个人简介
2013-present Associate Professor of Fungal Immunology, School of Biosciences, University of Exeter
2007-2013 Senior Lecturer in Immunology, School of Biosciences, University of Exeter
2003-2007 Lecturer in Immunology, School of Biosciences, University of Exeter
2001-2003 Postdoctoral Research Associate in School of Biosciences, University of Exeter
1998-2001 University Research Fellow, School of Biosciences, University of Exeter
1997-1998 Temporary lecturer in Molecular Genetics, School of Biosciences, University of Exeter
1994-1997 Postdoctoral Research Associate in Plant Sciences Department, University of Cambridge
1991-1994 Postdoctoral Research Associate in Plant Sciences Department, University of Oxford
研究领域
Tracking human pathogenic fungi by using monoclonal antibodies
The frequency of invasive mycoses by opportunistic fungal pathogens has increased dramatically over the past two decades. This increase is directly related to increasing patient populations at risk for the development of infections, which include the elderly, premature babies, solid-organ and bone marrow transplant recipients, individuals with AIDS, neoplastic disease and those receiving immunosuppressive therapies or cytotoxic drugs. In addition to well-known opportunistic pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, other species of yeast-like fungi and filamentous fungi have emerged as serious pathogens of humans over recent years. Many of these organisms such as the zygomycete Rhizopus oryzae and members of the ascomycete phylum, for example Scedosporium prolificans, Pseudallescheria boydii, Fusarium solani, and Trichoderma longibrachiatum, are ubiquitous soil-borne organisms. The saprotrophic lifestyles of these fungi and potentially infectious Aspergillus spp., enable them to utilize a wide range or substrates including decaying plant material thereby facilitating efficient colonization of their natural habitats, soils and composts. As soil saprotrophs they play an important role in the recycling of organic matter in terrestrial ecosystems and while some species such as F. solani are plant pathogens also, others such as Trichoderma species display mycoparasitic and plant-growth-promotional activities that have been exploited in the biological control of plant disease and in the enhancement of crop productivity. Despite these positive attributes, soil-borne fungi can have significant negative impacts on human health, causing frequently fatal disseminated infections in the immunocompromised host, with disproportionately high rates of mortality and morbidity.
Aspergillus fumigatus, Fusarium solani and Scedosporium spp. are agents of ‘hyalohyphomycosis’, a term used to describe infections caused by hyaline, septate, fungi in infected tissues. Aspergillus fumigatus, second only to Candida spp. as the cause of nosocomial (hospital-acquired) invasive fungal infections, is first and foremost a pulmonary pathogen causing aspergillomas (fungus balls) that occlude the lung cavities. However, the fungus can also invade the host via lung tissue resulting in a disease known as invasive aspergillosis. This disease is now a major direct or contributory cause of death in haematological malignancy, bone marrow and solid organ transplant patients. Fusarium spp., have long been associated with infections of the skin, nail and cornea, but are now becoming increasingly recognized as a cause of invasive fungal infection (fusariosis) in neutropenic patients and in those undergoing transplantation. Indeed, some hospitals have reported Fusarium to be second only to Aspergillus as the cause of life-threatening filamentous fungal infections in their transplant patients. Scedosporium apiospermum is a well known causative agent of mycetoma (tumour-like swellings with draining sinuses), but this species and the related species Scedosporium prolificans have also recently emerged as significant invasive pathogens, particularly of immunocompromised patients, and now account for ~25% of non-Aspergillus infections in high risk patient groups. Rhizopus oryzae, an aseptate fungus, is the most important agent of mucormycosis in patients that have serious underlying conditions such as diabetes mellitus, starvation, burns, or other major trauma.
Opportunistic mycoses represent formidable diagnostic challenges. It is imperative that diagnosis is made without delay, since prognosis worsens significantly in the absence of recognition and timely intervention with antifungal agents. Identification of fungi in histological sections is problematic because of a common appearance (colourless, septate, hyphae with a wide range of branching angles). Definitive identification in hyalohyphomycosis therefore requires isolation of fungi in culture and identification using morphological characteristics such as spore-bearing structures. This takes considerable time and requires taxonomic expertise. Consequently, rapid diagnostic tests that accurately discriminate between the different pathogens are urgently needed. A characteristic of fungi such as A. fumigatus and F. solani, R. oryzae and Candida spp., in particular, is angioinvasion and dissemination via the blood. This property presents an opportunity to track the fungi immunologically using techniques that detect characteristic signatures created by their circulating antigens.
