MY FOCUS Many interesting potential targets are protein-protein interactions. However, these are not considered traditionally 'druggable' and often do not yield useful 'hits' in high-throughput screens. Past projects have therefore explored minimal requirements for protein-protein and protein-peptide recognition to better understand which targets may be tractable. For example, we discovered a general recognition motif that directs protein inhibitors of canonical Wnt signaling (SOST, DKK1) to the extracellular co-receptors LRP5 and LRP6, and we characterized the inhibitor/co-receptor complexes using mutagenesis and biophysical methods. Peptide inhibitors evolved through phage display were used to assess the potential for small-molecule intervention in this important pathway. A second major project is to understand substrate recognition and catalysis by the Polycomb E3 ubiquitin ligase BMI1/Ring1b and other related PRC1 ligases. Also in the area of ubiquitin signaling, we uncovered a phospho-regulatory mechanism for the deubiquitinase OTUD5/DUBA. Recently, we have been studying the recognition of epigenetic modifications by bromodomain “reader” modules using synthetic peptide arrays, small-molecule probes, and cellular studies. Our interest in epigenetic regulation has expanded to include chromatin remodeling complexes. A recent postdoctoral project centered on the ISWI family of chromatin remodelers: this involved proteomics, biochemistry, and cell line engineering to better understand the function of ISWI regulatory subunits.