Dr Peter Cook
Lecturer, Wellcome Trust Sir Henry Dale Fellow
P.C.Cook@exeter.ac.uk
Geoffrey Pope 320
Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK
Overview
Dr Peter Cook is a Wellcome Trust Sir Henry Dale Fellow at the MRC Centre for Medical Mycology. Peter’s research focuses on understanding how the lung-airway environment influences innate immunity to mediate anti-fungal allergic disease, a recognised key neglected area of research. Of the 500,000 asthma-related human deaths occurring annually, 50% are caused by fungal sensitisation to airborne spores of the environmental mould Aspergillus fumigatus. A mechanistic understanding of asthmatic immunopathology will radically improve therapeutic strategies for all asthmatic disease.
Qualifications
PhD. University of York (2004 – 2009).
BSc (Hons) Genetics with a year in industry. University of York (2000 – 2004)
Career
Wellcome Trust Sir Henry Dale Fellow. University of Exeter (2020 – present)
Dean’s Prize Fellow. University of Manchester (2016 – 2020)
Post doctoral researcher. University of Manchester (2013 – 2016)
Post doctoral researcher. University of Edinburgh (2008 – 2013)
Links
Research group links
Research
Research interests
Our lungs are exposed to thousands of fungal spores everyday (particularly Aspergillus), triggering immune cells in the lung to cause asthma and severe allergic disease. Despite the rising number of cases and developing resistance to current therapies, we do not understand how or why Aspergillus causes asthma and this is a recognised key neglected area of research.
Previously my work has identified novel mechanisms on how specialised innate cells, called dendritic cells and macrophages, cause allergic inflammation that underpins asthma. Recently I have discovered that the lung airways govern innate immune cell responses during this inflammation via modifying how they generate energy (metabolic state). Yet how these processes co-ordinate severe asthmatic disease against fungal spores is unknown.
We are now focusing on understanding how the lung-airway environment and the fungal spores themselves, influences the metabolism of dendritic cells and macrophages and their abilty to mediate allergic inflammation. This work will discover how fungal asthma develops, as well as reveal new treatment strategies to prevent and/or treat these conditions in the future.
Links
Publications
Journal articles
Colombo SAP, Brown SL, Hepworth MR, Hankinson J, Granato F, Kitchen SJ, Hussell T, Simpson A, Cook PC, MacDonald AS, et al (2023). Comparative phenotype of circulating versus tissue immune cells in human lung and blood compartments during health and disease. Discovery Immunology, 2(1).
Costain AH, Phythian-Adams AT, Colombo SAP, Marley AK, Owusu C, Cook PC, Brown SL, Webb LM, Lundie RJ, Borger JG, et al (2023). Corrigendum: Dynamics of host immune response development during Schistosoma mansoni infection. Front Immunol, 14 Abstract. Author URL.
Padilla AM, Rosenberg C, Cook P, Sanchez-Valdez F, McElhannon C, Tarleton RL (2023). Delayed Activation of T Cells at the Site of Infection Facilitates the Establishment of Trypanosoma cruzi in Both Naive and Immune Hosts. mSphere, 8(1). Abstract. Author URL.
Hatinguais R, Kay M, Salazar F, Conn DP, Williams DL, Cook PC, Willment JA, Brown GD (2023). Development of Negative Controls for Fc-C-Type Lectin Receptor Probes. Microbiol Spectr, 11(3). Abstract. Author URL.
Cook PC, Drummond RA (2023). Fungal pathogens: the underappreciated parasites that are now in the spotlight. Parasite Immunology, 45(2).
Earle K, Valero C, Conn DP, Vere G, Cook PC, Bromley MJ, Bowyer P, Gago S (2023). Pathogenicity and virulence of Aspergillus fumigatus. Virulence, 14(1). Abstract. Author URL.
Houlder EL, Costain AH, Nambuya I, Brown SL, Koopman JPR, Langenberg MCC, Janse JJ, Hoogerwerf MA, Ridley AJL, Forde-Thomas JE, et al (2023). Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis. Nature Communications, 14(1). Abstract.
Costain AH, Phythian-Adams AT, Colombo SAP, Marley AK, Owusu C, Cook PC, Brown SL, Webb LM, Lundie RJ, Smits HH, et al (2022). Dynamics of Host Immune Response Development During <i>Schistosoma mansoni</i> Infection. FRONTIERS IN IMMUNOLOGY, 13 Author URL.
