Dr Helen Marriott
PhD
Clinical Medicine, School of Medicine and Population Health
Lecturer in Respiratory Infection
+44 114 215 9537
Full contact details
Clinical Medicine, School of Medicine and Population Health
The Medical School
Beech Hill Road
91Ö±²¥
S10 2RX
- Profile
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For enquiries please contact - ClinMed-Operational@sheffield.ac.uk
I joined the University of 91Ö±²¥ in 1995 from the Department of Respiratory Physiology, Papworth Hospital, Cambridge. From 1995 to 2001 my research was on the pulmonary circulation, focusing on animal models of pulmonary hypertension. This formed the basis of my PhD, "Pulmonary hypertension: susceptibility and treatment in rat models".
In 2001 I joined Professor David Dockrell´s group as a post-doctoral research associate investigating the role of macrophage apoptosis in pneumococcal infection.
In 2005 I was awarded an independent fellowship from the British Lung Foundation to investigate the effects of influenza A virus on macrophage innate immune function.
In 2015 I was appointed Lecturer in Respiratory Infection.
Since 2016 I have been the academic lead of the Medical School Flow Cytometry Core Facility.
- Research interests
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My main research interest is in the role of macrophages in host defense against respiratory pathogens, in particular Streptococcus pneumoniae. I am also interested in the effect of influenza A virus on macrophage function, its effect on the regulation of macrophage apoptosis and how this may lead to increased susceptibility to bacterial superinfections. I have been using a variety of in vitro, in vivo models and computational models to support this research.
Current projects
Re-engaging antimicrobial killing by macrophages to combat antimicrobial resistance.
I was awarded an Innovation grant from the MRC as part of the cross research council initiative Tackling Antimicrobial Resistance to identify new targets for novel antibacterials. We have described macrophage apoptosis associated killing as an alternative means by which macrophages kill bacteria, however we have found that this is subverted in some patients at increased risk of bacterial infections, such as Chronic Obstructive Lung Disease. In addition some bacteria, notably S. aureus, can prevent macrophage apoptosis associated killing to survive within macrophages. In this grant we will screen and develop compounds to engage macrophage apoptosis as a means to improve bacterial killing and modify inflammation. By targeting the host, rather than the pathogen, we anticipate this will avoid antimicrobial resistance. This concept is a focus of the MRC Collaborative Grant, Optimising Innate Host Defence to Combat Antimicrobial Resistance of which I am a co-investigator.
Molecular analysis of the effects of influenza A virus on macrophage innate immune function (Wellcome Trust VIP award and Personal fellowship from the British Lung Foundation).
The aim of my fellowship was to characterise the effect of influenza A virus on macrophage function, with particular emphasis on its effect on the regulation of macrophage apoptosis. I have established in vitro macrophage and in vivo murine models of IAV infection and shown that both human monocyte derived macrophages and murine macrophages undergo apoptosis after influenza A virus infection. I am investigating how this relates to cytokine production, generation of antimicrobial molecules and killing of bacteria.
Role of ubiquitination in regulation of macrophage viability after bacterial infection.
Macrophages do not undergo apoptosis after infection with S. aureus or N. meningitidis, and I have shown this is associated with an increase in the anti-apoptotic protein Mcl-1. I am currently investigating the mechanism behind this up-regulation focusing on the role of post-translational modifications, in particular ubiquitination, and identifying the bacterial factors responsible.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- . Frontiers in Cellular and Infection Microbiology, 10.
- . Journal of Theoretical Biology, 497.
- . American Journal of Respiratory and Critical Care Medicine.
- . American Journal of Respiratory and Critical Care Medicine, 197(12).
- . American Journal of Respiratory and Critical Care Medicine, 196(7), 845-855.
- . Science Immunology, 2(8).
- . Cellular Microbiology, 18(1), 80-96.
- . mBio, 5(5).
- . Blood, 123(3), 366-376.
- . Thorax, 67(11), 985-992.
- . PLoS Pathogens, 8(7), 30.
- . Thorax, 67(9), 796-803.
- . Infect Immun, 80(3), 1140-1149.
- . J Leukoc Biol, 90(5), 855-865.
- . Mol Cell Proteomics, 10(6), M111.008193.
- . J Clin Invest, 121(3), 1053-1063.
- . PLoS Pathog, 7(1), e1001262.
- . J Immunol, 185(5), 2968-2979.
- . PLoS One, 5(1), e8668.
- . Am J Respir Crit Care Med, 177(8), 887-895.
- . J Immunol, 177(9), 6480-6488.
- . Infect Immun, 74(1), 729-733.
- . J CLIN INVEST, 115(2), 359-368.
- . FASEB J, 18(10), 1126-1128.
- . J Immunol, 171(10), 5380-5388.
