Biomedical Sciences Graduate Program | University of California, San Francisco

Diane Barber, PhD
Signal Transduction and Cytoskeleton Organization

Selected Publications | Complete Publications

phone	(415) 476-3764
email	diane.barber@ucsf.edu
additional websites	Lab Website Cancer Center
secondary research affiliation	none

Our research aims to understand how chemical cues such as growth factors and mechanical cues such as wounding and tensional forces regulate cell migration, actin cytoskeleton remodeling, and cell proliferation. We also are studying the role of these processes in cancer progression and metastasis. Our specific focus is determining how dynamic changes in intracellular pH induced by extracellular cues control cell migration and proliferation, and we study this from molecules to cells. H+ fluxes at the plasma membrane have an evolutionarily conserved role in regulating cytoskeleton dynamics and cell migration, although through poorly understood mechanisms. Moreover, increased intracellular pH is a common characteristic of cancer cells and is predicted to be a common driving force for cancer progression to metastasis. We are determining at the molecular level how protonation of amino acids functions as a post-translational mechanism to regulate protein activities, ligand-binding affinities, and stability. We identified the molecular basis for pH-sensing by several actin binding proteins and are currently applying our analysis of pH sensors to include metabolic enzymes and cell cycle regulators that have been shown biochemically and functionally to be both pH-sensitive and important in cancer progression.

Selected Publications

Denker, S.P. Huang , D.C. , Orlowski, J., Furthmayr, H., and Barber, D.L. 2000 Direct binding the Na-H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H + translocation. Molecular Cell 6:1425-1436.

Denker, SP, Barber, DL. 2002 Ion transport proteins anchor and regulate the cytoskeleton. Current Opinion in Cell Biology 14:214-220.

Denker SP and Barber DL. 2002 Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J. Cell Biol. 159:1087-1096. (Highlighted in Journal and cited in Faculty of 1000; Factor 8.1)

Patel, H. and Barber, DL. 2005 A developmentally-regulated Dictyostelium Na-H exchanger is necessary for cell polarity and chemotaxis J Cell Biol 169:321-329.

Baumgartner, M., Blackwood, E.M., Sillman, A., Srivastava, J., Madson, N., Schilling, J.W., Wright, J.H., and Barber, DL. 2006 The Nck-interacting kinase NIK phosphorylates ERM proteins for formation of lamellipodium by growth factors. Proc. Natl. Acad. Sci. 103:13391-13396.

Svrivastava J, Barber DL and Jacobson MP. 2007 Intracellular pH sensors: design principles and functional significance. Physiology 22:30-39.

Frantz C, Karydis A, Nalbant P, Hahn KM and Barber DL. 2007 Positive feedback between Cdc42 activity and H+ efflux by the Na-H Exchanger NHE1 for polarity of migrating cells. J. Cell Biol. 179:403-410. (Highlighted in Journal)

LeClaire LL 3rd, Baumgartner M, Iwasa JH, Mullins RD and Barber DL. 2008 Phosphorylation of the Arp2/3 complex is necessary to nucleate actin filaments. J. Cell Biol. 182:647-654. (Highlighted in Journal; Cited in Faulty of 1000, Factor 6.0)

Srivastava J, Barreiro G, Groscurth S, Gingras AR, Goult BT, Critchley DR, Kelly MJ, Jacobson MP and Barber DL. 2008 Structural model and functional significance of pH-dependent talin-actin binding for focal adhesion remodeling. Proc. Natl. Acad. Sci. USA 105:14436-14441.

Frantz C, Barreiro G, Dominguez L, Chen X, Eddy R, Condeelis J, Kelly MJ, Jacobson MP and Barber DL. 2008 Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding. J. Cell Biol. 183:865-879. (Highlighted in Journal; Cited in Faulty of 1000, Factor 6.0)

updated August 2009