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Staff Profile: Mark Taylor

MarkProfessor Mark Taylor, B.Sc., Ph.D.

Appointment: Professor of Parasitology

Areas of interest: My area of interest is the filarial nematode diseases of humans. These include elephantiasis (lymphatic filariasis) and river blindness (onchocerciasis): two of the leading causes of global disability. My research has focused on the role of Wolbachia-bacterial endosymbionts, which have evolved a mutualistic symbiosis with the nematode that is essential for parasite development, fertility and survival. Whilst the bacteria are beneficial for the nematode, their release into the host results in inflammatory immune activation that leads to adverse events following anti-filarial treatment and contributes to the pathogenesis of river blindness and elephantiasis.

My research team have also performed laboratory and field-based studies to exploit Wolbachia as a target for antibiotic therapy, providing a novel and effective treatment for filarial infection and disease. We are also using structural, proteomic and functional genomic approaches to reveal the nature of the nematode-bacterial symbiosis to identify new targets for drug discovery and development.

Background
Mark Taylor graduated with a first class honours degree in Biological Science from the University of Plymouth in 1986 and obtained his PhD in Parasite Immunology from the University of Keele in 1989. He joined Ted Bianco's laboratory in Imperial College, London, to work on molecular vaccines for onchocerciasis where he was awarded Fellowships from the MRC and Wellcome Trust. He moved to the Liverpool School of Tropical Medicine in 1993 and developed his own independent research group through Career Development and Senior Fellowship support from the Wellcome Trust.  He is currently Head of the Molecular and Biochemical Parasitology Group and Director of AWOL.

Research

Immunology
My research is focused on the role of Wolbachia-bacterial endosymbionts in driving filarial disease pathogenesis through activation and regulation of host immunity and immunopathology. Innate immune activation by Wolbachia results in eye pathology in a model of onchocerciasis and the systemic inflammatory response associated with adverse events to anti-filarial treatment. In addition to stimulating innate responses, prior exposure to Wolbachia induces a state of tolerance to both itself and a variety of other microbial molecules, which may increase the susceptibility to opportunistic pathogens that are a feature of elephantiasis. Activation of innate immunity drives inflammatory adaptive immunity, suggesting the presence of Wolbachia may trigger the progression to chronic inflammatory disease.

Field trials
In collaboration with colleagues in Africa, Indonesia and Europe my research team have completed a series of randomised and placebo controlled field trials using doxycycline as a novel treatment against lymphatic filariasis and onchocerciasis. A course of doxycycline that depletes the bacterial endosymbionts, leads to prolonged reductions in microfilaraemia and ultimately the death of adult worms (the source of disease pathogenesis). In individuals with disease, a course of treatment can even bring about an improvement in the pathology of lymphodema and hydrocoele. This important break though has stimulated the search for new antibiotics active against the bacterial endosymbionts and has initiated a drug discovery and development programme to find anti-symbiotic drugs and treatment regimes compatible with the mass drug administration strategies of ongoing control programmes.

This breakthrough has stimulated the formation of the 'Anti-Wolbachia' (A·WOL) consortium in 2007, which is funded by the Bill & Melinda Gates Foundation to search for new drugs active against Wolbachia that are suitable for community-directed MDA (http://www.a-wol.com).

Symbiosis
Another research goal is to understand the nature of the mutualistic bacterial-nematode relationship. This is being approached by use of structural, functional genomics and proteomic analysis of the Wolbachia-nematode 'symbiome'. The aim is to identify the key molecules and pathways critical for parasite development, embryogenesis and adult worm survival.


Current grants

The Bill & Melinda Gates Foundation
Director of 'Anti-Wolbachia treatment of filariasis' consortium (A-WOL)


Recent Publications

Jump to: Article
Number of items: 56.

Halliday, Alice, Guimaraes, Ana, Tyrer, Hayley, Metuge, Haelly, Patrick, Chounna, Arnaud, Kengne-Ouafo, Kwenti, Tayong, Forsbrook, George, Steven, Andrew, Cook, Darren, Enyong, Peter, Wanji, Samuel, Taylor, Mark and Turner, Joseph (2014) 'A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis'. Parasites and Vectors, Vol 7, e472.

Tamarozzi, Francesca, Wright, Helen L, Johnston, Kelly, Edwards, Steven W, Turner, Joseph and Taylor, Mark (2014) 'Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.'. Parasite Immunology, Vol 36, Issue 10, pp. 494-502.

Johnston, Kelly, Ford, Louise and Taylor, Mark (2014) 'Overcoming the Challenges of Drug Discovery for Neglected Tropical Diseases: The AWOL Experience'. Journal of Biomolecular Screening, Vol 19, Issue 3, pp. 335-343.

