Professor
Developmental Biology
Developmental Biology
Email Website Contact Info More Publications
A central process in development of multicellular organisms is the generation of different cell types. One mechanism involved in this process is based on cell-cell interactions between equivalent cells, leading to inhibition of one fate in a subset of cells. Remarkably, vertebrate homologs of Drosophila Notch have been cloned from many organisms and experimental data suggest that a conserved signal transaction pathway is involved in cell fate ion during vertebrate development as well. We demonstrated that Notch signaling is propagated through release of its intracellular domain, which acts as a nuclear transcription factor. We are interested in how additional signaling pathways participate with Notch in shaping the final developmental outcome. Students joining the lab will be utilizing existing genetic tools (conditional alleles of Notch pathway genes; reporter strains, linage tracing) and developing additional ones to investigate Notch signaling in ed vertebrate tissues.
Research Publications
Huppert SS, Ilagan MX, De Strooper B, Kopan R (2005 May). Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation. Dev Cell. 8 (5): 677-88. Full Article >
Pan Y, Lin MH, Tian X, Cheng HT, Gridley T, Shen J, Kopan R (2004 Nov). gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis. Dev Cell. 7 (5): 731-43. Full Article >
Selkoe D, Kopan R (2003). Notch and Presenilin: regulated intramembrane proteolysis links development and degeneration. Annu Rev Neurosci. 26: 565-97. Full Article >
Schroeter EH, Ilagan MX, Brunkan AL, Hecimovic S, Li YM, Xu M, Lewis HD, Saxena MT, De Strooper B, Coonrod A, Tomita T, Iwatsubo T, Moore CL, Goate A, Wolfe MS, Shearman M, Kopan R (2003 Oct 28). A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis. Proc Natl Acad Sci U S A. 100 (22): 13075-80. Full Article >
Cheng HT, Miner JH, Lin M, Tansey MG, Roth K, Kopan R (2003 Oct). Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney. Development. 130 (20): 5031-42. Full Article >
Mumm JS, Schroeter EH, Saxena MT, Griesemer A, Tian X, Pan DJ, Ray WJ, Kopan R (2000 Feb). A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Mol Cell. 5 (2): 197-206. Full Article >
Contact Info
Raphael Kopan, Ph.D.
Office Location: 3600 Cancer Research Building
Office Phone: 314-747-5520
Lab Phone: 314 747-5521
Other Phone: 314 747-5522
Campus Box: 8103
Fax: 314-362-7051;
kopan@wustl.edu
http://molecool.wustl.edu/kopan.htm
