Dr Heather L Wilson
BSc DPhil
Clinical Medicine, School of Medicine and Population Health
Senior Lecturer in Immunity & Cardiovascular Disease
+44 114 215 9560
Full contact details
Clinical Medicine, School of Medicine and Population Health
The Medical School
Beech Hill Road
Sheffield
S10 2RX
- Profile
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For enquiries, please contact - SMPH-West-Operational@sheffield.ac.uk
- Qualifications
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- BSc (First Class) in Pharmacology, University College London
- Research Scientist, Pharmacology Department, Wellcome Research Laboratories, Beckenham, Kent
- D.Phil. in Pharmacology, University of Oxford. Laboratory of Prof. Antony Galione
- Research interests
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My overarching research focus is to understand how immune activation is linked to heart disease. Following a severe infection like pneumonia, individuals are at a higher risk of heart attack or stroke for up to 3 weeks after the infection.
We believe this is because immune cells in the atherosclerotic plaque become activated by inflammation, making the plaque more prone to rupture. Macrophages are a key immune cell in the arterial plaque, that alter their response and cellular function when exposed to infection or inflammatory signals.
We have investigated how these atherosclerotic macrophages alter functionally according to their environment. Specifically we have addressed how P2X7 receptors, interleukin-1 secretion and Tribbles expression affect macrophage function.
We are currently also interested in understanding the function of adipose tissue macrophages, since different fat depots are more or less associated with inflammation and disease: abdominal fat is associated with cardiovascular diseases and cancer susceptibility, while peripheral fat confers a lower disease risk.
We work closely with cardiology and stroke consultants within IICD and the Medical School in Sheffield so that our basic science is connected to patient disease. We are also fortunate to be part of a European Commission funded International Training Network, where we connect with scientists across Europe who have complimentary interests to link immunity, metabolism and disease together. We are increasingly aware that obesity is connected to cancer risk as well as cardiovascular diseases, and seek to understand the underlying mechanisms.
Current projects
- Biotechnology and Biological Sciences Research Council Project Grant. "Novel zebrafish approaches to investigate leaderless protein secretion in vivo."
- British Heart Foundation Project Grant. "Mechanisms and consequences of in vivo targeting of IL-1 to the endothelium."
- British Heart Foundation PhD studentship. "Regulation of the Endothelial P2X4/7 Receptor Axis.”
- Heart Research UK. Clinical Training Fellowship (supervisor). "Neutrophil delivery of IL-1 as a mechanism of MI risk after lung infection."
- A*Star Studentship. "Contribution of blood immune cell subtypes in inflammatory function and the development of cardiovascular disease."
- Horizon 2020 European Commission. Marie Curie Innovative Training Network Programme Award. TRAIN ‘Tribbles Research and Innovation Network’ 2016-2021
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs. Cell Reports, 43(4), 114073-114073.
- The pseudokinase TRIB3 controls adipocyte lipid homeostasis and proliferation in vitro and in vivo. Molecular Metabolism, 78, 101829-101829.
- Markers of the ageing macrophage: a systematic review and meta-analysis. Frontiers in Immunology, 14. View this article in WRRO
- Tribbles 3 deficiency promotes atherosclerotic fibrous cap thickening and macrophage-mediated extracellular matrix remodelling. Frontiers in Cardiovascular Medicine, 9.
- Myeloid Tribbles 1 induces early atherosclerosis via enhanced foam cell expansion. Science Advances, 5(10), ---. View this article in WRRO
- TMEM203 is a binding partner and regulator of STING-mediated inflammatory signaling in macrophages. Proceedings of the National Academy of Sciences, 116(33), 16479-16488. View this article in WRRO
- tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis. Nature Communications, 10. View this article in WRRO
- Hif-1α–Induced Expression of Il-1β Protects against Mycobacterial Infection in Zebrafish. The Journal of Immunology, 202(2), 494-502. View this article in WRRO
- Atheroprone flow activates inflammation via endothelial ATP-dependent P2X7-p38 signalling. Cardiovascular Research, 114(2), 324-335. View this article in WRRO
- Regulating STING in health and disease. J Inflamm (Lond), 14, 11-11. View this article in WRRO
- Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability. Scientific Reports, 6. View this article in WRRO
- Neutrophil Elastase promotes Interleukin-1β secretion from Human Coronary Endothelium. Journal of Biological Chemistry, 290, 24067-24078. View this article in WRRO
- The IL-1 family in fish: swimming through the muddy waters of inflammasome evolution.. Dev Comp Immunol, 46(1), 53-62.
- Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response.. Dis Model Mech, 7(2), 259-264. View this article in WRRO
- Roles of neutrophils in the regulation of the extent of human inflammation through delivery of IL-1 and clearance of chemokines.. J Leukoc Biol, 93(1), 7-19. View this article in WRRO
- Temporal interleukin-1beta secretion from primary human peripheral blood monocytes by P2X7-independent and P2X7-dependent mechanisms.. J Biol Chem, 285(30), 23147-23158.
- Translational mini-review series on immunology of vascular disease: inflammation, infections and Toll-like receptors in cardiovascular disease.. Clin Exp Immunol, 156(3), 386-394.
- P2X receptor characterization and IL-1/IL-1Ra release from human endothelial cells.. Br J Pharmacol, 151(1), 115-127.
- Action of intracellular IL-1Ra (Type 1) is independent of the IL-1 intracellular signalling pathway.. Cytokine, 33(5), 274-280.
- Secretion of intracellular IL-1 receptor antagonist (type 1) is dependent on P2X7 receptor activation.. J Immunol, 173(2), 1202-1208.
All publications
Journal articles
- Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs. Cell Reports, 43(4), 114073-114073.
- The pseudokinase TRIB3 controls adipocyte lipid homeostasis and proliferation in vitro and in vivo. Molecular Metabolism, 78, 101829-101829.
- Markers of the ageing macrophage: a systematic review and meta-analysis. Frontiers in Immunology, 14. View this article in WRRO
- Tribbles 3 deficiency promotes atherosclerotic fibrous cap thickening and macrophage-mediated extracellular matrix remodelling. Frontiers in Cardiovascular Medicine, 9.
- Tribbles-1 expression and its function to control inflammatory cytokines, including interleukin-8 levels are regulated by miRNAs in macrophages and prostate cancer cells. Frontiers in Immunology, 11.
- Macrophage polarisation associated with atherosclerosis differentially affects their capacity to handle lipid. Atherosclerosis. View this article in WRRO
- Myeloid Tribbles 1 induces early atherosclerosis via enhanced foam cell expansion. Science Advances, 5(10), ---. View this article in WRRO
- microRNAs regulating Tribbles-1: potential molecular targets in prostate cancer. European Urology Supplements, 18(8), e3090-e3091.
- Macrophage-associated changes in peri-prostatic adipose tissue; a novel local driver of prostate tumorigenesis?. European Urology Supplements, 18(8), e3060-e3060.
- TMEM203 is a binding partner and regulator of STING-mediated inflammatory signaling in macrophages. Proceedings of the National Academy of Sciences, 116(33), 16479-16488. View this article in WRRO
- tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis. Nature Communications, 10. View this article in WRRO
- Hif-1α–Induced Expression of Il-1β Protects against Mycobacterial Infection in Zebrafish. The Journal of Immunology, 202(2), 494-502. View this article in WRRO
- P4 CONSEQUENCES OF TRIB3 DEFICIENCY ON EXPERIMENTAL ATHEROSCLEROSIS AND MACROPHAGE PHENOTYPE. Cardiovascular Research, 114(suppl_2), S2-S2.
- Atheroprone flow activates inflammation via endothelial ATP-dependent P2X7-p38 signalling. Cardiovascular Research, 114(2), 324-335. View this article in WRRO
- Regulating STING in health and disease. J Inflamm (Lond), 14, 11-11. View this article in WRRO
- Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability. Scientific Reports, 6. View this article in WRRO
- Identification of benzopyrone as a common structural feature in compounds with anti-inflammatory activity in a zebrafish phenotypic screen. DMM Disease Models and Mechanisms, 9, 621-632. View this article in WRRO
- Neutrophil Elastase promotes Interleukin-1β secretion from Human Coronary Endothelium. Journal of Biological Chemistry, 290, 24067-24078. View this article in WRRO
- Neutrophil elastase enhances IL-1 beta secretion from coronary endothelium via an endolysosomal mediated mechanism, without caspase-1 activation. ANGIOGENESIS, 17(4), 941-941.
- 213 Functional Characterisation of Monocyte Derived Macrophage Phenotypes for their Role in Atherosclerosis.. Heart, 100 Suppl 3, A117.
- The IL-1 family in fish: swimming through the muddy waters of inflammasome evolution.. Dev Comp Immunol, 46(1), 53-62.
- Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response.. Dis Model Mech, 7(2), 259-264. View this article in WRRO
- 2 IL-1B Secretion in Coronary Vascular Endothelium is Mediated by Neutrophil Serine Protease and is Independent of caspase-1.. Heart, 100 Suppl 1, A2.
