Stuart L. Schreiber
Department of Chemistry
Harvard University
12 Oxford Street
Cambridge, MA 02138
tel: (617) 495-1426 fax: (617) 495-0751
email: sls@slsiris.harvard.edu
Schreiber Lab
Web Page
Research in the Schreiber laboratory integrates several disciplines,
including synthetic organic chemistry, protein and structural biochemistry,
and molecular and cellular biology. In these studies, cell permeable molecules
have been synthesized and used to understand and control signal transduction
pathways. A general method has been developed to prepare conditional alleles
of signaling proteins, where a gain of function results from the use of
synthetic "dimerizers" that bring two halves of the encoded protein
together, and a loss of function results from synthetic ligands that bind
specifically to the encoded protein. This chemical approach has illuminated
several processes in cell biology and has promise in developmental biology
and medicine. Examples are seen in the group's studies of immunophilin-natural
product complexes that led to the identification of calcineurin as a mediator
of T cell receptor signaling and of FRAP as a mediator of signaling that
links mitogenic pathways to the cell cycle machinery. Their combined use
of combinatorial synthesis and multidimensional NMR led to the structure
determination of SH3 domains complexed to natural and non-natural ligands
and to a general understanding of how these receptors function. The family
of cell permeable ligands that induce intracellular proteins to associate,
developed jointly with Gerald Crabtree, has been used to gain control over
transcriptional activation and signal transduction, including pathways
emanating from the T cell receptor and the apoptosis-inducing Fas antigen,
and other cellular processes such as intracellular protein degradation
and translocation.
Selected Publications:
Spencer, D., Wandless, T.J., Schreiber, S. L., and Crabtree, G.R. (1993).
Controlling Signal Transduction with Synthetic Ligands. Science
262: 1019-1024.
Brown, E.J., Albers, M.W., Shin, T. B., Ichikawa, K., Keith, C.T., Lane,
W.S., Schreiber, S. L. (1994). A Mammalian Protein Targeted by G1-Arresting
Rapamycin-Receptor Complex. Nature 369: 756-758.
Feng, S., Chen, J. K., Yu, H. , Simon, J. A., Schreiber, S. L. (1994).
Two Binding Orientations for Peptides to Src SH3 Domain: Development of
a General Model for SH3-Ligand Interactions. Science 266:
1241-1247.