One such technique is hybridoma technology. It allows the production of monoclonal antibodies (mAbs) that are specific to individual genera, species or even isolates of fungi and are capable of discriminating between active growth and quiescent spore production. I have successfully used monoclonal antibodies to detect fungi in soil and composts and in plant material and have developed highly specific and sensitive immunological assays for the quantification of interacting population of fungi in mixed species soil-based systems. I have also used mAbs to develop user-friendly, diagnostic tests (lateral flow devices) for the rapid detection of plant pathogens and beneficial fungi in soils and in plant materials. One such device has been developed for tracking biocontrol strains of Trichoderma in the plant rhizosphere.
An LFD specific to Aspergillus spp. has already been developed for the rapid serodiagnosis of invasive aspergillosis. The LFD incorporates a mAb that binds to a protein epitope on an extracellular antigen secreted constitutively during invasive growth of the pathogen. Circulating antigen can be detected in serum or bronchoalveolar lavage (BAL) samples from patients at risk from IA, avoiding the need for invasive biopsy sampling. Similar devices will be developed for the rapid serodiagnosis of pseudallescheriasis, fusariosis and mucormycosis using specific mAbs I have recently developed to these fungi.
In 2012, I established a University of Exeter spin-out company Isca Diagnostics Ltd. (www.iscadiagnostics.co.uk) to allow commercial exploitation of my university research in medical mycology and immunodiagnostics. With financial support from the Open Innovation Fund, legal guidance from the University’s RKT department (Neil Hayes and Rachael Baird) and the business support of Rob Misselbrook (UEC Enterprises Ltd.), ISCA Diagnostics Ltd. was incorporated as a private limited company (company number 8010751) on 29th March 2012. The company’s IP currently encompasses the Aspergillus-specific monoclonal antibody JF5 that he generated and used to develop a point-of-care test (lateral-flow device) for the rapid (10 min) diagnosis of invasive pulmonary diagnosis using human serum and bronchoalveolar lavage fluids. The company secured angel funding of £85k to allow manufacturing of the LFD according to FDA approved manufacturing guidelines and to allow HMRA CE-marking of the test for use in Europe as a general medical IVD in early 2013. The CE-marked device will also be evaluated by the NIH-fundedAspergillus Technology (AsTec) Consortium (www.astecdiagnostics.org) in September 2013, which will provide the necessary documentation of external LFD validation for a US FDA 510(k) application. The company has recently signed a distribution agreement with OLM Medical for global distribution of the device and a royalty agreement on sales of the LFD. Supporting documentation (ISCA Incorporation Certificate, Company Business Plan, Shareholders Agreement, Distribution Agreement and IP Agreement) is available from Dr Thornton or RKT upon request.
Because of my success in bench-to-bedside medical diagnostics research and commercialisation, he has been selected to compose one of the six Biosciences Impact Case Studies for REF2014. His Case Study entitled ‘Commercial Exploitation of a Novel Diagnostic Test for Invasive Pulmonary Aspergillosis’ describes the underpinning research and impact of my work in dramatically improving the speed and accuracy of diagnosis of a frequently fatal pulmonary infection of haematological malignancy and transplant patients.
My work on the commercial exploitation of the Aspergillus LFD has been submitted by the University for the 2013 PraxisUnico Impact Awards in the ‘Aspiring’ Category and was shortlisted for the University Impact Awards in 2013.
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Dillon MJ, Bowkett AE, Bungard MJ, Beckman K, O'Brien M, Bates K, Fisher MC, Stevens JR, Thornton CR (In Press). Tracking the amphibian pathogens Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans by using a highly specific monoclonal antibody and lateral-flow technology. Microbial Biotechnology Full text.
Escudero N, Ferreira SR, Lopez-Moya F, Naranjo-Ortiz MA, Marin-Ortiz AI, Thornton CR, Lopez-Llorca LV (2016). Chitosan enhances parasitism of Meloidogyne javanica eggs by the nematophagous fungus Pochonia chlamydosporia. Fungal Biology, 120(4), 572-585. Abstract. Article has an altmetric score of 4
Al-Maqtoofi M, Thornton CR (2016). Detection of human pathogenic Fusarium species in hospital and communal sink biofilms by using a highly specific monoclonal antibody. Environmental Microbiology Abstract. Full text. Article has an altmetric score of 1
Sharpe RA, Le Cocq K, Nikolaou V, Osborne NJ, Thornton CR (2016). Identifying risk factors for exposure to culturable allergenic fungi in energy efficient homes by using highly specific monoclonal antibodies. Environmental Research, 144, 32-42. Abstract. Full text. Article has an altmetric score of 3
Rolle A-M, Hasenberg M, Thornton CR, Solouk-Saran D, Männ L, Weski J, Maurer A, Fischer E, Spycher P, Schibli R, et al (2016). Immuno-PET/MR imaging allows specific detection of. Aspergillus fumigatus lung infection in vivo. Proceedings of the National Academy of Sciences of USA, 113(8), 1026-1033. Abstract. Full text. Article has an altmetric score of 49
Wiehr S, Warnke P, Rolle A-M, Schutz M, Kohlhofer U, Quintanilla-Martinez de Fend L, Maurer A, Thornton C, Boschetti F, Reischl G, et al (2016). New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection. Oncotarget, 7, 10990-11001. Abstract. Full text.
