Prof Karl Matter

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Personal Profile

Name: Karl Matter Email: k.matter@ucl.ac.uk
Title: Prof Tel: 020 7608 4014
Department: Inst Ophthalmology - Cell Biology Fax: 020 7608 4034
Position: Professor of Cell Biology Address: UCL Institute of Ophthalmology, Bath Street London, London, EC1V 9EL
Research Domain: Ageing, Basic Life Sciences, Biomedical Imaging (Frontier Disciplines), Cancer, Data Science, Experimental Medicine, Human Wellbeing, Infection, Immunology & Inflammation, Neuroscience, Personalised Medicine, Populations & Lifelong Health Web Page: Personal Web Page

Profile

Research Description

Epithelial cells perform crucial functions in organs and tissues, ranging from the liver and the intestine, to the brain and the retina. To perform their physiological functions, epithelial cells need to polarise – form distinct cell surface domains that are biochemically and functionally distinct – and adhere to each other to form continuous sheets of differentiated cells that function as barriers between body compartments and to the environment. Many diseases originate in or affect particular epithelia, ranging from cancer to chronic, inflammatory and age-related diseases, such as asthma and age-related retinal degenerations. 

We are interested in different aspects of epithelial cell biology and have made significant contributions to the understanding of how epithelial cells polarise and generate distinct cell surface domains, how epithelial cells adhere to each other to form functional barriers, how such mechanisms contribute to the regulation of epithelial cell behaviour and differentiation, and how they are affected by and contribute to disease. 


Since I started my laboratory at UCL in 2001, we have focused on the structure and functions of tight junctions and, particularly, on how tight junctions receive signals that guide junction assembly and function and how they signal to the cell interior to guide cell proliferation and survival. This led to important findings that provided new insights into the structure and function of tight junctions.
Among which was the discovery of ZONAB, the first description of a signalling mechanism by which tight junctions can directly regulate gene expression. We demonstrated that ZONAB is activated during proliferation and stress signalling, and regulates genes transcriptionally and posttranscriptionally that are important for cell proliferation and survival (e.g., cyclin D1, PCNA, p21). We also isolated physically and functionally interacting proteins such as the heat shock protein Apg-2, a protein that regulates junction assembly, and the cell cycle kinase CDK4. 


We have discovered a new cell-cell adhesion protein, MarvelD3. This protein is a component of tight junctions, the cell-cell junction that mediates epithelial barrier formation. We have demonstrated that this adhesion protein is not a critical component of the actual intercellular barrier but is the cell surface receptor of a new signalling mechanism that regulates MAP Kinase signalling and, thereby, gene expression. This pathway regulates epithelial proliferation and migration, and is an important component of the epithelial stress response. 


A main research effort has focused on the molecular mechanisms that regulate epithelial Rho GTPase signalling. Rho GTPases are regulatory switches of central signalling pathways that regulate all aspects of epithelial proliferation, differentiation and survival. However, little had been known about how these common signalling components are regulated and recruited for specific signalling functions. We have discovered multiple regulators that drive specific activation or inactivation of Rho GTPases and, thereby, control epithelial proliferation and gene expression, mitosis and genome integrity, stress response and survival, polarization and morphogenesis.


Research Activities

Cell adhesion and signalling

Differentiation of polarised epithelia

Epithelial Cell Biology

Hugh Davson Professor of Biomedical Research

Signal Transduction in Vascular Endothelial Cells

Education Description

UCL Collaborators

Prof John Greenwood; Dr Virginia Calder; Prof Philip Luthert; Dr Patric Turowski; Dr Marcus Fruttiger; Prof Arne Akbar; Prof Robin Ali; Prof Maria Balda

External Collaborators

Publications

    2015

    • Tornavaca O, Chia M, Matter K, Balda MS, Schwartz MA, Dufton N, Almagro LO, Randi AM, Conway DE (2015). ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. Journal of Cell Biology, 208(6), 821 - 838. doi:10.1083/jcb.201404140