All publications
Journal articles
- . Frontiers in Cellular and Infection Microbiology, 10.
- . Journal of Theoretical Biology, 497.
- . ACS Nano.
- . Frontiers in Immunology, 10.
- . American Journal of Respiratory and Critical Care Medicine.
- . Frontiers in Medicine, 5.
- . American Journal of Respiratory and Critical Care Medicine, 197(12).
- . American Journal of Respiratory and Critical Care Medicine, 196(7), 845-855.
- . Journal of Clinical Investigation, 127(9), 3407-3420.
- . Science Immunology, 2(8).
- . European Journal of Pharmacology, 793, 49-55.
- . British Journal of Pharmacology, 173(21), 3099-3109.
- . Cellular Microbiology, 18(1), 80-96.
- . mBio, 5(5).
- . Clin Exp Immunol, 174(2), 193-202.
- . Blood, 123(3), 366-376.
- . J Infect, 66(1), 1-17.
- . Cell Tissue Res, 350(3), 455-464.
- . Thorax, 67(11), 985-992.
- . PLoS Pathogens, 8(7), 30.
- . Thorax, 67(9), 796-803.
- . Infect Immun, 80(3), 1140-1149.
- . J Leukoc Biol, 90(5), 855-865.
- . Mol Cell Proteomics, 10(6), M111.008193.
- . J Clin Invest, 121(3), 1053-1063.
- . C13. PATHOGENESIS OF ACUTE LUNG INJURY.
- . PLoS Pathog, 7(1), e1001262.
- . J Immunol, 185(5), 2968-2979.
- . PLoS One, 5(1), e8668.
- . Curr Mol Med, 8(6), 497-509.
- . Am J Respir Crit Care Med, 177(8), 887-895.
- . J Immunol, 180(5), 3502-3511.
- . Am J Respir Crit Care Med, 177(1), 35-43.
- . J Immunol, 179(12), 8544-8553.
- . Exp Lung Res, 33(10), 493-505.
- . Vaccine, 25(13), 2485-2490.
- . J Immunol, 177(9), 6480-6488.
- . Int J Biochem Cell Biol, 38(11), 1848-1854.
- . Infect Immun, 74(1), 729-733.
- . J CLIN INVEST, 115(2), 359-368.
- . Journal of Clinical Investigation, 115(2), 359-368.
- . FASEB J, 18(10), 1126-1128.
- . J Immunol, 171(10), 5380-5388.
- . Clinical Science, 103(1), 107-107.
- . Clinical Science, 103(1), 107-107.
- Is circulating nitrite a directly acting vasodilator?: authors' reply. CLIN SCI, 103(1), 108-110.
- . Clinical Science, 102(1), 77-83.
- Circulating nitrite anions are a directly acting vasodilator and are donors for nitric oxide.. Clin Sci (Lond), 102(1), 77-83.
- . Chest, 116(4), 921-930.
- . Seminars in Respiratory and Critical Care Medicine, 19(01), 91-95.
- The role of nitric oxide in respiratory disease. Schweizerische Medizinische Wochenschrift, 127(17), 709-714.
- . Frontiers in Cellular and Infection Microbiology, 13.
- . Frontiers in Immunology, 13.
- . eLife, 4.
- . PLoS ONE, 3(6), e2368-e2368.
- .
Chapters
- , Mucosal Immunology of Acute Bacterial Pneumonia (pp. 1-48). Springer New York
- , Nitric Oxide in Pulmonary Processes: Role in Physiology and Pathophysiology of Lung Disease (pp. 201-208). Birkhäuser Basel
Conference proceedings papers
- . The influence of influenza: from cells to humans
- . BTS/BALR/BLF Early Career Investigators awards symposium
- Vascular Smooth Muscle Derived TRAIL is Required for Development of Pulmonary Arterial Hypertension in Sugen 5416 / Hypoxia Mice. CIRCULATION, Vol. 138
- . Thorax, Vol. 71(Suppl 3) (pp A61.2-A62)
- The Role Of Pellino-1 In Modulating Signalling Pathways Controlling The Inflammatory Response To Viral Stimuli In Airway Epithelial Cells. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol. 193
- Prostaglandin E2 Activates Ep4 Receptors To Inhibit Pro-Inflammatory Cytokine Release From Human Lung Macrophages. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol. 189
- . THORAX, Vol. 68 (pp A139-A139)
- . THORAX, Vol. 68 (pp A140-A140)
- . THORAX, Vol. 67 (pp A1-A1)
- . B28. EMERGING BIOMARKERS OF COMPLEX LUNG DISEASES
- . C31. REGULATION OF LUNG INFLAMMATION
- . Thorax, Vol. 66(Suppl 4) (pp A51-A52)
- . D14. INSIGHTS INTO PATHOGENESIS OF LUNG FIBROSIS AND GRANULOMAS
- . A35. LESSONS IN LUNG INFECTIONS
- MONOCYTE DEATH PROCESSES ARE SUBVERTED BY MENINGOCOCCI. J INFECTION, Vol. 61(6) (pp 517-518)