Furlong-Silva J, Cook PC (2022). Fungal-mediated lung allergic airway disease: the critical role of macrophages and dendritic cells. PLoS Pathogens, 18(7). Abstract.
Salazar F, Bignell E, Brown GD, Cook PC, Warris A (2022). Pathogenesis of Respiratory Viral and Fungal Coinfections. Clin Microbiol Rev, 35(1). Abstract. Author URL.
Hepworth MR, Greenhalgh AD, Cook PC (2021). B cells on the brain: meningeal IgA and a novel gut-brain firewall. Immunol Cell Biol, 99(1), 17-20. Abstract. Author URL.
Webb LM, Phythian-Adams AT, Costain AH, Brown SL, Lundie RJ, Forde-Thomas J, Cook PC, Jackson-Jones LH, Marley AK, Smits HH, et al (2021). Plasmacytoid Dendritic Cells Facilitate Th Cell Cytokine Responses throughout <i>Schistosoma mansoni</i> Infection. ImmunoHorizons, 5(8), 721-732. Abstract.
Houlder EL, Costain AH, Cook PC, MacDonald AS (2021). Schistosomes in the Lung: Immunobiology and Opportunity. Frontiers in Immunology, 12 Abstract.
Jones G-R, Brown SL, Phythian-Adams AT, Ivens AC, Cook PC, MacDonald AS (2020). The Methyl-CpG-Binding Protein Mbd2 Regulates Susceptibility to Experimental Colitis via Control of CD11c+ Cells and Colonic Epithelium. Front Immunol, 11 Abstract. Author URL.
Furukawa T, van Rhijn N, Fraczek M, Gsaller F, Davies E, Carr P, Gago S, Fortune-Grant R, Rahman S, Gilsenan JM, et al (2020). The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus. Nat Commun, 11(1). Abstract. Author URL.
Yu K, Youshani AS, Wilkinson FL, O'Leary C, Cook P, Laaniste L, Liao A, Mosses D, Waugh C, Shorrock H, et al (2019). A nonmyeloablative chimeric mouse model accurately defines microglia and macrophage contribution in glioma. Neuropathol Appl Neurobiol, 45(2), 119-140. Abstract. Author URL.
Rückerl D, Cook PC (2019). Macrophages assemble! But do they need IL-4R during schistosomiasis?. European Journal of Immunology, 49(7), 996-1000. Abstract.
Svedberg FR, Brown SL, Krauss MZ, Campbell L, Sharpe C, Clausen M, Howell GJ, Clark H, Madsen J, Evans CM, et al (2019). The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation. Nature Immunology, 20(5), 571-580. Abstract.
Bancroft AJ, Levy CW, Jowitt TA, Hayes KS, Thompson S, Mckenzie EA, Ball MD, Dubaissi E, France AP, Bellina B, et al (2019). The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function. Nature Communications, 10(1). Abstract.
Jones G-R, Bain CC, Fenton TM, Kelly A, Brown SL, Ivens AC, Travis MA, Cook PC, MacDonald AS (2018). Dynamics of Colon Monocyte and Macrophage Activation During Colitis. Front Immunol, 9 Abstract. Author URL.
May S, Owen H, Phesse TJ, Greenow KR, Jones GR, Blackwood A, Cook PC, Towers C, Gallimore AM, Williams GT, et al (2018). Mbd2 enables tumourigenesis within the intestine while preventing tumour-promoting inflammation. Journal of Pathology, 245(3), 270-282. Abstract.
Grabiec AM, Denny N, Doherty JA, Happonen KE, Hankinson J, Connolly E, Fife ME, Fujimori T, Fujino N, Goenka A, et al (2017). Diminished airway macrophage expression of the Axl receptor tyrosine kinase is associated with defective efferocytosis in asthma. Journal of Allergy and Clinical Immunology, 140(4), 1144-1146.e4.
Youshani AS, Yu K, Wilkinson F, O’Leary C, Cook P, Liao A, Pathmanaban O, Waugh C, Shorrock H, MacDonald A, et al (2017). IMMU-50. A NOVEL CHIMERIC MODEL TO ACCURATELY IDENTIFY TAMMs IN GLIOBLASTOMA. Neuro-Oncology, 19(suppl_6), vi123-vi124.