Taylor, Mark, Hoerauf, Achim, Townson, Simon, Slatko, Barton E. and Ward, Stephen (2014) 'Anti-Wolbachia drug discovery and development: safe macrofilaricides for onchocerciasis and lymphatic filariasis'. Parasitology, Vol 141, Issue 01, pp. 119-127.

Goodhead, Ian, Capewell, Paul, Bailey, Wendy, Beament, Tanja, Chance, Michael, Kay, Suzanne, Forrester, Sarah, MacLeod, Annette, Taylor, Mark, Noyes, Harry and Hall, Neil (2013) 'Whole-genome sequencing of Trypanosoma brucei reveals introgression between subspecies that is associated with virulence.'. mBio, Vol 4, Issue 4, e00197-13.

More...



Selected Publications
Turner JD, Tendongfor N, Esum M, Johnston KL, Langley RS, Ford L, Faragher B, Specht S, Mand S, Hoerauf A, Enyong P, Wanji S and Taylor MJ (2010). Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial. PLOS Neglected Tropical Diseases 4: e660.

Wanji S, Tendongfor N, Nji T, Esum M, Che JN, Nkwescheu A, Alassa F, Kamnang G, Enyong PA, Taylor MJ, Hoerauf A and Taylor DW (2009).  Community-directed delivery of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis in Cameroon.  Parasites and Vectors 2: 39.

Bockarie MJ, Taylor MJ and Gyapong JO (2009).  Current practices in the management of lymphatic filariasis.  Expert Review of Anti-Infective Therapy 7: 595-605.

Turner JD, Langley RS, Johnston KL, Gentil K, Ford L, Wu B, Graham M, Sharpley F, Slatko B, Pearlman E and Taylor MJ (2009).  Wolbachia lipoprotein stimulates innate and adaptive immunity through Toll-like receptors 2 and 6 to induce disease manifestations of filariasis.  Journal of Biological Chemistry 284: 22364-22378.

Taylor MJ, Awadzi K, Basáñez MG, Biritwum N, Boakye D, Boatin B, Bockarie M, Churcher TS, Debrah A, Edwards G, Hoerauf A, Mand S, Matthews G, Osei-Atweneboana M, Prichard RK, Wanji S and Adjei O (2009).  Onchocerciasis Control: Vision for the Future from a Ghanian perspective.  Parasites and Vectors 2: 7.

Hoerauf A, Specht S, Bϋttner M, Pfarr K, Mand S, Fimmers R, Marfo-Debrekyei Y, Konadu P, Debrah AY, Bandi C, Brattig N, Albers A, Larbi J, Batsa L, Taylor MJ, Adjei O and Bϋttner DW (2008). Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study.  Medical Microbiology and Immunology 197: 295-311.

Supali T, Djuardi Y, Pfarr K M, Wibowo H, Taylor MJ, Hoerauf A, Houwing-Duistermaat JJ, Yazdanbakhsh M and Sartono E (2008). Doxycycline treatment of Brugia malayi-infected persons reduces microfilaremia and adverse reactions after diethylcarbamazine and albendazole treatment.  Clinical Infectious Diseases 46: 1385-1393.

Foster J, Kumar S, Ford L, Johnston KL, Ben R, Graeff-Teixeira C and Taylor MJ (2008). Absence of Wolbachia endobacteria in the non-filariid nematodes Angiostrongylus cantonensis and A. costaricensis. Parasites and Vectors 1: 31.

Hise AG, Daehnel K, Gillette-Ferguson I, Cho E, McGarry HF, Taylor MJ, Golenbock D , Fitzgerald KA, Kazura JW and Pearlman E (2007).  Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4, TRIF, or TRAM.  Journal of Immunology 178: 1068-1076.

Suba N, Shiny C, Taylor MJ and Narayanan RB (2007).  Brugia malayi Wolbachia hsp60 IgG antibody and isotype reactivity in different clinical groups infected or exposed to human bancroftian lymphatic filariasis. Experimental Parasitology 116: 291-295.

Gillette-Ferguson I, Hise AG, Sun Y, Diaconu E, McGarry HF, Taylor MJ and Pearlman E (2006).  Wolbachia- and Onchocerca volvulus-induced keratitis (River Blindness) is dependent on myeloid differentiation factor 88. Infection and Immunity 74: 2442-2445.

Townson S, Tagboto S, McGarry HF, Egerton GL and Taylor MJ (2006).  Onchocerca parasites and Wolbachia endosymbionts: evaluation of a spectrum of antibiotic types for activity against Onchocerca gutturosa in vitro. Filaria Journal 5: 3.

