Diane Barber, PhD

Professor

Cell and Tissue Biology

[email protected]

+1 415 717-7117

The Barber Lab addresses questions on the fundamental cell biology of epithelial plasticity to understand dysregulated functions in human diseases. Our primary focus on how pHi dynamics regulates cancer cell behaviors such as migration and metabolic reprogramming and stem cell behaviors and lineage specification bridges protein electrostatics with cell biology, revealing protonation as a post-translational modification regulating protein conformations and functions. Our secondary focus on the regulation of actin filament dynamics and architectures includes revealing regulatory mechanisms and roles in transformation, stem cell differentiation, and epithelial to mesenchymal transition.

Publications

A role for pH dynamics regulating transcription factor DNA binding selectivity

Nucleic acids research

Kisor KP, Garrido Ruiz, D, Jacobson MP, Barber DL.

A role for pH dynamics regulating transcription factor DNA-binding selectivity.

Nucleic acids research

Kisor KP, Ruiz DG, Jacobson MP, Barber DL

Patient-derived Induced Pluripotent Stem Cells as a Model to Study Frontotemporal Dementia Pathologies.

bioRxiv : the preprint server for biology

Infante-Tadeo S, Barber DL

Arp2/3 complex activity enables nuclear YAP for naïve pluripotency of human embryonic stem cells.

eLife

Meyer NP, Singh T, Kutys ML, Nystul TG, Barber DL

A role for pH dynamics regulating transcription factor DNA binding selectivity.

bioRxiv : the preprint server for biology

Kisor KP, Ruiz DG, Jacobson MP, Barber DL

TCR signaling promotes formation of an STS1-Cbl-b complex with pH-sensitive phosphatase activity that suppresses T cell function in acidic environments.

Immunity

Tsai YL, Arias-Badia M, Kadlecek TA, Lwin YM, Srinath A, Shah NH, Wang ZE, Barber D, Kuriyan J, Fong L, Weiss A

Intracellular pH dynamics regulates intestinal stem cell lineage specification.

Nature communications

Liu Y, Reyes E, Castillo-Azofeifa D, Klein OD, Nystul T, Barber DL

pH dynamics regulates transcription factor-DNA binding.

Biophysical Journal

Kyle Kisor, Diane Barber

Arp2/3 complex activity is necessary for mouse ESC differentiation, times formative pluripotency, and enables lineage specification.

Stem cell reports

Aloisio FM, Barber DL

Low pH Facilitates Heterodimerization of Mutant Isocitrate Dehydrogenase IDH1-R132H and Promotes Production of 2-Hydroxyglutarate.

Biochemistry

Sesanto R, Kuehn JF, Barber DL, White KA

Ethyl Isopropyl Amiloride Decreases Oxidative Phosphorylation and Increases Mitochondrial Fusion in Clonal Untransformed and Cancer Cells.

American journal of physiology. Cell physiology

Manoli SS, Kisor K, Webb BA, Barber DL

pHLARE: A New Biosensor Reveals Decreased Lysosome pH in Cancer Cells.

Molecular biology of the cell

Webb BA, Aloisio FM, Charafeddine RA, Cook J, Wittmann T, Barber DL

An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity.

The Biochemical journal

Luna LA, Lesecq Z, White KA, Hoang A, Scott DA, Zagnitko O, Bobkov AA, Barber DL, Schiffer JM, Isom DG, Sohl CD

Intracellular pH Regulates Cancer and Stem Cell Behaviors: A Protein Dynamics Perspective.

Frontiers in oncology

Liu Y, White KA, Barber DL

Editorial overview: Cell dynamics: Integrating cell dynamics across scales.

Current opinion in cell biology

Barber DL, Trepat X

Filament assembly by the liver phosphofructokinase-1, the “gatekeeper” of glycolysis.

The FASEB Journal

Bradley Webb, Anne Dosey, Torsten Wittmann, Justin Kollmann, Diane Barber

Intracellular pH dynamics and charge-changing somatic mutations in cancer.

Cancer metastasis reviews

White KA, Kisor K, Barber DL

Drosophila anion exchanger 2 is required for proper ovary development and oogenesis.

Developmental biology

Benitez M, Tatapudy S, Liu Y, Barber DL, Nystul TG

Tau repeat regions contain conserved histidine residues that modulate microtubule-binding in response to changes in pH.

The Journal of biological chemistry

Charafeddine RA, Cortopassi WA, Lak P, Tan R, McKenney RJ, Jacobson MP, Barber DL, Wittmann T

ß-Catenin is a pH sensor with decreased stability at higher intracellular pH.