Webb LM, Lundie RJ, Borger JG, Brown SL, Connor LM, Cartwright ANR, Dougall AM, Wilbers RHP, Cook PC, Jackson-Jones LH, et al (2017). Type I interferon is required for T helper (Th) 2 induction by dendritic cells. EMBO Journal, 36(16), 2404-2418. Abstract.
Lundie RJ, Webb LM, Marley AK, Phythian-Adams AT, Cook PC, Jackson-Jones LH, Brown S, Maizels RM, Boon L, O'Keeffe M, et al (2016). A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection. Immunology and Cell Biology, 94(4), 400-410. Abstract.
Cook PC, MacDonald AS (2016). Dendritic cells in lung immunopathology. Seminars in Immunopathology, 38(4), 449-460. Abstract.
Cook PC, Owen H, Deaton AM, Borger JG, Brown SL, Clouaire T, Jones GR, Jones LH, Lundie RJ, Marley AK, et al (2015). A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nature Communications, 6 Abstract.
Prendergast CT, Sanin DE, Cook PC, Mountford AP (2015). CD4<sup>+</sup> T cell hyporesponsiveness after repeated exposure to Schistosoma mansoni larvae is dependent upon interleukin-10. Infection and Immunity, 83(4), 1418-1430. Abstract.
Zhang X, Cook PC, Zindy E, Williams CJ, Jowitt TA, Streuli CH, MacDonald AS, Redondo-Muñoz J (2015). Integrin α4β1 controls G9a activity that regulates epigenetic changes and nuclear properties required for lymphocyte migration. Nucleic Acids Research, 44(7), 3031-3044. Abstract.
Jones LH, Cook PC, Ivens AC, Thomas GD, Phythian-Adams AT, Allen JE, MacDonald AS (2015). Modulation of dendritic cell alternative activation and function by the vitamin a metabolite retinoic acid. International Immunology, 27(11), 589-596. Abstract.
Fujimori T, Grabiec AM, Kaur M, Bell TJ, Fujino N, Cook PC, Svedberg FR, Macdonald AS, Maciewicz RA, Singh D, et al (2015). The Axl receptor tyrosine kinase is a discriminator of macrophage function in the inflamed lung. Mucosal Immunology, 8(5), 1021-1030. Abstract.
Deaton AM, Cook PC, De Sousa D, Phythian-Adams AT, Bird A, Macdonald AS (2014). A unique DNA methylation signature defines a population of IFN-γ/IL-4 double-positive T cells during helminth infection. European Journal of Immunology, 44(6), 1835-1841. Abstract.
Morrison VL, James MJ, Grzes K, Cook P, Glass DG, Savinko T, Lek HS, Gawden-Bone C, Watts C, Millington OR, et al (2014). Loss of beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype. Nat Commun, 5 Abstract. Author URL.
Jones G-R, Cook P, Webb L, MacDonald A (2013). OC-089 Epigenetic Control of GI Inflammation Via the Methyl-Binding Protein MBD2. Gut, 62(Suppl 1).
Cook PC, Jones LH, Jenkins SJ, Wynn TA, Allen JE, MacDonald AS (2012). Alternatively activated dendritic cells regulate CD4 <sup>+</sup> T-cell polarization in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America, 109(25), 9977-9982. Abstract.
Ferret-Bernard S, Castro-Borges W, Dowle AA, Sanin DE, Cook PC, Turner JD, MacDonald AS, Thomas JR, Mountford AP (2012). Plasma membrane proteomes of differentially matured dendritic cells identified by LC-MS/MS combined with iTRAQ labelling. Journal of Proteomics, 75(3), 938-948. Abstract.
Turner JD, Jenkins GR, Hogg KG, Aynsley SA, Paveley RA, Cook PC, Coles MC, Mountford AP (2011). CD4<sup>+</sup>CD25<sup>+</sup> regulatory cells contribute to the regulation of colonic Th2 granulomatous pathology caused by schistosome infection. PLoS Neglected Tropical Diseases, 5(8). Abstract.
Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD, Van Rooijen N, MacDonald AS, Allen JE (2011). Local macrophage proliferation, rather than recruitment from the blood, is a signature of T <inf>H</inf>2 inflammation. Science, 332(6035), 1284-1288. Abstract.
Cook PC, Aynsley SA, Turner JD, Jenkins GR, van Rooijen N, Leeto M, Brombacher F, Mountford AP (2011). Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells. PLoS Pathogens, 7(3). Abstract.
