Diane L. Barber Ph.D.
Signal Transduction and Cytoskeleton Organization
Dr. Barber’s research program addresses fundamental questions on how cell behaviors are regulated, with an emphasis on differences between cancer and normal cells. Her work is at the interface of cell signaling and cell biology, with a current focus on cancer cell behaviors. Her group uses a number of different cell and animal model systems to investigate proliferation, glycolytic metabolism and migration of mammalian cells, chemotaxis of Dictyostelium cells, and dysplasia in Drosophila. They are asking how distinct signaling networks regulate these behaviors, with an emphasis on post-translational modification of proteins by protonation and by phosphorylation. An innovative aspect of Dr. Barber’s research is revealing how dynamic changes in intracellular pH (pHi) drive cell processes, such as cytoskeleton remodeling for cell migration, cell cycle progression for cell proliferation, and enzyme localization and activity for glycolytic metabolism. In collaborations with Matthew Jacobson (computational biology) and Mark Kelly (NMR spectroscopy) at UCSF their work highlights how protonation acts as a post-translational modification regulating protein structure and function (Schonichen et al., 2013 Ann. Rev. Biophysics 42:289). They are determining the structural design principles and functional significance of pH sensors, or proteins with activities or ligand-binding affinities that are sensitive to physiological changes in pH. Focusing on pHi-dependent cell behaviors they identified mechanisms of pH sensing by proteins regulating cell polarity (Frantz et al., 2007 J. Cell Biol. 179:403), actin filament assembly (Frantz et al., 2008 J. Cell Biol. 183:865), and focal adhesion remodeling (Srivastava et al., 2008 Proc. Natl. Acad Sci. 105:14436; Choi et al., 2013 J. Cell Biol. 202:849). As they recently described (Webb et al., 2011 Nat. Rev. Cancer 11:671), increased pHi is a hallmark of most cancers, which highlights the clinical significance of understanding how pHi dynamics regulates cell behaviors.