The Journal of cell biology

White KA, Grillo-Hill BK, Esquivel M, Peralta J, Bui VN, Chire I, Barber DL

Formin-dependent TGF-ß signaling for epithelial to mesenchymal transition.

Molecular biology of the cell

Rana MK, Aloisio FM, Choi C, Barber DL

The Glycolytic Enzyme Phosphofructokinase-1 Assembles into Filaments.

Biophysical Journal

Bradley Webb, Annie Dosey, Torsten Wittmann, Justin Kollman, Diane Barber

Cell fate decisions: emerging roles for metabolic signals and cell morphology.

EMBO reports

Tatapudy S, Aloisio F, Barber D, Nystul T

A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.

eLife

Vercoulen Y, Kondo Y, Iwig JS, Janssen AB, White KA, Amini M, Barber DL, Kuriyan J, Roose JP

Cancer-associated arginine-to-histidine mutations confer a gain in pH sensing to mutant proteins.

Science signaling

White KA, Ruiz DG, Szpiech ZA, Strauli NB, Hernandez RD, Jacobson MP, Barber DL

Prominent features of the amino acid mutation landscape in cancer.

PloS one

Szpiech ZA, Strauli NB, White KA, Ruiz DG, Jacobson MP, Barber DL, Hernandez RD

The glycolytic enzyme phosphofructokinase-1 assembles into filaments.

The Journal of cell biology

Webb BA, Dosey AM, Wittmann T, Kollman JM, Barber DL

Cancer cell behaviors mediated by dysregulated pH dynamics at a glance.

Journal of cell science

White KA, Grillo-Hill BK, Barber DL

Increased intracellular pH is necessary for adult epithelial and embryonic stem cell differentiation.

The Journal of cell biology

Ulmschneider B, Grillo-Hill BK, Benitez M, Azimova DR, Barber DL, Nystul TG

A Histidine Cluster in the Cytoplasmic Domain of the Na-H Exchanger NHE1 Confers pH-sensitive Phospholipid Binding and Regulates Transporter Activity.

The Journal of biological chemistry

Webb BA, White KA, Grillo-Hill BK, Schönichen A, Choi C, Barber DL

Structures of Human Phosphofructokinase-1 and Atomic Basis of Cancer-Associated Mutations.

Biophysical Journal

Bradley Webb, Farhad Forouhar, Fu-En Szu, Jayaraman Seetharaman, Liang Tong, Diane Barber

Abstract B65: Dissecting the tumor myeloid compartment reveals rare activating antigen presenting cells, critical for T cell immunity.

Tumor Microenvironment

Miranda Broz, Mikhail Binnewies, Bijan Boldajipour, Amanda Nelson, Joshua Pollock, David Erle, Andrea Barczak, Michael Rosenblum, Adil Daud, Diane Barber, Sebastian Amigorena, Laura J. van 't Veer, Anne Sperling, Denise Wolf, Matthew F. Krummel

Structures of human phosphofructokinase-1 and atomic basis of cancer-associated mutations.

Nature

Webb BA, Forouhar F, Szu FE, Seetharaman J, Tong L, Barber DL

Increased H? efflux is sufficient to induce dysplasia and necessary for viability with oncogene expression.

eLife

Grillo-Hill BK, Choi C, Jimenez-Vidal M, Barber DL

Hypoxia increases the abundance but not the assembly of extracellular fibronectin during epithelial cell transdifferentiation.

Journal of cell science

Rana MK, Srivastava J, Yang M, Chen CS, Barber DL

The Nck-interacting kinase NIK increases Arp2/3 complex activity by phosphorylating the Arp2 subunit.

The Journal of cell biology

LeClaire LL, Rana M, Baumgartner M, Barber DL

Dissecting the Tumor Myeloid Compartment Reveals Rare Activating Antigen-Presenting Cells Critical for T Cell Immunity.

Cancer cell

Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, Amigorena S, Van't Veer LJ, Sperling AI, Wolf DM, Krummel MF

Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.

Cancer cell

Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, Amigorena S, Van't Veer LJ, Sperling AI, Wolf DM, Krummel MF

Filament Assembly by Phosphofructokinase-1, the Gatekeeper of Glycolysis.

Biophysical Journal

Bradley Webb, Larry Ackerman, Diane Barber

Ratiometric imaging of pH probes.

Methods in cell biology

Grillo-Hill BK, Webb BA, Barber DL

pH Sensing by FAK-His58 Regulates Focal Adhesion Remodeling.

The Journal of General Physiology

Chang-Hoon Choi, B Webb, M Chimenti, M Jacobson, Diane L Barber

pH sensing by FAK-His58 regulates focal adhesion remodeling.

