David L. Brautigan, PhD

David L. Brautigan, PhD

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Protein Phosphatases and Phosphorylation in Cell Signaling

The Brautigan research goal is to discover how protein phosphorylation and the enzymes called protein Ser/Thr phosphatases (called the PPP family) control intracellular signaling pathways and processes including mitosis, movement and metabolism.  This research is relevant to understanding normal physiology as well as the pathology encountered in human cancer. Genomics has shown that the PPP enzymes are extraordinarily conserved in all eukaryotes (e.g. mammals, Xenopus, Drosophila, C. elegans, S. pombe S. cerevisiae). Humans and yeast have about the same total number of PPP genes, in separate functional classes (i.e. PP1, PP2A, PP4, PP6). These classes of PPP are all sensitive to inhibition by nanomolar concentrations of natural toxins produced by marine dinoflagellates, or blue-green algae, or insects. Individual human PPP proteins can substitute in place of their yeast homologues, but not PPP of other functional classes, showing: 1) separate PPP are functionally equivalent across evolution, but 2) each class has a distinctive biological role. This allows them to use the results from genetic experiments in various model organisms to guide their study the human versions of PPPs.  The PPP are essential for cell survival and critical to mitosis. This research involves collaborations with Cancer Center investigators P. Todd Stukenberg, on mitotic cell regulation of PPP and the process of chromosome segregation, and with James Larner to study ionizing radiation and cell cycle checkpoints. Translational projects involve using reagents developed for discovery to monitor the signaling events in tumors and response of tumors to chemotherapy.