- Monocytes promote T-lymphocyte apoptosis following Streptococcus pneumoniae challenge. IMMUNOLOGY, Vol. 131 (pp 179-179)
- Regulation Of Apoptosis In A549 Cells After Influenza A Virus Infection. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol. 181
- Macrophage Apoptosis after Influenza A Virus Infection.. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol. 179
- The role of TNF-related apoptosis inducing ligand in acute lung injury. THORAX, Vol. 62 (pp A62-A62)
- Maintenance of macrophage viability after meningococcal infection. IMMUNOLOGY, Vol. 120 (pp 82-82)
- Apoptotic macrophages limit inflammation in pneumococcal pneumonia. JOURNAL OF LEUKOCYTE BIOLOGY (pp 77-77)
- Quantification of pulmonary haemodynamic and vascular changes in chronic hypoxia and recovery in rats. JOURNAL OF PHYSIOLOGY-LONDON, Vol. 544 (pp 116P-116P)
- Reversal of pulmonary hypertension and vascular remodelling by an endothelin receptor antagonist in the chronic hypoxic rat model. THORAX, Vol. 56 (pp 75-76)
- Fawn-hooded rats and pulmonary hypertension: histological and haemodynamic comparison with Wistar rats. J PHYSIOL-LONDON, Vol. 533 (pp 80P-81P)
- Pulmonary vasodilation by airway delivered prostacyclin analogues, UT-15 & pegylated UT-15. THORAX, Vol. 55 (pp A35-A35)
- Chronic dexfenfluramine treatment reduces the levels of serotonin transporter mRNA in normoxic and chronically hypoxic Wistar and Fawn hooded rats.. THORAX, Vol. 54 (pp A40-A40)
- Pulmonary vasoactivity of fenfluramines and selective serotonin reuptake inhibitors, fluoxetine and amitriptyline, in the rat. THORAX, Vol. 54 (pp A40-A40)
- Inhalation of endothelin(A/B) receptor antagonist partially reverses chronic hypoxic pulmonary hypertension in the rat. THORAX, Vol. 54 (pp A40-A40)
- Anti-ET-1 oligonucleotides as a potential treatment for pulmonary hypertension.. THORAX, Vol. 54 (pp A39-A39)
- Transfer of phosphorothioate oligodeoxynucleotides from the airway to the perfusate in isolated perfused rat lungs. AM J RESP CRIT CARE, Vol. 159(3) (pp A168-A168)
- Chronic dexfenfluramine treatment reduces the levels of serotonin transporter mRNA in normoxic and chronically hypoxic wistar and fawn hooded rats.. AM J RESP CRIT CARE, Vol. 159(3) (pp A168-A168)
- Attenuated pulmonary and systemic vasodilator response to serotonin in the Fawn Hooded rat. AM J RESP CRIT CARE, Vol. 159(3) (pp A165-A165)
- Pulmonary and systemic action of 5-HT in the Fawn Hooded rat: a model of inherited pulmonary and systemic hypertension. J PHYSIOL-LONDON, Vol. 511P (pp 108P-109P)
- Rapid increases in the levels of preproendothelin-1 mRNA in the isolated perfused rat lung exposed to acute hypoxia. Thorax, Vol. 53(SUPPL. 4)
- Altered vascular reactivity to serotonin in the fawn hooded rat; a model of spontaneous pulmonary and systemic hypertension. Thorax, Vol. 53(SUPPL. 4)
- The effect of dexfenfluramine on 5-hydroxytryptamine clearance in the porcine lung. Thorax, Vol. 52(SUPPL. 6)
- Enhanced pulmonary vasoreactivity to serotonin in the Fawn hooded rat. Thorax, Vol. 52(SUPPL. 6)
Preprints
- Teaching activities
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I contribute to several modules in the MSc in Molecular Medicine. I am the module leader for the following modules:
- Modulating Immunity
- Molecular and Cellular Basis of Disease
- Pathogenicity of Viruses and Fungi
I am also the lead for the Experimental Medicine pathway.
I contribute to the teaching and supervision of students in the Medical School MBChB and Molecular Biology and Biotechnology BSc and MBiolSci courses.
I also teach the Postgraduate Induction course of the Faculty of Health and am the unfair means officer for the Medical School (PGR).
- Professional activities and memberships
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- Member of University of 91Ö±²¥ Animal Welfare and Ethical Review Board / 3Rs Committee