The Journal of cell biology

Choi CH, Webb BA, Chimenti MS, Jacobson MP, Barber DL

Electrostatics control actin filament nucleation and elongation kinetics.

The Journal of biological chemistry

Crevenna AH, Naredi-Rainer N, Schönichen A, Dzubiella J, Barber DL, Lamb DC, Wedlich-Söldner R

Considering protonation as a posttranslational modification regulating protein structure and function.

Annual review of biophysics

Schönichen A, Webb BA, Jacobson MP, Barber DL

Phosphorylation of actin-related protein 2 (Arp2) is required for normal development and cAMP chemotaxis in Dictyostelium.

The Journal of biological chemistry

Choi CH, Thomason PA, Zaki M, Insall RH, Barber DL

Characterization of cytoskeletal protein 4.1R interaction with NHE1 (Na(+)/H(+) exchanger isoform 1).

The Biochemical journal

Nunomura W, Denker SP, Barber DL, Takakuwa Y, Gascard P

Phosphorylation of the Arp2 subunit relieves auto-inhibitory interactions for Arp2/3 complex activation.

PLoS computational biology

Narayanan A, LeClaire LL, Barber DL, Jacobson MP

Dynamic actin remodeling during epithelial-mesenchymal transition depends on increased moesin expression.

Molecular biology of the cell

Haynes J, Srivastava J, Madson N, Wittmann T, Barber DL

Dysregulated pH: a perfect storm for cancer progression.

Nature reviews. Cancer

Webb BA, Chimenti M, Jacobson MP, Barber DL

A human MAP kinase interactome.

Nature methods

Bandyopadhyay S, Chiang CY, Srivastava J, Gersten M, White S, Bell R, Kurschner C, Martin C, Smoot M, Sahasrabudhe S, Barber DL, Chanda SK, Ideker T

Nuclear-localized calcineurin homologous protein CHP1 interacts with upstream binding factor and inhibits ribosomal RNA synthesis.

The Journal of biological chemistry

Jiménez-Vidal M, Srivastava J, Putney LK, Barber DL

Expression of actin-interacting protein 1 suppresses impaired chemotaxis of Dictyostelium cells lacking the Na+-H+ exchanger NHE1.

Molecular biology of the cell

Choi CH, Patel H, Barber DL

Molecular Dynamics Simulations Predict A pH-Dependent Conformational Change in the C-Helix of Cell Cycle Checkpoint Kinase Wee1.

Biophysical Journal

Michael S. Chimenti, Mark J.S. Kelly, Diane L. Barber, Matthew P. Jacobson

The sodium-hydrogen exchanger NHE1 is an Akt substrate necessary for actin filament reorganization by growth factors.

The Journal of biological chemistry

Meima ME, Webb BA, Witkowska HE, Barber DL

Mislocalized scaffolding by the Na-H exchanger NHE1 dominantly inhibits fibronectin production and TGF-beta activation.

Molecular biology of the cell

Karydis A, Jimenez-Vidal M, Denker SP, Barber DL

Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding.

The Journal of cell biology

Frantz C, Barreiro G, Dominguez L, Chen X, Eddy R, Condeelis J, Kelly MJ, Jacobson MP, Barber DL

Structural model and functional significance of pH-dependent talin-actin binding for focal adhesion remodeling.

Proceedings of the National Academy of Sciences of the United States of America

Srivastava J, Barreiro G, Groscurth S, Gingras AR, Goult BT, Critchley DR, Kelly MJ, Jacobson MP, Barber DL

Phosphorylation of the Arp2/3 complex is necessary to nucleate actin filaments.

The Journal of cell biology

LeClaire LL, Baumgartner M, Iwasa JH, Mullins RD, Barber DL

Actin co-sedimentation assay; for the analysis of protein binding to F-actin.

Journal of visualized experiments : JoVE

Srivastava J, Barber D

Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells.

The Journal of cell biology

Frantz C, Karydis A, Nalbant P, Hahn KM, Barber DL

Beyond ion translocation: structural functions of the sodium-hydrogen exchanger isoform-1.

Current opinion in nephrology and hypertension

Meima ME, Mackley JR, Barber DL

Intracellular pH sensors: design principles and functional significance.

Physiology (Bethesda, Md.)

Srivastava J, Barber DL, Jacobson MP

The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors.

Proceedings of the National Academy of Sciences of the United States of America

Baumgartner M, Sillman AL, Blackwood EM, Srivastava J, Madson N, Schilling JW, Wright JH, Barber DL

A developmentally regulated Na-H exchanger in Dictyostelium discoideum is necessary for cell polarity during chemotaxis.

