Faculty of Biological Sciences

Dr Martin Stacey

MBiochem, Oxford; DPhil, Oxford, PhD - 2001
Lecturer in Immunology
School of Molecular and Cellular Biology

Contact:  Garstang 8.53a, +44(0) 113 34 33145, email address for  

Research Interests

Understanding the role of phagocytes at the cellular and molecular level

Our research interests focus on how cell surface receptors of myeloid cells influence the activities of phagocytic cells such as macrophages, neutrophils and dendritic cell in inflammatory and infectious diseases.   In particular we are characterising the role and function of a family of predominantly myeloid restricted receptors known as EGF-TM7 receptors (see figure below).  These unusual receptors as defined by their unique chimaeric structure in which EGF-like domains are coupled to a G protein-coupled receptor moiety via a critical stalk region.  Using a novel ligand screening strategy we have previously shown these receptors have a variety of cell surface and matrix ligands and demonstrated them to be involved in cellular signalling and cell migration. We have also demonstrated that these receptors undergo an autocatalytic proteolytic event within their stalk region that is essential for receptor signalling.

Our present research goals include:

  • Isolation of exogenous ligands for EGF-TM7 receptors
  • Characterisation of downstream signalling events
  • Generation of recombinant antibodies for targeting myeloid cells

EGF-TM7 family diagram

 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Generation of recombinant immunotoxins for targeting phagocytes. Key techniques: Molecular Biology, including PCR, cloning, Western blotting and protein purification; Cellular Biology, including tissue culture, FACS analysis and confocal microscopy
  • Characterisation of microbial ligands for myeloid receptors. Key techniques: Protein chemistry and molecular biology including protein expression, isolation and purification. Ligand screening assays, FACS analysis

Postgraduate studentship areas:

  • Leukocyte receptors in cancer progression
  • Generation of immunotoxins for targeting myeloid cells
  • Understanding macrophage and neutrophil signalling

See also:

Modules managed

BIOL1214 - Multicellular Systems
BIOL5146M - Advanced Immunology
FOBS1201 - Molecular Physiology
MICR1220 - Introduction to Immunology
MICR2221 - Medical Immunology

Modules taught

BIOC2301 - Intermediate Integrated Biochemistry
BIOC3111/12/BIOL3112/MICR3120/BIOL5146M a - ATU - Innate immunity
BIOL1302 - Introductory Skills for Biological Sciences
BIOL1302/1303/MICR1320 - Intro skills - Biological Science and Microbiology
BIOL1305 - Integrated Skills in Biosciences 1
BIOL2301 - Intermediate Skills for Biological Sciences
BIOL2301/03/MICR2320/BIOL3400 - BIOL/BIOC/MICR advanced skills/Skills in the Cell Biology of Human Disease
BIOL3306 - Biological Sciences Research Project
BIOL3398 - Research Tools and Applications
BIOL3399 - Extended Research Project Preparation
BIOL5146M - Advanced Immunology
BIOL5294M - MSc Bioscience Research Project Proposal
BIOL5392M - Bioscience MSc Research Project
FOBS1201/BIOL1214 - Molecular Physiology/Multicellular Systems
FOBS1201/MICR1220 - Molecular Physiology/Introduction to Immunology
MICR1201 - Introduction to Microbiology
MICR1220 - Introduction to Immunology
MICR2120/BIOC2301 - Integrated Biochemistry/Medical Bacteriology
MICR2221 - Medical Immunology
MICR3110 - Medical Microbiology Research Project
MICR3325 - Skills for Microbiologists 3

Committees

Member of Graduate School Committee (Admissions Tutor (MCB))

Group Leader Dr Martin Stacey  (Lecturer in Immunology)

Understanding the role of phagocytes at the cellular and molecular level 

Postgraduates

Rebecca Holdich (Primary supervisor) 70% FTE
Anna Keszegpal (Co-supervisor) 35% FTE
Thomas Macleod (Co-supervisor) 50% FTE
Sharifah Alawieyah Syed Mortadza (Co-supervisor) 25% FTE

Bridgewood C, Stacey M, Alase A, Lagos D, Graham A, Wittmann M IL-36γ has proinflammatory effects on human endothelial cells. Exp Dermatol 26 402-408, 2017
DOI:10.1111/exd.13228
View abstract

