Other Perelman School of Medicine Affiliations
Biochemistry & Molecular Biophysics Graduate Group

Degrees
B.A., University of Oxford, 1987
M.Phil, Yale University, 1992
Ph.D., Yale University, 1996

Honors
Burroughs Wellcome Fund Career Award in Biomedical Sciences, 2001
Howard Temin Award from National Cancer Institute, 2001
Dennis and Marsha Dammerman Scholar of the Damon Runyon Cancer Research Foundation, 2006

Research Description
We are interested in the stereochemical details of the intermolecular interactions in signal transduction pathways.

1. Ligand induced activation of receptor tyrosine kinases (RTKs). Activation of RTKs lead to a host of downstream signaling events that result in a variety of different cellular responses, including stimulated growth. Inappropriate receptor activation can lead to cancer and understanding how these receptors function is of significant biomedical importance. Recent advances have led to the proposal of a novel mechanism for activation of one RTK that we study, the epidermal growth factor (EGF) receptor. We are investigating the implications of this model for activation and inactivation this and other RTKs.

2. Protein-protein interactions in intracellular signaling. It is clear that formation of large multimolecular assemblies plays a key role in controlling intracellular signaling, trafficking and other processes. We are using a variety of biophysical techniques to study such assembly formation in vitro, and X-ray crystallography to determine the structures of key complexes.

Representative Publications
Li, S., Schmitz, K., Jeffrey, P.D., Wiltzius, J., Kussie, P. and Ferguson, K.M. Structural basis for inhibition of the Epidermal Growth Factor Receptor by cetuximab, Cancer Cell 7:301-311, 2005.

Dawson, J.P., Berger, M.B., Lin, C.-C., Schlessinger, J., Lemmon, M.A. and Ferguson, K.M.: Epidermal growth factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface., Mol. Cell Biol 25:7734-7742, 2005.

Bouyain S., Longo, P.A., Li, S, Ferguson, K.M., Leahy, D.J.: The Extracellular Region of ErbB4 Adopts a Tethered Conformation in the Absence of Ligand, Proc. Natl. Acad. Sci. (USA) 102:15024-15029, 2005.

Ferguson, K.M., Berger, M.B., Mendrola, J.M., Cho, H.S., Leahy, D.J. & Lemmon, M.A. EGF activates its receptor by removing interactions that auto-inhibit ectodomain dimerization, Molecular Cell 11:507-517, 2003.

Burgess, A.W., Cho, H.S., Eigenbrot, C., Ferguson, K.M., Garrett, T.P.J., Leahy, D.J., Lemmon, M.A., Sliwkowski, M.X., Ward, C.W., & Yokoyama, S. An Open-and-Shut Case? Recent Insights into the Activation of EGF/ErbB Receptors, Molecular Cell 12:541-552, 2003.

Click here for a full list of publications
(searches the National Library of Medicine's PubMed database.)