Photo of Martin E. Hemler,  PhD

Martin E. Hemler, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3410
Fax: (617) 632-2662


martin_hemler@dfci.harvard.edu

Martin E. Hemler, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Pathology, Harvard Medical School
  • Professor, Cancer Immunology and Virology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

Cell adhesion is a basic process in cell biology, controlling cell growth, death, differentiation, movement, and tissue organization in normal cells, as well as the proliferation and metastasis of tumor cells. My laboratory focuses on the molecular basis for cell adhesion and migration. In particular, we are interested in the structures and functions of heterodimers in the INTEGRIN family. For example, we are studying mechanisms whereby integrin functions are rapidly turned on and off, and different integrins link to distinct cellular signaling pathways. In addition, we study other cell surface transmembrane proteins that associate with integrins. Remarkably, we have recently learned that transmembrane linker proteins, called tetraspanin proteins, allow the membrane proximal extracellular domains of integrins to play key roles in the recruitment of intracellular signaling enzymes such as protein kinase C, and phosphatidylinositol 4-kinase. Also we study how certain integrins may be linked to regulation of matrix metalloproteinase (MMP) production, a key process during cell and tissue remodeling and tumor cell metastasis. Most recently, we have deleted the tetraspanin CD151 gene from mice, and we are using those mice to investigate the role of CD151 during tumor progression.

Publications

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  • Wang HX, Sharma C, Knoblich K, Granter SR, Hemler ME. EWI-2 negatively regulates TGF-β signaling leading to altered melanoma growth and metastasis. Cell Res 2015; 25:370-85. PubMed
  • Knoblich K, Wang HX, Sharma C, Fletcher AL, Turley SJ, Hemler ME. Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation. Cell Mol Life Sci 2014; 71:1305-14. PubMed
  • Deng X, Li Q, Hoff J, Novak M, Yang H, Jin H, Erfani SF, Sharma C, Zhou P, Rabinovitz I, Sonnenberg A, Yi Y, Zhou P, Stipp CS, Kaetzel DM, Hemler ME, Yang XH. Integrin-associated CD151 drives ErbB2-evoked mammary tumor onset and metastasis. Neoplasia 2012; 14:678-89. PubMed
  • Wang HX, Li Q, Sharma C, Knoblich K, Hemler ME. Tetraspanin protein contributions to cancer. Biochem Soc Trans 2011; 39:547-52. PubMed
  • Yang XH, Flores LM, Li Q, Zhou P, Xu F, Krop IE, Hemler ME. Disruption of Laminin-Integrin-CD151-Focal Adhesion Kinase Axis Sensitizes Breast Cancer Cells to ErbB2 Antagonists. Cancer Res 2010; 70:2256-63. PubMed
  • Xu D, Sharma C, Hemler ME. Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein. FASEB J 2009; 23:3674-81. PubMed
  • Lafleur MA,Xu D,Hemler ME. Tetraspanin proteins regulate membrane type-1 matrix metalloproteinase-dependent pericellular proteolysis. Mol Biol Cell 2009; 20:2030-40. PubMed
  • Kolesnikova TV,Kazarov AR,Lemieux ME,Lafleur MA,Kesari S,Kung AL,Hemler ME. Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo. Neoplasia 2008; 11:77-86, 4p following 86. PubMed
  • Fiorentino M,Zadra G,Palescandolo E,Fedele G,Bailey D,Fiore C,Nguyen PL,Migita T,Zamponi R,Di Vizio D,Priolo C,Sharma C,Xie W,Hemler ME,Mucci L,Giovannucci E,Finn S,Loda M. Overexpression of fatty acid synthase is associated with palmitoylation of Wnt1 and cytoplasmic stabilization of beta-catenin in prostate cancer. Lab Invest 2008; 88:1340-8. PubMed
  • Hemler ME. Targeting of tetraspanin proteins--potential benefits and strategies. Nat Rev Drug Discov 2008; 7:747-58. PubMed
  • Sharma C,Yang XH,Hemler ME. DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 and CD151. Mol Biol Cell 2008; 19:3415-25. PubMed
  • Yang XH, Richardson AL, Torres-Arzayus MI, Zhou P, Sharma C, Kazarov AR, Andzelm MM, Strominger JL, Brown M, Hemler ME. CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization. Cancer Res 2008; 68:3204-13. PubMed
  • Kovalenko OV, Yang XH, Hemler ME. A novel cysteine cross-linking method reveals a direct association between claudin-1 and tetraspanin CD9. Mol Cell Proteomics 2007; 6:1855-67. PubMed
  • Takeda Y, Kazarov AR, Butterfield CE, Hopkins BD, Benjamin LE, Kaipainen A, Hemler ME. Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro. Blood 2006; 109:1524-32. PubMed
  • Wunschmann S, Muller HM, Stipp CS, Hemler ME, Stapleton JT. In vitro interaction between hepatitis C virus (HCV) envelope glycoprotein E2 and serum lipoproteins (LPs) results in enhanced cellular binding of both HCV E2 and LPs. J Infect Dis 2006; 194:1058-67. PubMed
  • Yang XH, Kovalenko OV, Kolesnikova TV, Andzelm MM, Rubinstein E, Strominger JL, Hemler ME. Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization. J Biol Chem 2006; 281:12976-85. PubMed
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