The Journal of cell biology

Patel H, Barber DL

Na(+)/H(+) exchanger NHE1 as plasma membrane scaffold in the assembly of signaling complexes.

American journal of physiology. Cell physiology

Baumgartner M, Patel H, Barber DL

Expression profile of genes regulated by activity of the Na-H exchanger NHE1.

BMC genomics

Putney LK, Barber DL

Na-H exchange-dependent increase in intracellular pH times G2/M entry and transition.

The Journal of biological chemistry

Putney LK, Barber DL

Conserved motifs in somatostatin, D2-dopamine, and alpha 2B-adrenergic receptors for inhibiting the Na-H exchanger, NHE1.

The Journal of biological chemistry

Lin CY, Varma MG, Joubel A, Madabushi S, Lichtarge O, Barber DL

Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1.

The Journal of cell biology

Denker SP, Barber DL

Somatostatin, acting at receptor subtype 1, inhibits Rho activity, the assembly of actin stress fibers, and cell migration.

The Journal of biological chemistry

Buchan AM, Lin CY, Choi J, Barber DL

Ion transport proteins anchor and regulate the cytoskeleton.

Current opinion in cell biology

Denker SP, Barber DL

The changing face of the Na+/H+ exchanger, NHE1: structure, regulation, and cellular actions.

Annual review of pharmacology and toxicology

Putney LK, Denker SP, Barber DL

TEL-JAK2 mediates constitutive activation of the phosphatidylinositol 3'-kinase/protein kinase B signaling pathway.

The Journal of biological chemistry

Nguyen MH, Ho JM, Beattie BK, Barber DL

The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor.

The Journal of biological chemistry

Yan W, Nehrke K, Choi J, Barber DL

A common epitope is shared by activated signal transducer and activator of transcription-5 (STAT5) and the phosphorylated erythropoietin receptor: implications for the docking model of STAT activation.

Blood

Barber DL, Beattie BK, Mason JM, Nguyen MH, Yoakim M, Neel BG, D'Andrea AD, Frank DA

A minimal cytoplasmic subdomain of the erythropoietin receptor mediates p70 S6 kinase phosphorylation.

Experimental hematology

Zhang MY, Barber DL, Alessi DR, Bell LL, Stine C, Nguyen MH, Beattie BK, Cheung JY, Miller BA

Direct binding of the Na--H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H(+) translocation.

Molecular cell

Denker SP, Huang DC, Orlowski J, Furthmayr H, Barber DL

The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent manner to the erythropoietin receptor.

The Journal of biological chemistry

Mason JM, Beattie BK, Liu Q, Dumont DJ, Barber DL

Effect of Rho GTPases on Na-H exchanger in mammalian cells.

Methods in enzymology

Denker SP, Yan W, Barber DL

Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission.

Cell

Chaudhry FA, Reimer RJ, Krizaj D, Barber D, Storm-Mathisen J, Copenhagen DR, Edwards RH

Inhibition of calcineurin phosphatase activity by a calcineurin B homologous protein.

The Journal of biological chemistry

Lin X, Sikkink RA, Rusnak F, Barber DL

Fusion of the ets transcription factor TEL to Jak2 results in constitutive Jak-Stat signaling.

Blood

Ho JM, Beattie BK, Squire JA, Frank DA, Barber DL

p160ROCK mediates RhoA activation of Na-H exchange.

The EMBO journal

Tominaga T, Ishizaki T, Narumiya S, Barber DL

Na-H exchange acts downstream of RhoA to regulate integrin-induced cell adhesion and spreading.

Molecular biology of the cell

Tominaga T, Barber DL

Maintenance of human T cell anergy: blocking of IL-2 gene transcription by activated Rap1.

Science (New York, N.Y.)

Boussiotis VA, Freeman GJ, Berezovskaya A, Barber DL, Nadler LM

Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins.

Blood

Barber DL, Mason JM, Fukazawa T, Reedquist KA, Druker BJ, Band H, D'Andrea AD

Erythropoietin activates Raf1 by an Shc-independent pathway in CTLL-EPO-R cells.

Blood

Barber DL, Corless CN, Xia K, Roberts TM, D'Andrea AD

Activation of Na+-H+ exchange is necessary for RhoA-induced stress fiber formation.

Journal of Biological Chemistry

Zinaida S. Vexler, Marc Symons, Diane L. Barber

A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange.

Proceedings of the National Academy of Sciences of the United States of America

Lin X, Barber DL

The cytokine-activated tyrosine kinase JAK2 activates Raf-1 in a p21ras-dependent manner.