I K-Y, Huang Y-S, Hu C-H, Tseng W-Y, Cheng C-H, Stacey M, Gordon S, Chang G-W, Lin H-H Activation of Adhesion GPCR EMR2/ADGRE2 Induces Macrophage Differentiation and Inflammatory Responses via Gα16/Akt/MAPK/NF-κB Signaling Pathways Frontiers in Immunology 8 -, 2017
DOI:10.3389/fimmu.2017.00373

Ainscough JS, MacLeod T, McGonagle D, Brakefield R, Baron JM, Alase A, Wittmann M, Stacey M Cathepsin S is the major activator of the psoriasisassociated proinflammatory cytokine IL-36γ Proceedings of the National Academy of Sciences of the United States of America 114 E2748-E2757, 2017
DOI:10.1073/pnas.1620954114
View abstract

Mortadza SS, Sim JA, Stacey M, Jiang LH Signalling mechanisms mediating Zn 2+ -induced TRPM2 channel activation and cell death in microglial cells Scientific Reports 7 -, 2017
DOI:10.1038/srep45032
View abstract

Macleod T, Ainscough J, Alase A, Stacey M, Wittmann M Skin and neutrophil derived proteases regulate the activity of IL-36 family members, 2017

Lin HH, Stacey M G Protein-Coupled Receptors in Macrophages Microbiology Spectrum 4 -, 2016
DOI:10.1128/microbiolspec.MCHD-0028-2016

Macleod T, Doble R, McGonagle D, Wasson CW, Alase A, Stacey M, Wittmann M Neutrophil Elastase-mediated proteolysis activates the anti-inflammatory cytokine IL-36 Receptor antagonist. Sci Rep 6 24880-, 2016
DOI:10.1038/srep24880
View abstract

Efimov GA, Kruglov AA, Khlopchatnikova ZV, Rozov FN, Mokhonov VV, Rose-John S, Scheller J, Gordon S, Stacey M, Drutskaya MS, Tillib SV, Nedospasov SA Cell-type-restricted anti-cytokine therapy: TNF inhibition from one pathogenic source Proceedings of the National Academy of Sciences of the United States of America 113 3006-3011, 2016
DOI:10.1073/pnas.1520175113
View abstract

Lewis SM, Treacher DF, Edgeworth J, Mahalingam G, Brown CS, Mare TA, Stacey M, Beale R, Brown KA Expression of CD11c and EMR2 on neutrophils: Potential diagnostic biomarkers for sepsis and systemic inflammation Clinical and Experimental Immunology 182 184-194, 2015
DOI:10.1111/cei.12679
View abstract

Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T, Schiöth HB International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol Rev 67 338-367, 2015
DOI:10.1124/pr.114.009647
View abstract

Araç D, Aust G, Calebiro D, Engel FB, Formstone C, Goffinet A, Hamann J, Kittel RJ, Liebscher I, Lin HH, Monk KR, Petrenko A, Piao X, Prömel S, Schiöth HB, Schwartz TW, Stacey M, Ushkaryov YA, Wobus M, Wolfrum U, Xu L, Langenhan T Dissecting signaling and functions of adhesion G protein-coupled receptors. Ann N Y Acad Sci 1276 1-25, 2012
DOI:10.1111/j.1749-6632.2012.06820.x
View abstract

Huang Y-S, Chiang N-Y, Hu C-H, Hsiao C-C, Cheng K-F, Tsai W-P, Yona S, Stacey M, Gordon S, Chang G-W, Lin H-H Activation of Myeloid Cell-Specific Adhesion Class G Protein-Coupled Receptor EMR2 via Ligation-Induced Translocation and Interaction of Receptor Subunits in Lipid Raft Microdomains MOLECULAR AND CELLULAR BIOLOGY 32 1408-1420, 2012
DOI:10.1128/MCB.06557-11

Stacey MJ, Huang YS Activation of myeloid-specific adhesion-GPCR EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol Cell Biol -, 2012
DOI:10.1128/​MCB.06557-11

Li J, McKeown L, Ojelabi O, Stacey M, Foster R, O'Regan D, Porter KE, Beech DJ Nanomolar potency and selectivity of a Ca²⁺ release-activated Ca²⁺ channel inhibitor against store-operated Ca²⁺ entry and migration of vascular smooth muscle cells. Br J Pharmacol 164 382-393, 2011
DOI:10.1111/j.1476-5381.2011.01368.x
View abstract

Gordon S, Hamann J, Lin HH, Stacey M F4/80 and the related adhesion-GPCRs. Eur J Immunol 41 2472-2476, 2011
DOI:10.1002/eji.201141715
View abstract

