Work in the Stipp laboratory is focused on understanding how cell surface receptors are regulated to control cells-cell and cell-matrix interactions. In particular, Dr. Stipp's group is interested in how different members of the integrin family of matrix receptors transduce a variety of signals to generate distinct cell behaviors. Integrins are heterodimers of an alpha and a beta subunit, and although the beta subunit is the primary signaling component, pairing of a particular beta integrin with different alpha integrins can mediate different levels of cell motility. To understand the basis of this functional diversity, Dr. Stipp's group is studying members of the tetraspanin family¡Vintegrin-interacting proteins that selectively associate with specific alpha integrin subunits. Using RNA interference and genetic rescue approaches, together with time-lapse video microscopy and protein biochemistry, the group is exploring the mechanisms whereby tetraspanins regulate integrin function, at the single-cell level. Long-term goals include the development of gene therapy strategies for improving the performance of neurons upon therapeutic engraftment into the brain by manipulating the repertoire of integrin extracellular matrix receptors present on neuronal cells, which improves survival and process outgrowth.
Selected Publications:
Stipp CS, Kolesnikova TV, Hemler ME. EWI-2 regulates ?Ñ3?Ò1 integrin-dependent cell functions on laminin-5. J Cell Biol. 2003 Dec 8;163(5):1167-77.
Little KD, Hemler ME, Stipp CS. Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell. 2004 May;15(5):2375-87.
Winterwood NE, Varzavand A, Meland MN, Ashman LK, Stipp CS. A critical role for tetraspanin CD151 in alpha3beta1 and alpha6beta4 integrin-dependent tumor cell functions on laminin-5. Mol Biol Cell. 2006 Jun;17(6):2707-21.
Meland MN, Herndon ME, Stipp CS. Expression of alpha5 integrin rescues fibronectin responsiveness in NT2N CNS neuronal cells. J Neurosci Res. 2009 Jul 13. [Epub ahead of print] (http://www3.interscience.wiley.com/journal/122511711/abstract)
Johnson JL, Winterwood N, Demali KA, Stipp CS. Tetraspanin CD151 regulates RhoA activation and the dynamic stability of carcinoma cell-cell contacts. J Cell Sci. 2009 Jul 1;122(Pt 13):2263-73. Epub 2009 Jun 9. (http://jcs.biologists.org/cgi/content/full/122/13/226