- Roles of neutrophils in the regulation of the extent of human inflammation through delivery of IL-1 and clearance of chemokines.. J Leukoc Biol, 93(1), 7-19. View this article in WRRO
- Neutrophil Recruitment In Response To Intradermal Endotoxin Challenge In The Human. C34. NEUTROPHILS, MAST CELLS, BASOPHILS AND EOSINOPHILS IN LUNG DISEASE.
- Temporal interleukin-1beta secretion from primary human peripheral blood monocytes by P2X7-independent and P2X7-dependent mechanisms.. J Biol Chem, 285(30), 23147-23158.
- Translational mini-review series on immunology of vascular disease: inflammation, infections and Toll-like receptors in cardiovascular disease.. Clin Exp Immunol, 156(3), 386-394.
- P2X receptor characterization and IL-1/IL-1Ra release from human endothelial cells.. Br J Pharmacol, 151(1), 115-127.
- Action of intracellular IL-1Ra (Type 1) is independent of the IL-1 intracellular signalling pathway.. Cytokine, 33(5), 274-280.
- Secretion of intracellular IL-1 receptor antagonist (type 1) is dependent on P2X7 receptor activation.. J Immunol, 173(2), 1202-1208.
- Pharmacological and biophysical properties of the human P2X5 receptor.. Mol Pharmacol, 63(6), 1407-1416.
- Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus.. J Biol Chem, 277(37), 34017-34023.
- Proteomic and functional evidence for a P2X(7)receptor complex.. BIOPHYS J, 82(1), 254A-255A.
- Proteomic and functional evidence for a P2X7 receptor signalling complex.. EMBO J, 20(22), 6347-6358.
- Rapid secretion of interleukin-1beta by microvesicle shedding.. Immunity, 15(5), 825-835.
- ADP-ribosyl Cyclase and Cyclic ADP-ribose Hydrolase Act as a Redox Sensor. Journal of Biological Chemistry, 276(14), 11180-11188.
- Functional properties of heteromeric P2X(1/5) receptors expressed in HEK cells and excitatory junction potentials in guinea-pig submucosal arterioles.. J Auton Nerv Syst, 81(1-3), 249-263.
- Psammechinus miliaris egg homogenate as a model to investigate Ca2+-release mechanisms. Journal of the Marine Biological Association of the United Kingdom, 79(2), 323-326.
- Cyclic ADP-ribose and the regulation of calcium-induced calcium release in eggs and cardiac myocytes. Cell Biochemistry and Biophysics, 28(1), 19-30.
- Differential regulation of nicotinic acid–adenine dinucleotide phosphate and cADP-ribose production by cAMP and cGMP. Biochemical Journal, 331(3), 837-843.
- Characterization of a 5-HT1B receptor on CHO cells: functional responses in the absence of radioligand binding. British Journal of Pharmacology, 117(6), 1119-1126.
Conference proceedings papers
- BS80 Macrophage ATP8B1 is upregulated with age. Basic Science
- BS45 Transcription factors MYC and USF1 drive chronic macrophage dysfunction in ageing. Basic Science
- BS25 Investigating the MIR-101-3P/TRIB1 axis in macrophage immunometabolism. Basic Science
- Myeloid TRIB1 Controls Metabolic Tissue Resident Macrophage Phenotype Associated with Immuno-Metabolic Diseases. CARDIOVASCULAR DRUGS AND THERAPY, Vol. 33(2) (pp 271-271)
- P16 HUMAN MACROPHAGE SUBSETS IN THE PATHOGENESIS OF CAROTID ATHEROSCLEROSIS. Cardiovascular Research, Vol. 114(suppl_2) (pp S5-S6)
- CONSEQUENCES OF TRIB3 DEFICIENCY ON EXPERIMENTAL ATHEROSCLEROSIS AND MACROPHAGE PHENOTYPE. CARDIOVASCULAR RESEARCH, Vol. 114 (pp S2-S2)
- P26 MIR-101-3P CONTROLS TRIB1 EXPRESSION IN HUMAN MACROPHAGES: A POTENTIAL TARGET IN ATHEROSCLEROTIC PLAQUES. Cardiovascular Research, Vol. 114(suppl_2) (pp S8-S8)
- P14 MYELOID TRIB1 PROMOTES EXPERIMENTAL ATHEROSCLEROSIS. Cardiovascular Research, Vol. 114(suppl_2) (pp S4-S4)
- 114 TRIB3-mediated regulation of macrophage phenotype. Basic Science
- 110 Post-transcriptional regulation of trib1 by mirnas in primary macrophages. Basic Science
- 157 Myeloid expression of trib1 regulates the polarisation state of tissue resident macrophages that has consequences on plasma lipid and metabolic homeostasis. Heart, Vol. 103(Suppl 5) (pp A113.2-A113)