Al-Laaeiby A, Kershaw M, Penn T, Thornton CR (2016). Targeted disruption of melanin biosynthesis genes in the human pathogenic fungus Lomentospora prolificans and its consequences for pathogen survival. International Journal of Molecular Sciences, 17(4), 1-18. Abstract. Full text. Article has an altmetric score of 1
Shaw S, Le Cocq K, Paszkiewicz K, Moore K, Winsbury R, Studholme D, Salmon D, Thornton CR, Grant MR (2016). Transcriptional reprogramming underpins enhanced plant growth promotion by the biocontrol fungus Trichoderma hamatum GD12 during antagonistic interactions with Sclerotinia sclerotiorum in soil. Molecular Plant Pathology Abstract. Full text. Article has an altmetric score of 16
Prattes J, Lackner M, Eigl S, Reischies F, Raggam RB, Koidl C, Flick H, Wolfler A, Neumeister P, Thornton CR, et al (2015). Diagnostic accuracy of the Aspergillus specific Bronchoalveolar Lavage Lateral-Flow Assay in Haematological Malignancy Patients. Mycoses: diagnosis, therapy and prophylaxis of fungal diseases, 58(8), 461-469. Article has an altmetric score of 3
Sharpe R, Thornton CR, Nikolaou V, Osborne N (2015). Fuel poverty increases risk of mould contamination, regardless of adult risk perception & ventilation in social housing properties. Environment International, 79, 115-129. Article has an altmetric score of 8
Eigl S, Prattes J, Reischies FM, Raggam RB, Spiess B, Reinwald M, Buchheidt D, Thornton CR, Krause R, Flick H, et al (2015). Galactomannan Testing and Aspergillus PCR in same-day bronchoalveolar lavage and blood samples obtained from patients with hematological malignancies at risk for invasive mould infection. MYCOSES, 58, 157-157. Author URL.
Sharpe R, Thornton CR, Nikolaou V, Osborne N (2015). Higher energy efficient homes are associated with increased risk of doctor diagnosed asthma in a UK sub population. Environment International, 75, 234-244. Article has an altmetric score of 51
Thornton CR, Ryder LS, Le Cocq K, Soanes DM (2015). Identifying the emerging human pathogen Scedosporium prolificans by using a species-specific monoclonal antibody that binds to the melanin biosynthetic enzyme tetrahydroxynaphthalene reductase. Environmental Microbiology, 17(4), 1023-1048. Full text.
Bustin SA, Thornton CR, Shannon M, Agrawal SG, Lass-Floerl C, Mutschlechner W, Roberts D, Johnson G (2015). Immuno PCR-based assays for the early detection of Aspergillus species. MYCOSES, 58, 28-28. Author URL.
Thornton CR, Wills OE (2015). Immunodetection of Fungal and Oomycete Pathogens: Established and Emerging Threats to Human Health, Animal Welfare and Global Food Security. Critical Reviews in Microbiology, 41(1), 27-51. Article has an altmetric score of 1
Osborne N, Thornton CR, Sharpe R (2015). Indoor Fungi and Allergic Respiratory Disease. Current Allergy and Asthma Reports, 15, 71-71.
Sharpe RA, Bearman N, Thornton CR, Husk K, Osborne NJ (2015). Indoor fungal diversity and asthma: a meta-analysis and systematic review of risk factors. Journal of Allergy and Clinical Immunology, 135(1), 110-122. Abstract. Article has an altmetric score of 44
Sharpe RA, Bearman N, Thornton CR, Husk K, Osborne NJ (2015). Indoor fungal diversity and asthma: a metaanalysis and systematic review of risk factors. Journal of Allergy and Clinical Immunology, 135(1), 110-122. Article has an altmetric score of 44
Eigl S, Prattes J, Reinwald M, Thornton CR, Reischies F, Spiess B, Neumeister P, Zollner-Schwetz I, Raggam RB, Flick H, et al (2015). Influence of Mould-active Antifungal Treatment on the Performance of the Aspergillus specific Bronchoalveolar Lavage Lateral-Flow Device Test. International Journal of Antimicrobial Agents, 46, 401-405. Article has an altmetric score of 2
Eigl S, Prattes J, Lackner M, Willinger B, Spiess B, Selitsch B, Meilinger M, Reischies F, Neumeister P, Wolfler A, et al (2015). Multicenter evaluation of a Lateral-Flow Device Test for Diagnosing Invasive Pulmonary Aspergillosis in ICU Patients. Critical Care, 19, 1-9. Full text
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