Proceedings of the National Academy of Sciences of the United States of America

Xia K, Mukhopadhyay NK, Inhorn RC, Barber DL, Rose PE, Lee RS, Narsimhan RP, D'Andrea AD, Griffin JD, Roberts TM

Activation of Na+-H+ exchange is necessary for RhoA-induced stress fiber formation.

The Journal of biological chemistry

Vexler ZS, Symons M, Barber DL

Galpha12 differentially regulates Na+-H+ exchanger isoforms.

The Journal of biological chemistry

Lin X, Voyno-Yasenetskaya TA, Hooley R, Lin CY, Orlowski J, Barber DL

A constitutively activated chimeric cytokine receptor confers factor-independent growth in hematopoietic cell lines.

Blood

Shikama Y, Barber DL, D'Andrea AD, Sieff CA

G alpha 13 stimulates Na+-H+ exchange through distinct Cdc42-dependent and RhoA-dependent pathways.

The Journal of biological chemistry

Hooley R, Yu CY, Symons M, Barber DL

[12] Regulation of Na+-H+ exchange by G protein-coupled receptors.

Receptor Molecular Biology

Kim A. Neve, Mary P. Rosser, Diane L. Barber

The Fanconi anemia polypeptide FACC is localized to the cytoplasm.

Proceedings of the National Academy of Sciences of the United States of America

Yamashita T, Barber DL, Zhu Y, Wu N, D'Andrea AD

Subtype-specific signaling mechanisms of somatostatin receptors SSTR1 and SSTR2.

The Journal of biological chemistry

Hou C, Gilbert RL, Barber DL

A dominant negative erythropoietin (EPO) receptor inhibits EPO-dependent growth and blocks F-gp55-dependent transformation.

Molecular and cellular biology

Barber DL, DeMartino JC, Showers MO, D'Andrea AD

G alpha 13 stimulates Na-H exchange.

The Journal of biological chemistry

Voyno-Yasenetskaya T, Conklin BR, Gilbert RL, Hooley R, Bourne HR, Barber DL

Guanine nucleotides regulate beta-adrenergic activation of Na-H exchange independently of receptor coupling to Gs.

The Journal of biological chemistry

Barber DL, Ganz MB

The erythropoietin receptor and the molecular basis of signal transduction.

Seminars in hematology

Barber DL, D'Andrea AD

Mutant constructs of the beta-adrenergic receptor that are uncoupled from adenylyl cyclase retain functional activation of Na-H exchange.

Molecular pharmacology

Barber DL, Ganz MB, Bongiorno PB, Strader CD

Fatty acids stereospecifically stimulate neurotensin release and increase [Ca2+]i in enteric endocrine cells.

The American journal of physiology

Barber DL, Cacace AM, Raucci DT, Ganz MB

Mechanisms of receptor-mediated regulation of Na-H exchange.

Cellular signalling

Barber DL

Multiple receptors coupled to adenylate cyclase regulate Na-H exchange independent of cAMP.

The Journal of biological chemistry

Ganz MB, Pachter JA, Barber DL

Beta-adrenergic and somatostatin receptors regulate Na-H exchange independent of cAMP.

The Journal of biological chemistry

Barber DL, McGuire ME, Ganz MB

Canine enteric submucosal cultures: transmitter release from neurotensin-immunoreactive neurons.

Neuroscience

Barber DL, Buchan AM, Leeman SE, Soll AH

Somatostatin and muscarinic inhibition of canine enteric endocrine cells: cellular mechanisms.

The American journal of physiology

Barber DL, Gregor M, Soll AH

Morphologic and physiologic studies of canine ileal enteroglucagon-containing cells in short-term culture.

Gastroenterology

Buchan AM, Barber DL, Gregor M, Soll AH

Cloning and sequence analysis of cDNA for the canine neurotensin/neuromedin N precursor.

Proceedings of the National Academy of Sciences of the United States of America

Dobner PR, Barber DL, Villa-Komaroff L, McKiernan C

Neurotensin-containing neurons in the canine enteric innervation.

Neuroscience letters

Buchan AM, Barber DL

Chapter 9 Separation of Epithelial Cells from Gastric and Intestinal Mucosa.

Cell Separation

DIANE L. BARBER, ANDREW H. SOLL

Isolated canine ileal mucosal cells in short-term culture: a model for study of neurotensin release.

The American journal of physiology

Barber DL, Buchan AM, Walsh JH, Soll AH

Regulation of neurotensin release from canine enteric primary cell cultures.

The American journal of physiology

Barber DL, Buchan AM, Walsh JH, Soll AH