Life Within a Box

Through dance, this piece explores limitations or, more specifically, the situation individuals face when they are put “in a box.” This boxing in can be of one\u27s own doing, in the mind, or the doing of others, through words, actions, or societal expectations. I believe that in life there are many times when individuals think or are told what they can and cannot or should and should not do, which limits them from reaching their full potential. As unique individuals, we cannot be placed into neatly defined boxes. Through my choreography, I explore the act of being put in a box, the feelings one has when confined or limited, and the act of trying to escape one’s box. Movement is contrasted between bound and small and unrestricted and full to show the contrast between being confined in a box and free to explore

Polycomb Paralog Chromodomain Inhibitors Active Against Both CBX6 and CBX8

Methyllysine reader proteins bind to methylated lysine residues and alter gene transcription by changing the compaction state of chromatin or by the recruitment of other multiprotein complexes. The polycomb paralog family of methyllysine readers bind to trimethylated lysine on the tail of histone 3 via a highly conserved aromatic cage located in their chromodomains. Each of the polycomb paralogs are implicated in several disease states. CBX6 and CBX8 are members of the polycomb paralog family with two structurally similar chromodomains. By exploring the structure-activity relationships of a previously reported CBX6 inhibitor we have discovered more potent and cell permeable analogs. Our current report includes potent, dual-selective inhibitors of CBX6 and CBX8. We have shown that the –2 position in our scaffold is an important residue for selectivity amongst the polycomb paralogs. Preliminary cell-based studies show that the new inhibitors impact cell proliferation in a rhabdoid tumor cell line. This report includes data on inhibitor design, inhibitor synthesis, compound characterization by LCMS, compound activity by fluorescence polarization, analysis of structure-activity relationships, rhabdoid tumor cell line activity