Perturbing TGF-β signal transduction to direct human embryonic stem cell fates

BIOL 143

Lingyin Li, lingyinli@wisc.edu, Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, Brendan P. Orner, orner@biochem.wisc.edu, Departments of Biochemistry and Chemistry, University of Wisconsin, Madison, WI 53706, Andrew P. Hinck, hinck@uthscsa.edu, Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, and Laura L. Kiessling, kiessling@chem.wisc.edu, Departments of Chemistry and Biochemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706.
Human embryonic stem (ES) cells are blastocyst-derived cells capable of differentiating into any cell type. Human ES cells hold promise for therapeutic applications and for fundamental understanding of early human development. Major practical challenges in human ES cell studies are to maintain their pluripotency and to direct their differentiation toward specific cell lineages. To achieve this goal, we will identify and utilize small molecules that activate or inhibit specific signaling pathways to dissect their roles in human ES cell fate specification. Specifically, we are interested in the role of transforming growth factor beta (TGF-β) signaling. We have identified peptide ligands for TGF-β3 and its receptors (TβR1 and TβR2) by screening phage-displayed random peptide libraries. The affinities and specificities of the peptide ligands for their target proteins have been assessed using battery of assays. Identified peptides can potentially inhibit signaling by blocking the receptor-binding site of TGF-β as well as activate the signaling through clustering the receptors. Therefore, the peptides comprise the means to deliver the desired level of TGF-β signaling to human ES cells.
 

Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Biological Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006