Martin E. Hemler, PhD
Office phone: 617-632-3410
Preferred contact method: email
Area of ResearchMechanisms of Cell Adhesion, Migration, and Invasion
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
BiographyDr. Hemler received his PhD in biological chemistry from the University of Michigan in 1978. After postdoctoral research at DFCI from 1979 to 1984, he received a faculty appointment at DFCI and was promoted to professor in 1994. He is exclusively involved in basic laboratory research, focusing on cell surface molecules that participate in cell adhesion, migration, and invasion.
ResearchMechanisms of Cell Adhesion, Migration, and Invasion
As tumor cells progress to a cancerous state, they may begin to invade surrounding tissue and metastasize to distant sites. These invasion and metastasis processes are highly dependent on cancer cell surface molecules that participate in cell adhesion. A major focus of our laboratory is on a family of adhesion molecules called integrins. For several years, we have sought to determine mechanisms whereby integrin functions can be rapidly turned on and off. Such information is fundamental to our understanding of how cell adhesion, mediated by members of the integrin family, can control cell movement, growth factor responses, gene induction, and tumor growth and metastasis.
More recently, we have been studying certain key integrins as they form highly specific complexes with cell surface "adapter" tetraspanin proteins, a family of proteins having four transmembrane domains. Remarkably, these tetraspanin proteins act as transmembrane linker molecules that link integrin extracellular domains with intracellular signaling enzymes (such as protein kinase C and phosphatidylinositol 4-kinase). We hypothesize that disruption of these complexes will dramatically affect tumor cell migration, invasion, and metastasis.
In addition, we are studying mechanisms whereby cell adhesion and migration are regulated in parallel with the proteolytic degradation of tissue and extracellular matrix proteins that surround tumor cells. We hypothesize that specific cell surface complexes between integrins and molecules that regulate protein degradation are responsible for this coordinated regulation. By various molecular and genetic approaches, we seek to disrupt these complexes.
General approaches used in our laboratory include a monoclonal antibody technique developed for identifying integrin-associated proteins. This experimental approach continues to open up exciting new research directions. We also make use of an extensive array of previously generated integrin mutants as well as cell migration, videomicroscopy, cell adhesion, phosphatidylinositide kinase, and immunofluorescent microscopy assays. In addition, we are currently breeding knockout mice lacking key tetraspanin proteins and testing these mice in various in vivo tumor models.
- Xu D, Hemler ME. Metabolic activation-related CD147-CD98 complex. Mol Cell Proteomics 2005;4:1061-71.
- 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; 281:12976-12985.
- Takeda Y, Kazarov AR, Butterfield CE, Hopkins BD, Benjamin LE, Kaipainen A, Hemler ME. Deletion of tetraspanin CD151 results in decreased pathological angiogenesis in vivo and in vitro. Blood 2007; 109:1524-32.
- Kovalenko OV, Yang XH, Hemler ME. A novel cysteine crosslinking method reveals a direct association between claudin-1 and tetraspanin CD9. Mol Cell Proteomics. 2007; 6: 1855-1867.
- 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 α6 integrin functions, signaling, and molecular organization. Cancer Research. 2008; 68:3204-3213.
- Sharma C, Yang XH, Hemler ME. DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 and CD151. Mol Biol Cell. 2008; 19:3415-3425.
- Kolesnikova TV, Kazarov AR, Lemieux M, Lafleur MA, Kesari S, Kung AL, Hemler ME. Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo. Neoplasia. 2009. 11:77-86.
- Lafleur MA, Xu D, Hemler, ME. Tetraspanin proteins regulate membrane type-1 matrix metalloproteinase (MT1-MMP)-dependent pericellular proteolysis. Mol Biol Cell. 2009; 20:2030-40.
- Xu D, Sharma C, Hemler ME. Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein. FASEB Journal. 2009; 23:3674-81.
- Yang XH, Flores LM, Li Q, Zhou P, Krop IE, Hemler ME. Disruption of laminin-integrin-CD151-FAK Axis sensitizes breast cancer cells to ErbB2 antagonists. Cancer Research. 2010; (accepted for publication).
- Sharma, Chandan, PhD
- Li, Qinglin, Ph.D.
- Knoblich, Konstantin, Ph.D.
- Wang, Hong-Xing, Ph.D.