Mentor Name: Kyle MacQuarrie

Work by Dr. MacQuarrie and collaborators has previously shown that there is a predictable relationship during normal development between the nucleolus and centromeres, with both the number of detectable nucleoli and the overlap between centromeres and nucleoli changing with development in numerous cell types. A similar pattern is seen with cancer cells, including rhabdomyosarcoma cells, with baseline tumor cells having a pattern of interaction similar to what is seen in less developed normal cells, and that pattern changing in response to forced differentiation in rhabdomyosarcoma cells to resemble the pattern seen after normal skeletal muscle cell differentiation. Given the known relationship between developmental state and chemotherapy sensitivity in rhabdomyosarcoma, we will test the hypothesis that the nucleolus and centromeres will exhibit a different pattern of interaction in chemoresistant rhabdomyosarcoma cells compared to non-chemoresistant cells. Centromeres and the nucleoli will be visualized in each cell type using immunofluorescence and their interaction quantified and compared. Pending those results, we may also determine the effect that induced differentiation has in the chemoresistant cells on that interaction, and test the hypothesis that the pattern of change will differ in the resistant cells. This project will therefore help test the hypothesis that nuclear organization is changed in chemotherapy resistant rhabdomyosarcoma cells, and that such changes affect cellular function.