![]() |
|||||||
![]() |
![]() |
![]() |
![]() |
||||
![]() |
Home | Intranet | Site Map | Search | ||||||
|
Massachusetts Institute of Technology, 1996, Ph.D.
Work in our laboratory is focused on understanding how the function of cell surface receptors is regulated to control cell interactions with each other and with extracellular matrix. In particular, we are interested in how different members of the integrin family of matrix receptors are able to transduce different signals into different cell behaviors. Integrins are heterodimers, with one alpha and one beta subunit. The beta subunit is the primary signaling subunit, yet different integrins that all share a common beta subunit may still mediate different levels of cell motility. To understand the basis of this functional diversity, we are studying integrin-interacting proteins, members of the tetraspanin family, that selectively associate with specific alpha integrin subunits. Using RNA interference and rescue technology, together with time-lapse video microscopy and protein biochemistry, we are exploring the mechanisms by which tetraspanin proteins regulate integrin function at the single cell level. Key findings from these studies guide the design of in vivo experiments to test the role of specific integrin tetraspanin complexes in tumor formation and metastatic colonization. In a second major project, we are studying how tetraspanin proteins regulate integrin-dependent signaling events that influence the function of cadherin cell-cell adhesion proteins. Here again, different integrins may differentially influence cadherin function, and this may depend upon tetraspanin interactions. Longer term goals include determining the functions of other proteins known to be present in integrin-tetraspanin complexes. For example, we have identified specific G protein coupled receptors and Ig superfamily proteins as components of integrin-tetraspanin complexes. Determining how these proteins work together with integrins to control cell motility and cell-cell interactions may yield fresh insights into the process of tumor cell metastasis.
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. 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. Stipp CS, Kolesnikova TV, Hemler ME. EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5. J Cell Biol. 2003 Dec 8;163(5):1167-77.
|
|||||||||||||||