Gordon S, Hamann J, Lin HH, Stacey M Cover picture: eur. J. Immunol. 9/11. Eur J Immunol 41 -, 2011
DOI:10.1002/eji.201190056
View abstract

Li J, Cubbon RM, Wilson LA, Amer MS, McKeown L, Hou B, Majeed Y, Tumova S, Seymour VAL, Taylor H, Stacey M, O'Regan D, Foster R, Porter KE, Kearney MT, Beech DJ Orai1 and CRAC Channel Dependence of VEGF-Activated Ca2+ Entry and Endothelial Tube Formation CIRC RES 108 1190-U131, 2011
DOI:10.1161/CIRCRESAHA.111.243352

Davies JQ, Lin HH, Stacey M, Yona S, Chang GW, Gordon S, Hamann J, Campo L, Han C, Chan P, Fox SB Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival ONCOL REP 25 619-627, 2011
DOI:10.3892/or.2010.1117

Rosas M, Thomas B, Stacey M, Gordon S, Taylor PR The myeloid 7/4-antigen defines recently generated inflammatory macrophages and is synonymous with Ly-6B J LEUKOCYTE BIOL 88 169-180, 2010
DOI:10.1189/jlb.0809548

Lin HH, Stacey M, Yona S, Chang GW GPS PROTEOLYTIC CLEAVAGE OF ADHESION-GPCRs ADV EXP MED BIOL 706 49-58, 2010

Yona S, Lin HH, Stacey M IMMUNITY AND ADHESION-GPCRs ADV EXP MED BIOL 706 121-127, 2010

Lin HH, Stacey M, Stein-Streilein J, Gordon S F4/80: The Macrophage-Specific Adhesion-GPCR and its Role in Immunoregulation ADV EXP MED BIOL 706 149-156, 2010

Yona S, Stacey M MAMMALIAN ADHESION-GPCRs ADV EXP MED BIOL 706 189-193, 2010

Hsiao CC, Cheng KF, Chen HY, Chou YH, Stacey M, Chang GW, Lin HH Site-specific N-glycosylation regulates the GPS auto-proteolysis of CD97 FEBS LETT 583 3285-3290, 2009
DOI:10.1016/j.febslet.2009.09.001

Lin HH, Chang GW, Huang YS, Hsiao CC, Stacey MJ, Gordon S Multivalent Protein Probes for the Identification and Characterization of Cognate Cellular Ligands for Myeloid Cell Surface Receptors Methods Mol Biol 89-101, 2009
DOI:10.1007/978-1-59745-396-7_7
View abstract

Yona S, Lin HH, Siu WO, Gordon S, Stacey M Adhesion-GPCRs: emerging roles for novel receptors TRENDS BIOCHEM SCI 33 491-500, 2008
DOI:10.1016/j.tibs.2008.07.005

Cordle J, Redfield C, Stacey M, van der Merwe PA, Willis AC, Champion BR, Hambleton S, Handford PA Localization of the delta-like-1-binding site in human notch-1 and its modulation by calcium affinity J BIOL CHEM 283 11785-11793, 2008

Yona S, Lin HH, Dri P, Davies JQ, Hayhoe RPG, Lewis SM, Heinsbroek SEM, Brown KA, Perretti M, Hamann J, Treacher DF, Gordon S, Stacey M Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function FASEB J 22 741-751, 2008
DOI:10.1096/fj.07-9435com

Hamann J, Koning N, Pouwels W, Ulfman LH, van Eijk M, Stacey M, Lin HH, Gordon S, Kwakkenbos MJ EMR1, the human homolog of F4/80, is an eosinophil-specific receptor EUR J IMMUNOL 37 2797-2802, 2007
DOI:10.1002/eji.200737553

Davies JQ, Chang GW, Yona S, Gordon S, Stacey M, Lin HH The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors J BIOL CHEM 282 27343-27353, 2007
DOI:10.1074/jbc.M704096200

Chang GW, Davies JQ, Stacey M, Yona S, Bowdish DME, Hamann J, Chen TC, Lin CY, Gordon S, Lin HH CD312, the human adhesion-GPCR EMR2, is differentially expressed during differentiation, maturation, and activation of myeloid cells BIOCHEM BIOPH RES CO 353 133-138, 2007
DOI:10.1016/j.bbrc.2006.11.148

