Diane Barber

Diane L. Barber, from Marin, California, is an American cell physiologist and cell biologist. She is professor and chair of the Department of Cell and Tissue Biology at University of California, San Francisco School of Dentistry. In 2012 she became elected Fellow of the American Association for the Advancement of Science as recognition for her "distinguished contributions on cell signaling by plasma membrane ion transport proteins and on the design and function of proteins regulated by intracellular pH dynamics."

Barber is a second-generation American Armenian. Her grandparents emigrated from Diyarbakir and Harput of the Anatolia region of Eastern Turkey in the early 1990s.Sheeearned a B.Sc. in biological sciences in 1975 and an M.Sc. in physiology in 1977 from University of California, Davis, followed by a Ph.D. in anatomy underAndrew Soll in 1985 from University of California, Los Angeles .She was an NIH postdoctoral fellow (NRSA) in the Department of Physiology at the University of Massachusetts Medical Center in Worcester. She joined the faculty of the Department of Surgery, Section of Anatomy at Yale University in 1987. In 1991, she returned to California and became assistant professor in the Department of Stomatology and Surgery at the University of California, San Francisco. She is currently a professor and vice chair of the Department of Cell and Tissue Biology at University of California, San Francisco.

Barber started her career in biological research as a Ph.D. student, at the Centre for Ulcer Research and Education associated with the University of California at Los Angeles, during her Ph.D. studies inAnatomy in 1985.She went on to complete a postdoctoral fellowship with Susan Leeman at the University of Massachusetts, before taking up her first academic appointment at Yale University in 1987. She became a faculty member at Yale University in the Department of Surgery/Section of Anatomy. AtYale she became interested in the role of intracellular pH (pHi)and regulation of cellular function, which has remained her research interest.

Barber's research addresses questions on how signaling networks and the actin cytoskeletoncontrol normal and pathological cell behavior, particularly the post-translational modifications of proteins by protonation and by phosphorylation. Her laboratory is specifically focused on bridging both structural biology and cell biology in three main categories: cancer cell biology, stem cell differentiation, and neurodegeneration.

One focus of her research is on cancer cell biology, specifically in regards to the pHi (intracellular pH) of cancer cells., which is increased in comparison to normal cells. The research focuses on the relationship between the increased pHiand their ability to perform necessary functions. The laboratory group showed in molecular detail how it is necessary for the directed cell migration for metastasis. This was accomplished through the use of selective pH sensors that defined how proteins were regulated by cellular changes in pH. The group subsequently worked on the effect of increased pHi on the glycolytic enzymes necessary for metabolic programming, somatic mutation biology, and tumorigenic behaviorss. The research uses optogenetic tools to control the pHi of the cells, biosensors that are genetically encoded to quantify the pHi of single cancer cells as well as cells in vivo, and computational programming to identify ionizable residues in proteins and amino acid mutation signatures that are present in numerous cancer databases.

The second focus of Bherarber's laboratory is in stem cell differentiation, in collaboration with the laboratory of Todd Nystul. The group studies how intracellular pH and actin filament dynamics regulate stem cell differentiation. Through their work, the group has been able to show that daughter cells have a higher pHi than naive adult and embryonic stem cells that is necessary for their differentiation. Therefore, the laboratory is seeking to find a method to identify the pH sensors that are necessary for the differentiation of stem cells. Additionally, the laboratory studies how actin filament remodeling is necessary for the differentiation of naive embryonic stem cells. The current focus is on the transcriptional events linked to these actin dynamics.

The final main focus of her research is on neurodegeneration, as part of a 4-lab collaboration with thegroups of Aimee Kao, Matt Jacobson, and Torsten Wittman. The main focus of this area is to identify the dysregulated cellular pH dynamics that results in the pathology associated Alzheimer's disease. The laboratory is focused on reversing the decreased intracellular pH and increased lysosomal pH that is commonly associated with neurodegeneration. This team recently received one of five Allen Distinguished Investigator (ADI) grants of $1.32 million.

