David Bryant - Molecular Control of Epithelial Polarity

Introduction

BryantD

Cells of many tissues are polarised, collectively forming configurations tailored to the needs of a tissue. A common feature of most cancers of epithelial origin is the loss of normal tissue architecture. Despite advances in identifying signalling pathways and genetic alterations involved in driving cancer progression, little is known about this very basic, yet fundamental question: how do such changes affect cell polarity to turn highly organised tissues into disarrayed tumours?

bryant model of polarity

Our lab focuses on how cell polarity is controlled in prostate tumours. Our efforts are focused on two molecular pathways: the role of ARF GTPases (and their regulators and effectors, which we call the 'ARF regulome'), and the role of the cell surface protein, Podocalyxin. Both molecules are highly overexpressed in metastatic prostate cancer tumours.

We have developed cutting-edge, high-content microscopy and computational image analysis of tumour spheroids and organoids to characterise how cell polarity is altered from normal cells to become tumours. Our ultimate aim is to investigate such changes in cell polarity as potential future biomarkers of cancer in patients, and possible targets for future therapeutic interventions.


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Other funding:

    CRUK Glasgow Centre       Royal Society logo  

Lab Report

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Research Highlights

  • Extensive molecular characterisation of how cells know to orient their apical surfaces in the correct direction. Importantly, this work uncovers one way by which the extracellular matrix determines whether groups of epithelial cells become invasive or form a lumen (Dev Cell 2014)
  • Molecular characterisation of how cell polarity rearrangements can function as an innate response system of epithelial barriers to a bacterial pathogen challenge (p. aeruginosa) (Cell Host Microbe 2014)
  • First molecular description of the membrane trafficking and polarity rearrangements required to form an apical surface and lumen de novo. Our findings have been recapitulated in many other systems, showing that we uncovered a fundamentally conserved biological process (Nat Cell Biol 2012)
  • Discovery of an unexpected role of the EGF receptor in controlling basolateral to apical transport of vesicles. Key to this work was a novel cascade of kinases leading to the vesicle transport protein Rab11FIP5 (Nat Cell Biol 2012)
  • The elucidation of how multiple trafficking GTPases can function with the same effector (Myosin-5B) to control the function of the apical membrane and lumen (PNAS 2011)

Key Recent Publications

Bryant DM, Roignot J, Datta A, Overeem AW, Kim M, Yu W, Peng X, Eastburn DJ, Ewald AJ, Werb Z, Mostov KE. A molecular switch for the orientation of epithelial cell polarization. Dev Cell, Epub 9 Oct 2014 DOI: http://dx.doi.org/10.1016/j.devcel.2014.08.027

Tran CS, Eran Y, Ruch TR, Bryant DM, Datta A, Brakeman P, Kierbel A, Wittmann T, Metzger RJ, Mostov KE, Engel JN. Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection. Cell Host Microbe 15: 636-43, 2014

Lepanto P, Bryant DM, Rossello J, Datta A, Mostov KE, Kierbel A. Pseudomonas aeruginosa interacts with epithelial cells rapidly forming aggregates that are internalized by a Lyn-dependent mechanism. Cell Micro 13: 1212-22, 2011

Roland, JT*, Bryant, DM*, Datta, A, Itzen, A, Mostov, KE, Goldenring, JR. Rab GTPase-Myo5B complexes control membrane recycling and epithelial polarization. PNAS 108: 2789-94, 2011

Su T, Bryant DM, Luton F, Vergés M, Ulrich SM, Hansen KC, Datta A, Eastburn DJ, Burlingame AL, Shokat KM, Mostov KE. A kinase cascade leading to Rab11-FIP5 controls transcytosis of the polymeric immunoglobulin receptor. Nat Cell Biol 12: 1143-53, 2010

Bryant DM, Datta A, Rodríguez-Fraticelli AE, Peränen J, Martín-Belmonte F, Mostov KE. A molecular network for de novo generation of the apical surface and lumen. Nat Cell Biol 12: 1035-45, 2010

