Department of Cell Biology
The CBR Center for Biomedical Research, Inc.
Warren Alpert Building, Room 133
200 Longwood Avenue
Boston, MA 02115
Tel: (617) 713-8888
Fax: (617) 713-8898
Web Page: The Kirchhausen Lab Page
8 postdoctoral fellows, 2 graduate students
Our research focuses on the processes that mediate and regulate the movement of membrane proteins throughout cells. In particular we study the molecular mechanisms that underlie the cell's sorting machineries responsible for receptor-mediated endocytosis and for secretion. We also study the question of protein networks; their regulation and signal-integration linking the spatial organization of the cortical cytoskeleton in cell with cell migration and growth, antigen presentation and vesicular traffic.
These efforts led to the first structure determination at atomic resolution of clathrin. We determined the structure of its amino-terminal portion, a region critical for interactions controlling coat assembly and cargo sorting. We continued with this structural approach and determined the mode of interaction of b-arrestins and adaptors with clathrin, determined the atomic structure of a clathrin adaptor, unveiled the basic structure of the triskelion leg and established the way triskelions pack when they form the clathrin coat (http://cbr.med.harvard.edu/investigators/kirchhausen/lab/research.html).
We are currently using biochemical and cell biological approaches to examine how adaptors recognize the membrane receptors that are specifically recruited into a clathrin coated pit, and how HIV Nef activates the endocytosis of the HIV receptor CD4 and of MHC class I; processes that are intimately linked to development of disease.
We recently began focusing on two new research directions for probing mechanisms in vesicular membrane traffic and protein-protein interactions. They involve the development of medium throughput screens to identify chemicals that interfere with membrane traffic and the implementation of live-cell imaging methods to visualize intracellular traffic in real-time.
With these studies we expect to obtain molecular movies, new frameworks for analyzing some of the molecular contacts and switches that participate in the regulation, availability and intracellular traffic of the many molecules involved in signal transduction, immune response, lipid homeostasis and cell-cell recognition.
- Ehrlich, M., Boll, W., Van Oijen, A., Hariharan, R., Chandran, K., Nibert, M. L., and Kirchhausen, T. (2004). Endocytosis by random initiation and stabilization of clathrin-coated pits. Cell 118, 591-605.
- Fotin, A., Cheng, Y., Grigorieff, N., Walz, T., Harrison, S. C., and Kirchhausen, T. (2004). Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating. Nature 432, 649-653.
- Macia, E., Ehrlich, M., Massol, R., Boucrot, E., Brunner, C., and Kirchhausen, T. (2006). Dynasore, a cell permeable inhibitor of dynamin. Developmental Cell (in press).
- Pelish, H. E., Peterson, J. R., Salvarezza, S. B., Rodriguez-Boulan, E., Chen, J. L., Stamnes, M., Macia, E., Feng, Y., Shair, M. D., and Kirchhausen, T. (2006). Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro. Nat Chem Biol 2, 39-46.
BBS webpage updated 12/02/2009