1. Srivastava, J, Barber, DL, and Jacobson, MP. 2007 Intracellular pH sensors: design principles and functional significance. Physiology 22:30-39.
2. Schönichen, A, Webb, BE, Jacobson, MP, and Barber, DL. 2013 Considering protonation as a posttranslational modification regulating protein structure and function. Ann Rev Biophys. 42:289-314. PMID 23451893
3. Webb, BE, Chimenti, M, Jacobson, MP and Barber, DL. 2011 Dysregulated pH: a perfect storm for cancer progression. Nat Rev Cancer. 11:671-677. PMID 21833026
4. Grillo-Hill, BK, Choi, CC, Jimenez-Vidal, M and Barber, DL. 2015 Increased H+ efflux is sufficient to induce dysplasia and necessary for viability with oncogene expression. eLife 4:e03270. PMID 25793441
5. 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 [Using acid to find direction. J Cell Biol 2002 159:911] and cited in Faculty of 1000; Factor 13)
6. Frantz, C, Barreiro, G, Dominguez, L, Chen, X, Eddy, R, Condeelis, J, Kelly, M, Jacobson, MP and Barber, DL. 2008 Cofilin is a pH sensor for actin free barbed end formation. J. Cell Biol. 183:865-879 (Highlighted in Journal; Cited in Faculty of 1000, Factor 8.0) PMID 19029335
7. Srivastava, J, Barreiro, G, Groscurth, S, Gringas, AR, Goult, BT Critchley, DR, Kelly, MJS, 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. 105:14436-14441. PMID 18780792
8. Choi, CC, Webb, BA, Chimenti, MS, Jacobson, MP and Barber, DL. 2013 pH sensing by FAK-His58 regulates focal adhesion remodeling. J Cell Biol. 202:849-59. [Commentary: C. Lawson and D. D. Schlaepfer, "pHocal adhesion kinase regulation is on a FERM foundation", J. Cell. Biol., 202:833-836.] [Commentary: K. Legg, "Factoring pH into FAK phosphorylation", Cell Migration Gateway.]; cited in Faculty of 1000 Prime) PMID 24043700
9. LeClaire, LL III, 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 and cited in Faculty of 1000; Factor 8.0) PMID 22125478
10. Narayanan, A, LeClaire, LL, Barber, DL, and Jacobson, MP. 2011 Phosphorylation of the Arp2 subunit relieves auto-inhibitory interactions for Arp2/3 complex activation. PLoS Comput Biol. 7:e1002226. PMID 22125478
11. Choi, CC,* Thomason, PA,* Zaki, M, Insall, RH, and Barber, DL. 2013 Phosphorylation of actin-related protein 2 (Arp2) is required for normal development and cAMP chemotaxis in Dictyostelium. J Biol Chem. 288(4):2464-74. (*authors contributed equally) PMID 23223240
12. LeClaire, LL, Rana, MK, Baumgartner, M and Barber, DL. 2015 Arp2 phosphorylation: Functional significance and regulation by the Nck-interacting kinase NIK. J. Cell. Biol. 208:161-170. PMID 25601402 (Highlighted commentary in Journal 208:138)
13. Denker, SP. Huang, DC, Orlowski, J, Furthmayr, H and Barber, DL. 2000 Direct binding the Na-H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H+ translocation. Mol Cell. 6:1425-1436.
14. Tominaga, T, Ishizaki, T, Narumiya, D, and Barber, DL. 1998 p160ROCK mediates RhoA activation of Na- H exchange. EMBO J. 17:4712-4722.
15. Meima, ME, Webb, BE, Witkowska, HE, and Barber, DL. 2009 The Na-H exchanger NHE1 is an Akt substrate necessary for actin filament reorganization by growth factors. J Biol Chem. 284(39):26666-75. PMID 19622752
16. Lin, X and Barber, DL. 1996 A calcineruin homologous protein inhibits GTPase activation of Na-H exchange. Proc. Natl. Acad. Sci. 93:12631-12636.

Barber is the Leland and Gladys Barber Endowed Chair in Density at the University of California, San Francisco.A

From 1995 to 2000, Barber was named an Established Investigator by the American Heart Association. From 1998 and continuing into the present day, Barber has been on the editorial board of the American Journal of Physiology: Cell Physiology. From 1998 to 1999, Barber served on the National Review Committee for Transport and Metabolism of the American Heart Association. In 1998, Barber was awarded the Innovation in Basic Sciences Award at the University of California, San Francisco. From 2000 to 2002, Barber was the co-chair of the National Review Committee for Transport and Metabolism for the American Heart Association. In 2001, Barber became the vice-chair of the Gordon Conference on Molecular Pharmacology, and in 2003, she became the chair. Barber was a member of the NIH CDF3 Study Section from 2001 to 2003.In 2005, Barber received the Sandler Program Integrative Award.

In 2012, Barber wasselected as a fellow of the American Association for the Advancement of Science (AAAS).

In 2016, Barber was appointed as the chair of Women in Cell Biology (WICB) for the American Society for Cell Biology (ASCB). Her term began on January 1, 2016. She succeeded the last chair, Sandra K. Masur.