrich NJ, van der Vaart T, Weiss B, Widemann BC, Zhu Y, Bakker AC, Lloyd AC. Update from the 2013 international neurofibromatosis conference. Am J Med Genet A 2014. PubMed
  • McClatchey AI. ERM proteins at a glance. J Cell Sci 2014; 127:3199-204. PubMed
  • Shapiro IM, Kolev VN, Vidal CM, Kadariya Y, Ring JE, Wright Q, Weaver DT, Menges C, Padval M, McClatchey AI, Xu Q, Testa JR, Pachter JA. Merlin Deficiency Predicts FAK Inhibitor Sensitivity: A Synthetic Lethal Relationship. Sci Transl Med 2014; 6:237ra68. PubMed
  • Widemann BC, Acosta MT, Ammoun S, Belzberg AJ, Bernards A, Blakeley J, Bretscher A, Cichowski K, Clapp DW, Dombi E, Evans GD, Ferner R, Fernandez-Valle C, Fisher MJ, Giovannini M, Gutmann DH, Hanemann CO, Hennigan R, Huson S, Ingram D, Kissil J, Korf BR, Legius E, Packer RJ, McClatchey AI, McCormick F, North K, Pehrsson M, Plotkin SR, Ramesh V, Ratner N, Schirmer S, Sherman L, Schorry E, Stevenson D, Stewart DR, Ullrich N, Bakker AC, Morrison H. CTF meeting 2012: Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies. Am J Med Genet A 2014; 164A:563-78. PubMed
  • Pore D, Parameswaran N, Matsui K, Stone MB, Saotome I, McClatchey AI, Veatch SL, Gupta N. Ezrin tunes the magnitude of humoral immunity. J Immunol 2013; 191:4048-58. PubMed
  • McClatchey AI, Yap AS. Contact inhibition (of proliferation) redux. Curr Opin Cell Biol 2012; 24:685-94. PubMed
  • McClatchey AI. ERM proteins. Curr Biol 2012; 22:R784-5. PubMed
  • McClatchey AI, Cichowski K. SPRED proteins provide a NF-ty link to Ras suppression. Genes Dev 2012; 26:1515-9. PubMed
  • Gladden AB, Hebert AM, Schneeberger EE, McClatchey AI. The NF2 tumor suppressor, Merlin, regulates epidermal development through the establishment of a junctional polarity complex. Dev Cell 2010; 19:727-39. PubMed
  • Benhamouche S, Curto M, Saotome I, Gladden AB, Liu CH, Giovannini M, McClatchey AI. Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev 2010; 24:1718-30. PubMed
  • Wong HK, Lahdenranta J, Kamoun WS, Chan AW, McClatchey AI, Plotkin SR, Jain RK, di Tomaso E. Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. Cancer Res 2010; 70:3483-93. PubMed
  • Fehon RG, McClatchey AI, Bretscher A. Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol 2010; 11:276-87. PubMed
  • Shaffer MH, Huang Y, Corbo E, Wu GF, Velez M, Choi JK, Saotome I, Cannon JL, McClatchey AI, Sperling AI, Maltzman JS, Oliver PM, Bhandoola A, Laufer TM, Burkhardt JK. Ezrin is highly expressed in early thymocytes, but dispensable for T cell development in mice. PLoS ONE 2010; 5:e12404. PubMed
  • Morris ZS,McClatchey AI. Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma. Proc Natl Acad Sci U S A 2009; 106:9767-72. PubMed
  • Morris ZS,McClatchey AI. The neurofibroma cell of origin: SKPs expand the playing field. Cell Stem Cell 2009; 4:371-2. PubMed
  • McClatchey AI,Fehon RG. Merlin and the ERM proteins--regulators of receptor distribution and signaling at the cell cortex. Trends Cell Biol 2009; 19:198-206. PubMed
  • Shaffer MH,Dupree RS,Zhu P,Saotome I,Schmidt RF,McClatchey AI,Freedman BD,Burkhardt JK. Ezrin and moesin function together to promote T cell activation. J Immunol 2009; 182:1021-32. PubMed
