Director, Program in Biomedical Sciences
Born in Pittsburgh, PA; B.S. from Penn State University, 1992; Ph.D. from UC San Diego, graduate mentor Mike Levine (now at UC Berkeley); postdoc in Notch signaling with Jim Posakony; started lab at U-M in 2003.
A few highly conserved cell signaling pathways, such as Notch, Wnt, Hedgehog, TGF-β/BMP, and RTK/Ras/MAPK, are essential for specifying a vast number of cell fates during embryonic development and adult stem cell function. These same pathways are central to many human diseases, most notably cancer, which is often caused by aberrant signaling.
Signaling pathways affect cell fate primarily by altering the activity of transcription factors (TFs), which in turn control the expression of pathway target genes. Signal-regulated enhancers located near pathway target genes contain binding sites for signal-regulated TFs and for other, tissue- or cell-type-specific TFs; interactions among these factors determine the expression pattern of the target gene.
Very basic questions about biological patterning information and cis-regulatory logic remain unanswered. The gaps in our knowledge are best illustrated by the fact that “synthetic” versions of well-characterized enhancers (i.e., combinations of the known transcription factor binding sites) nearly always fail to drive gene expression in vivo. Therefore, it seems that we don’t yet know all of the component parts of the enhancer, or its basic structure. We are employing transgenic, genetic, biochemical, evolutionary, and bioinformatics approaches to the study of these problems.