Paveley RA, Aynsley SA, Turner JD, Bourke CD, Jenkins SJ, Cook PC, Martinez-Pomares L, Mountford AP (2011). The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNγ production. International Journal for Parasitology, 41(13-14), 1335-1345. Abstract.
Phythian-Adams AT, Cook PC, Lundie RJ, Jones LH, Smith KA, Barr TA, Hochweller K, Anderton SM, Hämmerling GJ, Maizels RM, et al (2010). CD11c depletion severely disrupts Th2 induction and development in vivo. Journal of Experimental Medicine, 207(10), 2089-2096. Abstract.
Paveley RA, Aynsley SA, Cook PC, Turner JD, Mountford AP (2009). Fluorescent imaging of antigen released by a skin-invading helminth reveals differential uptake and activation profiles by antigen presenting cells. PLoS Neglected Tropical Diseases, 3(10). Abstract.
Fay MF, Bone R, Cook P, Kahandawala I, Greensmith J, Harris S, Pedersen HAE, Ingrouille MJ, Lexer C (2009). Genetic diversity in Cypripedium calceolus (Orchidaceae) with a focus on north-western Europe, as revealed by plastid DNA length polymorphisms. Ann Bot, 104(3), 517-525. Abstract. Author URL.
Conferences
Youshani AS, Yu K, Wilkinson F, O'leary C, Cook P, Liao A, Pathmanaban O, Waugh C, Shorrock H, Macdonald A, et al (2018). IDENTIFYING TUMOUR ASSOCIATED MACROPHAGES AND MICROGLIA IN AN EXPERIMENTAL GLIOBLASTOMA MODEL. Author URL.
Webb LM, Lundie RJ, Borger JG, Cartwright AN, Cook PC, Brown SL, Jackson-Jones L, Phythian-Adams AT, Davis DM, MacDonald AS, et al (2016). A central role for Type I IFN in the induction of Th2 responses by dendritic cells. Author URL.
Jones G-R, MacDonald A, Cook P (2016). Epigenetic control of colonic epithelial antigen processing, barrier function, and the microbiome via methyl-CpG binding domain protein 2. Author URL.
Jones G-R, Cook P, MacDonald A (2016). Epigenetic control of colonic epithelial antigen processing, barrier function, and the microbiome via methyl-CpG binding domain protein 2. Author URL.
Jones G-R, Cook P, MacDonald A, Fenton T, Kelly A, Travis M, Campbell S (2016). Inflammatory monocytes are key regulators of colonic inflammation in murine and human IBD. Author URL.
Redondo-Munoz J, Zhang X, Whang P, Cook P, Zindy E, Williams CJ, Jowitt TA, MacDonald AS (2016). ROLE OF G9A AND EPIGENETIC CHANGES IN LEUKEMIA CELL MIGRATION AND THEIR REGULATION BY VLA4 INTEGRIN. Author URL.
Crooks J, Brown S, Forss C, Phythian-Adams A, Cook P, Brunet LR, MacDonald A (2016). The impact of <i>Mycobacterium obuense</i> on innate and adaptive immunity. Author URL.
Jones G-R, Cook P, MacDonald A (2014). Epigenetic control of colonic inflammation via the methyl-binding protein Mbd2. Author URL.
Prendergast C, Cook P, Mountford A (2012). Mechanisms of the lymphocyte hypo-responsiveness observed after multiple infections of the skin with <i>Schistosoma mansoni</i> cercariae. Author URL.
Prendergast C, Cook P, Mountford A (2011). Mechanisms of the lymphocyte hypo-responsiveness observed after multiple infections of the skin with <i>S</i>. <i>mansoni</i> cercariae. Author URL.
Cook PC, Jones LH, Phythian-Adams AT, Lundie RJ, Allen JE, MacDonald AS (2009). IL-4 triggers alternative activation of dendritic cells. Author URL.
Supervision / Group
Research Fellows
- Masahiro Abe - Visiting research fellow
- Matthew Steward - MRC CMM Clinical Fellow
Postdoctoral researchers
- Julio Silva - Post doctoral research fellow
Postgraduate researchers
- Daniel Conn - MRC CMM PhD studentship
- Phuong Tuyen Nguyen - MRC CMM PhD studentship
- Emily Plumpton - NIHR Exeter BRC PhD studentship
- George Vere - E3 England PhD studentship