    2014

    • Zihni C, Balda MS, Matter K (2014). Signalling at tight junctions during epithelial differentiation and microbial pathogenesis.. J Cell Sci, 127(Pt 16), 3401 - 3413. doi:10.1242/jcs.145029
    • Anton KA, Sinclair J, Ohoka A, Kajita M, Ishikawa S, Benz PM, Renne T, Balda M, Jorgensen C, Matter K, Fujita Y (2014). PKA-regulated VASP phosphorylation promotes extrusion of transformed cells from the epithelium.. J Cell Sci, 127(Pt 16), 3425 - 3433. doi:10.1242/jcs.149674
    • Matter K, Balda MS (2014). SnapShot: Epithelial tight junctions.. Cell, 157(4), 992 - 992.e1. doi:10.1016/j.cell.2014.04.027
    • Steed E, Elbediwy A, Vacca B, Dupasquier S, Hemkemeyer SA, Suddason T, Costa AC, Beaudry JB, Zihni C, Gallagher E, Pierreux CE, Balda MS, Matter K (2014). MarvelD3 couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival.. J Cell Biol, 204(5), 821 - 838. doi:10.1083/jcb.201304115
    • Zihni C, Munro PM, Elbediwy A, Keep NH, Terry SJ, Harris J, Balda MS, Matter K (2014). Dbl3 drives Cdc42 signaling at the apical margin to regulate junction position and apical differentiation.. J Cell Biol, 204(1), 111 - 127. doi:10.1083/jcb.201304064
    • Balda MS, Matter K (2014). Tight junctions in health and disease.. Semin Cell Dev Biol, 36, 147 - 148. doi:10.1016/j.semcdb.2014.11.001
    • Vitiello E, Ferreira JG, Maiato H, Balda MS, Matter K (2014). The tumour suppressor DLC2 ensures mitotic fidelity by coordinating spindle positioning and cell-cell adhesion.. Nat Commun, 5, 5826 - . doi:10.1038/ncomms6826

    2013

    • Zihni C, Munro PM, Elbediwy A, Keep NH, Terry SJ, Harris J, Balda MS, Matter K (2013). An Ezrin/Dbl3 Complex Drives Cdc42 Signalling at the Vertebrate Marginal Zone to Regulate Junction Position and Epithelial Differentiation. MOLECULAR BIOLOGY OF THE CELL, 24, - .
    • Zihni C, Munro PM, Elbediwy A, Keep NH, Terry SJ, Harris J, Balda MS, Matter K (2013). An Ezrin/Dbl3 Complex Drives Cdc42 Signalling at the Vertebrate Marginal Zone to Regulate Junction Position and Epithelial Differentiation. MOLECULAR BIOLOGY OF THE CELL, 24, - .
    • Vitiello E, Ferreira J, Maiato H, Balda MS, Matter K (2013). DLC2 temporally regulates Cdc42 to satisfy the mitotic checkpoint and prevent aneuploidy. MOLECULAR BIOLOGY OF THE CELL, 24, - .

    2012

    • Terry SJ, Elbediwy A, Zihni C, Harris A, Bailly M, Charras G, Balda M, Matter K (2012). Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion. PLoS One, In press, - .
    • Nie M, Balda MS, Matter K (2012). Stress- and Rho-activated ZO-1-associated nucleic acid binding protein binding to p21 mRNA mediates stabilization, translation, and cell survival.. Proc Natl Acad Sci U S A, 109(27), 10897 - 10902. doi:10.1073/pnas.1118822109
    • Elbediwy A, Zihni C, Terry SJ, Clark P, Matter K, Balda MS (2012). Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex.. J Cell Biol, 198(4), 677 - 693. doi:10.1083/jcb.201202094
    • Vitiello E, Balda M, Matter K (2012). Regulation of microtubule attachment at kinetochores and cell cortex by Cdc42.. MOLECULAR BIOLOGY OF THE CELL, 23, - .