- 201 Human oxidised phospholipid macrophages have high lipoprotein handling capabilities without readily forming unwanted foam cells. Heart, Vol. 103(Suppl 5) (pp A136.1-A136)
- 191 Atheroprone Flow Alters ATP-Induced Calcium Signalling in the Endothelium. Heart, Vol. 102(Suppl 6) (pp A130.1-A130)
- Does myeloid expression of TRIB1 regulate plasma lipid levels?. Atherosclerosis, Vol. 241(1) (pp e34-e34)
- 185 Shear Stress Dependent Regulation of p2x4 and p2x7 Receptors in the Endothelium. Heart, Vol. 101(Suppl 4) (pp A104.1-A104)
- 179 Investigation of human monocyte derived macrophage phenotypes for their functional role in atherosclerosis:. Heart, Vol. 101(Suppl 4) (pp A101.2-A102)
- 235 TRIBBLES-1 CONTRIBUTES TO MONOCYTE MIGRATION IN EXPERIMENTAL PERITONITIS. Heart, Vol. 99(suppl 2) (pp A126.1-A126)
- 208 A NOVEL ROLE FOR THE GAS3/PMP22 FAMILY MEMBER EMP2 IN THE REGULATION OF INFLAMMATION. Heart, Vol. 99(suppl 2) (pp A114.2-A115)
- 172 IL-1 BETA SECRETION IN CORONARY VASCULAR ENDOTHELIUM IS MEDIATED BY NEUTROPHIL SERINE PROTEASE AND IS INDEPENDENT OF CASPASE-1.. Heart, Vol. 99(suppl 2) (pp A99.2-A99)
- Neutrophil recruitment in response to intradermal endotoxin challenge in man. LANCET, Vol. 381 (pp 22-22)
- Sarcoplasmic reticulum Ca2+ release, cyclic ADP-ribose and hypoxic pulmonary vasoconstriction in rabbit pulmonary arteries: do O-2-sensing K+ channels play a supporting role?. JOURNAL OF PHYSIOLOGY-LONDON, Vol. 528P (pp 4P-5P)
- Differential distribution of the enzyme activities for the synthesis and metabolism of cyclic ADP-ribose in rabbit pulmonary versus systemic artery smooth muscle: a novel redox sensing pathway?. JOURNAL OF PHYSIOLOGY-LONDON, Vol. 526 (pp 124P-125P)
- Cyclic AMP and cGMP differentially regulate the production of the calcium-mobilising metabolites, nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose. BRITISH JOURNAL OF PHARMACOLOGY, Vol. 124 (pp U19-U19)
- Multiple mechanisms for calcium mobilization in the sea urchin egg. JOURNAL OF PHYSIOLOGY-LONDON, Vol. 499P (pp S5-S6)
- Neutrophil elastase enhances IL-1 beta secretion from coronary endothelium via an endolysosomal mediated mechanism, without caspase-1 activation. ANGIOGENESIS, Vol. 17(4) (pp 941-941). California, USA, 18 October 2014 - 23 October 2014.
Preprints
- Ageing-related defects in macrophage function are driven byMYCandUSF1transcriptional programmes, Cold Spring Harbor Laboratory.
- Myeloid Tribbles 1 induces early atherosclerosis via enhanced foam cell expansion, Cold Spring Harbor Laboratory.
- Research group
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PhD Students
- Mrs Rehab Alqurashi
- Mr Kajus Baidzajevas
- Mr Jack Green
- Miss Laura Martinez-Campesino
- Teaching interests
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- Course Deputy, MRes in Cardiovascular Medicine
- Cardiovascular Pathway Lead, MSc in Molecular Medicine
- CDL401 Vascular Cell Biology module lead
- CDL301 lecturer, Cardiovascular Pharmacology, Biomedical Science BSc
- BMedSci Cluster lead, 2010-2019
- Personal and Academic Tutor to MBChB, BMedSci, MSc & MRes students
- Laboratory Project supervisor to PhD, MSc, MRes, BMedSci, MBChB & MBB four-year MBiolSci students & clinical training fellows
- Teaching activities
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- RCUK Fellow, University of Sheffield, 2005-2010
- Lecturer, University of Sheffield, 2010-2017
- Senior Lecturer, University of Sheffield, 2018-Present
- Professional activities and memberships
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- Departmental REF Lead.
- Member of the British Atherosclerosis Society and British Society of Immunology
- Ethics reviewer
- Member of the Bateson Centre, University of Sheffield (formerly Centre for Developmental and Biomedical Genetics)
- Wellcome Trust PDRA, Laboratory of Profs Alan North & Annmarie Surprenant
- BHF PDRA, Laboratory of Prof. Steven Dower