Capasso M, Durrant LG, Stacey M, Gordon S, Ramage J, Spendlove I Costimulation via CD55 on human CD4(+) T cells mediated by CD97 J IMMUNOL 177 1070-1077, 2006

Lin HH, Faunce DE, Stacey M, Terajewicz A, Nakamura T, Zhang-Hoover J, Kerley M, Mucenski ML, Gordon S, Stein-Streilein J The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance J EXP MED 201 1615-1625, 2005
DOI:10.1084/jem.20042307

Lin HH, Stacey M, Chang GW, Davies JQ, Gordon S Method for selecting and enriching cells expressing low affinity ligands for cell surface receptors BIOTECHNIQUES 38 696-+, 2005

Kop EN, Kwakkenbos MJ, Teske GJD, Kraan MC, Smeets TJ, Stacey M, Lin HH, Tak PP, Hamann J Identification of the epidermal growth factor-TM7 receptor EMR2 and its ligand dermatan sulfate in rheumatoid synovial tissue ARTHRITIS RHEUM 52 442-450, 2005
DOI:10.1002/art.20788

Taylor PR, Martinez-Pomares L, Stacey M, Lin HH, Brown GD, Gordon S Macrophage receptors and immune recognition. Annu Rev Immunol 23 901-944, 2005
DOI:10.1146/annurev.immunol.23.021704.115816
View abstract

Kwakkenbos MJ, Pouwels W, Matmati M, Stacey M, Lin HH, Gordon S, van Lier RAW, Hamann J Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells J LEUKOCYTE BIOL 77 112-119, 2005
DOI:10.1189/jlb.0704402

Lin HH, Chang GW, Davies JQ, Stacey M, Harris J, Gordon S Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif. J Biol Chem 279 31823-31832, 2004
DOI:10.1074/jbc.M402974200
View abstract

Kwakkenbos MJ, Kop EN, Stacey M, Matmati M, Gordon S, Lin HH, Hamann J The EGF-TM7 family: a postgenomic view IMMUNOGENETICS 55 655-666, 2004
DOI:10.1007/s00251-003-0625-2

Stacey M, Chang GW, Davies JQ, Kwakkenbos MJ, Sanderson RD, Hamann J, Gordon S, Lin HH The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood 102 2916-2924, 2003
DOI:10.1182/blood-2002-11-3540
View abstract

Chang GW, Stacey M, Kwakkenbos MJ, Hamann J, Gordon S, Lin HH Proteolytic cleavage of the EMR2 receptor requires both the extracellular stalk and the GPS motif FEBS LETT 547 145-150, 2003
DOI:10.1016/S0014-5793(03)00695-1

Stacey M, Chang GW, Sanos SL, Chittenden LR, Stubbs L, Gordon S, Lin HH EMR4, a novel epidermal growth factor (EGF)-TM7 molecule up-regulated in activated mouse macrophages, binds to a putative cellular ligand on B lymphoma cell line A20 J BIOL CHEM 277 29283-29293, 2002
DOI:10.1074/jbc.M204306200

Wreschner DH, McGuckin MA, Williams SJ, Baruch A, Yoeli M, Ziv R, Okun L, Zaretsky J, Smorodinsky N, Keydar I, Neophytou P, Stacey M, Lin HH, Gordon S Generation of ligand-receptor alliances by "SEA" module-mediated cleavage of membrane-associated mucin proteins PROTEIN SCI 11 698-706, 2002
DOI:10.1110/ps.16502

Lin HH, Stacey M, Saxby C, Knott V, Chaudhry Y, Evans D, Gordon S, McKnight AJ, Handford P, Lea S Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions - Dissection of the CD97-CD55 complex J BIOL CHEM 276 24160-24169, 2001

Stacey M, Lin HH, Hilyard KL, Gordon S, McKnight AJ Human epidermal growth factor (EGF) module-containing mucin-like hormone receptor 3 is a new member of the EGF-TM7 family that recognizes a ligand on human macrophages and activated neutrophils. J Biol Chem 276 18863-18870, 2001
DOI:10.1074/jbc.M101147200
View abstract

Lin HH, Stacey M, Hamann J, Gordon S, McKnight AJ Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97 GENOMICS 67 188-200, 2000
DOI:10.1006/geno.2000.6238

Stacey M, Lin HH, Gordon S, McKnight AJ LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors. Trends Biochem Sci 25 284-289, 2000
View abstract