    2011

    • Grieve AG, Daniels RD, Sanchez-Heras E, Hayes MJ, Moss SE, Matter K, Lowe M, Levine TP (2011). Lowe Syndrome protein OCRL1 supports maturation of polarized epithelial cells.. PLoS One, 6(8), e24044 - . doi:10.1371/journal.pone.0024044
    • Chakarova CF, Khanna H, Shah AZ, Patil SB, Sedmak T, Murga-Zamalloa CA, Papaioannou MG, Nagel-Wolfrum K, Lopez I, Munro P, Cheetham M, Koenekoop RK, Rios RM, Matter K, Wolfrum U, Swaroop A, Bhattacharya SS (2011). TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein.. Hum Mol Genet, 20(5), 975 - 987. doi:10.1093/hmg/ddq543
    • Terry SJ, Zihni C, Elbediwy A, Vitiello E, Leefa Chong San IV, Balda MS, Matter K (2011). Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis.. Nat Cell Biol, 13(2), 159 - 166. doi:10.1038/ncb2156

    2010

    • Steed E, Balda MS, Matter K (2010). Dynamics and functions of tight junctions. Trends in Cell Biology, , - . doi:10.1016/j.tcb.2009.12.002
    • Georgiadis A, Tschernutter M, Bainbridge JW, Balaggan KS, Mowat F, West EL, Munro PM, Thrasher AJ, Matter K, Balda MS, Ali RR (2010). The tight junction associated signalling proteins ZO-1 and ZONAB regulate retinal pigment epithelium homeostasis in mice.. PLoS One, 5(12), e15730 - . doi:10.1371/journal.pone.0015730
    • Larre I, Lazaro A, Contreras RG, Balda MS, Matter K, Flores-Maldonado C, Ponce A, Flores-Benitez D, Rincon-Heredia R, Padilla-Benavides T, Castillo A, Shoshani L, Cereijido M (2010). Ouabain modulates epithelial cell tight junction.. Proc Natl Acad Sci U S A, 107(25), 11387 - 11392. doi:10.1073/pnas.1000500107
    • Lima WR, Parreira KS, Devuyst O, Caplanusi AN, Kuli F, Marien B, Smissen PV, Alves PM, Verroust P, Christensen EI, Terzi F, Matter K, Balda MS, Pierreux CE, Courtoy PJ (2010). ZONAB Promotes Proliferation and Represses Differentiation of Proximal Tubule Epithelial Cells. Journal of the American Society of Nephrology, 21, 478 - 488. doi:10.1681/ASN.2009070698
    • Tsapara A, Luthert P, Greenwood J, Hill CS, Matter K, Balda MS (2010). The RhoA Activator GEF-H1/Lfc Is a TGF-β Target Gene and Effector that Regulates α-Smooth Muscle Actin Expression and Cell Migration. Molecular Biology of the Cell, , - . doi:10.1091/mbc.E09-07-0567
    • Terry S, Nie M, Matter K, Balda MS (2010). Rho signaling and tight junction functions. Physiology, 25, 16 - 26. doi:10.1152/physiol.00034.2009

