Immunology
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Martin E. Hemler

Department of Pathology
Dana-Farber Cancer Institute
44 Binney Street
Dana Building, Room D-1430
Boston MA 02115
Tel: 617-632-3410
Fax: 617-632-2662
email:Martin_Hemler@dfci.harvard.edu
8 postdoctoral fellows

 Martin E. Hemler

Research in Dr. Hemler's laboratory is focused on a novel type of cell surface microdomain, containing tetraspanin proteins (e.g. CD9, CD63, CD81, CD151) and associated integrins (cell adhesion receptors) and other proteins. These microdomains are involved in the regulation of cell morphology, migration, and signaling. Although these microdomains may contain gangliosides and cholesterol, they are distinct from lipid rafts insofar as being more dense in sucrose gradients, and more dependent on protein-protein interactions. Also, although tetraspanin palmitoylation contributes to the assembly of tetraspanin microdomains, this palmitoylation has little effect on complex density, and it does not promote detergent insolubility. Specific projects are as follows:

  • A mass spectrometry/proteomics approach has led to the identification and characterization of Ig superfamily proteins EWI-2 and EWI-F as major protein partners for CD9 and CD81. It remains to be determined whether these molecules have counter receptors, and whether they influence the multitude of functions that involve CD81 and CD9.
  • The EWI-2 protein, linked via CD81, forms a complex with the a4b1 integrin, thereby modulating leukocyte morphology and motility on the endothelial cell molecule VCAM1. Disruption of this complex is likely to have important implications for leukocyte recruitment during normal and pathological situations. This remains to be explored. 
  • Biochemical rules for specific assembly of tetraspanin complexes need to be elucidated. To achieve this we need to analyze further a) the role of tetraspanin palmitoylation and cholesterol association, b) the role of specific transmembrane domain motifs.
  • An exciting new connection between tetraspanins and chemokine signaling has been uncovered. The functional consequences of this are being actively explored.

 

Papers & Publications:

Xu D, Hemler ME. Metabolic activation-related CD147 – CD98 complex. Mol Cell Proteomics. 2005; 4:1061-1071.

Hemler ME. Functions of tetraspanin-enriched microdomains. Nature Rev. Molec. Cell Biol., 2005; 6:801-811.

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; (in press).