  • Larsson J,Ohishi M,Garrison B,Aspling M,Janzen V,Adams GB,Curto M,McClatchey AI,Schipani E,Scadden DT. Nf2/merlin regulates hematopoietic stem cell behavior by altering microenvironmental architecture. Cell Stem Cell 2008; 3:221-7. PubMed
  • Plotkin SR,Singh MA,O'Donnell CC,Harris GJ,McClatchey AI,Halpin C. Audiologic and radiographic response of NF2-related vestibular schwannoma to erlotinib therapy. Nat Clin Pract Oncol 2008; 5:487-91. PubMed
  • Kim WJ, Okimoto RA, Purton LE, Goodwin M, Haserlat SM, Dayyani F, Sweetser DA, McClatchey AI, Bernard OA, Look AT, Bell DW, Scadden DT, Haber DA. Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias. Blood 2008; 111:4716-22. PubMed
  • Cole BK, Curto M, Chan AW, McClatchey AI. Localization to the cortical cytoskeleton is necessary for Nf2/merlin-dependent epidermal growth factor receptor silencing. Mol Cell Biol 2007; 28:1274-84. PubMed
  • Curto M, McClatchey AI. Nf2/Merlin: a coordinator of receptor signalling and intercellular contact. Br J Cancer 2007; 98:256-62. PubMed
  • Johannessen CM, Johnson BW, Williams SM, Chan AW, Reczek EE, Lynch RC, Rioth MJ, McClatchey A, Ryeom S, Cichowski K. TORC1 is essential for NF1-associated malignancies. Curr Biol 2008; 18:56-62. PubMed
  • Curto M, Cole BK, Lallemand D, Liu CH, McClatchey AI. Contact-dependent inhibition of EGFR signaling by Nf2/Merlin. J Cell Biol 2007; 177:893-903. PubMed
  • Bonilha VL, Rayborn ME, Saotome I, McClatchey AI, Hollyfield JG. Microvilli defects in retinas of ezrin knockout mice. Exp Eye Res 2005; 82:720-9. PubMed
  • Yajnik V, Paulding C, Sordella R, McClatchey AI, Saito M, Wahrer DC, Reynolds P, Bell DW, Lake R, van den Heuvel S, Settleman J, Haber DA. DOCK4, a GTPase activator, is disrupted during tumorigenesis. Cell 2003; 112:673-84. PubMed
  • McClatchey AI, Saotome I, Mercer K, Crowley D, Gusella JF, Bronson RT, Jacks T. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev 1998; 12:1121-33. PubMed
  • McClatchey AI, Saotome I, Ramesh V, Gusella JF, Jacks T. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. Genes Dev 1997; 11:1253-65. PubMed
  • McClatchey AI, Lin CS, Wang J, Hoffman EP, Rojas C, Gusella JF. The genomic structure of the human skeletal muscle sodium channel gene. Hum Mol Genet 1992; 1:521-7. PubMed
  • McClatchey AI, McKenna-Yasek D, Cros D, Worthen HG, Kuncl RW, DeSilva SM, Cornblath DR, Gusella JF, Brown RH. Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. Nat Genet 1992; 2:148-52. PubMed
  • McClatchey AI, Trofatter J, McKenna-Yasek D, Raskind W, Bird T, Pericak-Vance M, Gilchrist J, Arahata K, Radosavljevic D, Worthen HG. Dinucleotide repeat polymorphisms at the SCN4A locus suggest allelic heterogeneity of hyperkalemic periodic paralysis and paramyotonia congenita. Am J Hum Genet 1992; 50:896-901. PubMed
  • McClatchey AI, Van den Bergh P, Pericak-Vance MA, Raskind W, Verellen C, McKenna-Yasek D, Rao K, Haines JL, Bird T, Brown RH. Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita. Cell 1992; 68:769-74. PubMed