    2009

    • Abouhamed M, Grobe K, San IV, Thelen S, Honnert U, Balda MS, Matter K, Bähler M (2009). Myosin IXa regulates epithelial differentiation and its deficiency results in hydrocephalus. Molecular Biology of the Cell, 20, 5074 - 5085. doi:10.1091/mbc.E09-04-0291
    • Matter K, Balda MS (2009). SIGNALLING AT TIGHT JUNCTIONS AND REGULATION OF GENE EXPRESSION IN EPITHELIAL CELLS.
    • Harten SK, Shukla D, Barod R, Hergovich A, Balda MS, Matter K, Esteban MA, Maxwell PH (2009). Regulation of renal epithelial tight junctions by the von Hippel-Lindau tumor suppressor gene involves occludin and claudin 1 and is independent of E-cadherin.. Mol Biol Cell, 20(3), 1089 - 1101. doi:10.1091/mbc.E08-06-0566
    • Steed E, Rodrigues NT, Balda MS, Matter K (2009). Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family. BMC Cell Biology, 10, 95 - .
    • Nie M, Aijaz A, Leefa Chong San IV, Balda MS, Matter K (2009). The Y-box factor ZONAB/DbpA associates with GEF-H1/Lfc and mediates Rho-stimulated transcription. EMBO Report, 10, 1125 - 1131.
    • Harten SK, Shukla D, Barod R, Hergovich A, Balda MS, Matter K, Esteban MA, Maxwell PH (2009). Regulation of renal epithelial tight junctions by the von Hippel-Lindau tumor suppressor gene involves occludin and claudin 1 and is independent of E-cadherin. Mol.Biol.Cell, 20(3), 1089 - 1101. doi:10.1091/mbc.E08-06-0566
    • Balda MS, Matter K (2009). Tight junctions and the regulation of gene expression. Biochim.Biophys.Acta, 1788(4), 761 - 767. doi:10.1016/j.bbamem.2008.11.024

    2008

    • Balda MS, Matter K (2008). Tight junctions at a glance. J.Cell Sci., 121(Pt 22), 3677 - 3682.

    2007

    • Pannequin J, Delaunay N, Darido C, Maurice T, Crespy P, Frohman MA, Balda MS, Matter K, Joubert D, Bourgaux JF, Bali JP, Hollande F (2007). Phosphatidylethanol accumulation promotes intestinal hyperplasia by inducing ZONAB-mediated cell density increase in response to chronic ethanol exposure. Mol.Cancer Res., 5(11), 1147 - 1157.
    • Chakarova CF, Papaioannou MG, Khanna H, Lopez I, Waseem N, Shah A, Theis T, Friedman J, Maubaret C, Bujakowska K, Veraitch B, Abd El-Aziz MM, Prescott Q, Parapuram S, Bickmore WA, Munro PMG, Gal A, Hamel CP, Marigo V, Ponting CP, Wissinger B, Zrenner E, Matter K, Swaroop A, Koenekoop RK, Bhattacharya SS (2007). Mutations in TOPORS Cause Autosomal Dominant Retinitis Pigmentosa with Perivascular RPE Atrophy. The American Journal of Human Genetics, 81(5), 1098 - 1103. doi:10.1086/521953
    • Aijaz S, Sanchez-Heras E, Balda MS, Matter K (2007). Regulation of tight junction assembly and epithelial morphogenesis by the heat shock protein Apg-2. BMC.Cell Biol., 8, 49 - .
    • Matter K, Balda MS (2007). Epithelial tight junctions, gene expression and nucleo-junctional interplay. J.Cell Sci., 120(Pt 9), 1505 - 1511.

    2006

    • Aijaz S, Balda MS, Matter K (2006). Tight junctions: molecular architecture and function. International Review of Cytology, 248, 261 - 298.
    • Sourisseau T, Georgiadis A, Tsapara A, Ali RR, Pestell R, Matter K, Balda MS (2006). Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1 regulated transcription factor ZONAB/DbpA. Molecular and Cellular Biology, 26(6), 2387 - 2398. doi:10.1128/MCB.26.6.2387-2398.2006
    • Castagner F, Atanasoski S, Balda M, Matter K, Suter U (2006). Role of dbpA in neural crest and Schwarm cell development. doi:10.1016/j.ijdevneu.2006.09.099
    • Tsapara A, Matter K, Balda MS (2006). The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB. Molecular Biology of the Cell, 17(3), 1322 - 1330. doi:10.1091/mbc.E05-06-0507
    • Kavanagh E, Buchert M, Tsapara A, Choquet A, Balda MS, Hollande F, Matter K (2006). Functional interaction between the ZO-1-interacting transcription factor ZONAB/DbpA and the RNA processing factor symplekin. Journal of cell science, 119(Pt 24), 5098 - 5105. doi:10.1242/jcs.03297