Biography

Education and qualifications

2006: PhD, University of Queensland, Australia, Supervisor Jennifer Stow
2002: BSc (Hons) Class I, University of Queensland, Australia

Appointments

2014-present: Senior Lecturer/Beatson Associate, University of Glasgow
2012-2014: Associate Academic Researcher, University of California, San Francisco, USA
2006-2012: Postdoctoral Fellow with Keith Mostov, UC San Francisco, USA

Recent Publications

2018

Stehbens SJ, Ju RJ, Adams MN, Perry S, Haass NK, Bryant DM, Pollock PM. FGFR2b activating mutations disrupt cell polarity to potentiate migration and invasion in endometrial cancer. J Cell Sci 2018 Jul 12. pii: jcs.213678. doi: 10.1242/jcs.213678. [Epub ahead of print]

2017

Datta A, Sandilands E, Mostov KE, Bryant DM. Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition. Cell Signal 2017; 40: 91-8

Gao L, Yang Z, Hiremath C, Zimmerman SE, Long B, Brakeman PR, Mostov KE, Bryant DM, Luby-Phelps K, Marciano DK. Afadin orients cell division to position the tubule lumen in developing renal tubules. Development 2017; 144: 3511-20

Reid SE, Kay EJ, Neilson LJ, Henze AT, Serneels J, McGhee EJ, Dhayade S, Nixon C, Mackey JB, Santi A, Swaminathan K, Athineos D, Papalazarou V, Patella F, Roman-Fernandez A, ElMaghloob Y, Hernandez-Fernaud JR, Adams RH, Ismail S, Bryant DM et al. Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO J 2017; 36: 2373-89

Ruch TR, Bryant DM, Mostov KE, Engel JN. Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity. Mol Biol Cell 2017; 28: 252-60

Bryant D, Johnson A. Meeting report - Intercellular interactions in context: towards a mechanistic understanding of cells in organs. J Cell Sci 2017; 130: 2083-85

2016

Yang Z, Zimmerman SE, Tsunezumi J, Braitsch C, Trent C, Bryant DM, Cleaver O, Gonzalez-Manchon C, Marciano DK. Role of CD34 family members in lumen formation in the developing kidney. Dev Biol 418: 66-74, 2016

Bryant DM, Yap AS. Editorial overview: Membrane traffic and cell polarity. Traffic 17: 1231-2, 2016

Roman-Fernandez A, Bryant DM. Complex polarity: Building multicellular tissues through apical membrane traffic. Traffic 17: 1244-61, 2016

2015

Overeem AW, Bryant DM, van ISC. Mechanisms of apical-basal axis orientation and epithelial lumen positioning. Trends Cell Biol 2015. Epub 2015/05/06

2014

Bryant DM, Roignot J, Datta A, Overeem AW, Kim M, Yu W, Peng X, Eastburn DJ, Ewald AJ, Werb Z, Mostov KE. A molecular switch for the orientation of epithelial cell polarization. Dev Cell 31: 171-87, 2014

Tran CS, Eran Y, Ruch TR, Bryant DM, Datta A, Brakeman P, Kierbel A, Wittmann T, Metzger RJ, Mostov KE, Engel JN. Host cell polarity proteins participate in innate immunity to Pseudomonas aeruginosa infection. Cell Host Microbe 15: 636-43, 2014

Lab Members

Bryant lab 071 cropped

Post-docs

Mohammed Mansour (Royal Society Newton International Fellowship)
Alvaro Roman Fernandez (University of Glasgow)

Scientific Officer

Emma Sandilands (University of Glasgow)

PhD Students

Eva Freckmann (University of Glasgow Industrial PhD Partnership)
Marisa Nacke (CRUK Glasgow Centre)
Konstantina Nikolatou (CRUK Glasgow Centre)
Narissa Parry

Research

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Seminars

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