    2005

    • Matter K, Aijaz S, Tsapara A, Balda MS (2005). Mammalian tight junctions in the regulation of epithelial differentiation and proliferation. Current opinion in cell biology, 17(5), 453 - 458. doi:10.1016/j.ceb.2005.08.003
    • Aijaz S, D'Atri F, Citi S, Balda MS, Matter K (2005). Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1/S phase transition. Developmental Cell, 8(5), 777 - 786. doi:10.1016/j.devcel.2005.03.003
    • Shoshani L, Contreras RG, Roldan ML, Moreno J, Lazaro A, Balda MS, Matter K, Cereijido M (2005). The polarized expression of Na+,K+-ATPase in epithelia depends on the association between beta-subunits located in neighboring cells. Molecular Biology of the Cell, 16(3), 1071 - 1081. doi:10.1091/mbc.E04-03-0267
    • Frankel P, Aronheim A, Kavanagh E, Balda MS, Matter K, Bunney TD, Marshall CJ (2005). RalA interacts with ZONAB in a cell density-dependent manner and regulates its transcriptional activity. The EMBO Journal, 24(1), 54 - 62. doi:10.1038/sj.emboj.7600497
    • Limb GA, Matter K, Murphy G, Cambrey AD, Bishop PN, Morris GE, Khaw PT (2005). Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis. American Journal of Pathology, 166(5), 1555 - 1563.

    2004

    • Aijaz S, Goodrick S, Matter K, Balda MS (2004). Tight Junctions. In Ganden D, Ruckpaul K (Ed.), Encyclopaedic References of Genomes and Proteomics in Molecular Medicine (pp. - ). : Springer-Verlag International.
    • Shoshani L, Contreras RG, Roldan ML, Moreno J, Lazaro A, Balda MS, Matter K, Cereijido M (2004). The polarized expression of NA+,K+-ATPase in epithelia depends on the association between beta-subunits located in neighboring cells.

    2003

    • Balda MS, Garrett MD, Matter K (2003). The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density. The Journal of Cell Biology, 160(3), 423 - 432. doi:10.1083/jcb.200210020
    • Matter K, Balda MS (2003). Signalling to and from tight junctions. Nature Reviews Molecular Cell Biology, 4(3), 225 - 236. doi:10.1038/nrm1055
    • Balda MS, Greenwood J, Adamson P, Matter K (2003). Differentiation of retinal pigment epithelium: The role of the tight junction associated transcription factor ZONAB.
    • Chapple JP, Grayson C, Hardcastle AJ, Bailey TA, Matter K, Adamson P, Graham CH, Willison KR, Cheetham ME (2003). Organization on the plasma membrane of the retinitis pigmentosa protein RP2: investigation of association with detergent-resistant membranes and polarized sorting. Biochemical Journal, 372(Pt 2), 427 - 433.
    • Matter K, Balda MS (2003). Holey barrier: claudins and the regulation of brain endothelial permeability. The Journal of Cell Biology, 161(3), 459 - 460.
    • Benais-Pont G, Punn A, Flores-Maldonado C, Eckert J, Raposo G, Fleming TP, Cereijido M, Balda MS, Matter K (2003). Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability. The Journal of Cell Biology, 160(5), 729 - 740. doi:10.1083/jcb.200211047
    • Matter K, Balda MS (2003). Functional analysis of tight junctions. Methods, 30(3), 228 - 234.
    • Balda MS, Matter K (2003). Epithelial cell adhesion and the regulation of gene expression. Trends in Cell Biology, 13(6), 310 - 318. doi:10.1016/S0962-8924(03)00105-3

    2001

    • Matter K, Balda MS (2001). Tight junctions and the differentiation of polarized epithelia.
    • Pont-Benais G, Matter K, Balda MS (2001). Intracellular signalling in classical and new tight junction functions. In Cereijido M, Anderson JM (Ed.), Tight junctions (pp. 367 - 394). : CRC Press.