Debrah AW, Mand S, Specht S, Marfo Y, Batsam L, Pfarr K, Larbi J, Lawson B, Taylor MJ, Adjei O and Hoerauf A (2006). Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in Lymphatic Filariasis. PLoS Pathogens 2: e92.

Turner JD, Langley RS, Johnston KL, Egerton GL, Wanji S and Taylor MJ (2006). Wolbachia endosymbiotic bacteria of Brugia malayi mediate macrophage tolerance to TLR and CD40 specific stimuli in a MyD88/TLR2-dependent manner. Journal of Immunology 7: 1240-1249.

Turner JD, Mand S, Debrah A, Muehlfeld J, Pfarr K, McGarry HF, Adjei O, Taylor MJ and Hoerauf A (2006). A randomised, double blind clinical trial of three week Doxycycline plus Albendazole and Ivermectin in the treatment of Wuchereria bancrofti. Clinical Infectious Diseases 42: 1081-1089.

Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S and Hoerauf A (2005). Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet 365: (9477), 2116-2121.

Gillette-Ferguson I, Hise AG, McGarry HF, Turner J, Esposito A, Sun Y, Diaconu E, Taylor MJ and Pearlman E (2004). Wolbachia-induced neutrophil activation in a mouse model of ocular onchocerciasis (river blindness). Infection and Immunity 72: 5687-5692.

McGarry HF, Egerton G and Taylor MJ (2004). Population dynamics of Wolbachia bacterial endosymbionts in Brugia malayi. Molecular and Biochemical Parasitology 135: 57-67.

McGarry HF, Pfarr K, Egerton G, Hoerauf A, Akue JP, Enyong P, Wanji S, Kläger SL, Bianco AE, Beeching NJ and Taylor MJ (2003). Evidence against Wolbachia symbiosis in Loa loa. Filaria Journal 2: 9.

Volkmann L, Fischer K, Taylor MJ and Hoerauf A (2003). Antibiotic therapy in murine filariasis (Litomosoides sigmodontis): comparative effects of doxycycline and rifampicin on Wolbachia and filarial viability. Tropical Medicine and International Health 8: 392-401.

Hoerauf A, Mand S, Volkmann L, Buttner M, Marfo-Debrekyei Y, Taylor MJ, Adjei O and Büttner DW (2003). Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and inhibition of embryogenesis in female Onchocerca worms. Microbes and Infection 5: 261-273.

Keiser PB, Reynolds SM, Awadzi K, Ottesen EA, Taylor MJ and Nutman TB (2002). Bacterial endosymbionts of Onchocerca volvulus in the pathogenesis of posttreatment reactions. Journal of Infectious Diseases 185: 805-811.

Saint Andre A, Blackwell NM, Hall LR, Hoerauf A, Brattig NW, Volkmann L, Taylor MJ, Ford L, Hise AG, Lass JH, Diaconu E and Pearlman E (2002). The role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness. Science 295(5561): 1892-1895.

Cross HF, Haarbrink M, Egerton G, Yazdanbakhsh M and Taylor MJ (2001). Severe reactions to filarial chemotherapy and release of Wolbachia endosymbionts into blood. Lancet. 358(9296): 1873-1875.

Taylor MJ, Cross HF and Bilo K (2000). Inflammatory responses induced by the filarial nematode Brugia malayi are mediated by lipopolysaccharide-like activity from endosymbiotic Wolbachia bacteria. Journal of Experimental Medicine 191: 1429-1436.

Townson S, Hutton D, Siemienska J, Hollick L, Scanlon T, Tagboto SK and Taylor MJ (2000). Antibiotics and Wolbachia in filarial nematodes: antifilarial activity of rifampicin, oxytetracycline and chloramphenicol against Onchocerca gutturosa, Onchocerca lienalis and Brugia pahangi. Annals of Tropical Medicine and Parasitology 94: 801-816.

Taylor MJ, Bilo K, Cross HF, Archer JP and Underwood AP  (1999). 16S rDNA phylogeny and ultrastructural characterization of Wolbachia intracellular bacteria of the filarial nematodes Brugia malayi, B. pahangi, and Wuchereria bancrofti. Experimental Parasitology 91: 356-361.

Selected Reviews
Johnston KL and Taylor MJ (2007). Wolbachia in filarial parasites: targets for filarial infection and disease control. Current Infectious Disease Reports 9: 55-59.

Taylor MJ, Bandi C and Hoerauf A (2005). Wolbachia bacterial endosymbionts of filarial nematodes. Advances in Parasitology 60: 245-284.

Molyneux DH, Bradley M, Hoerauf A, Kyelem D and Taylor MJ (2003). Mass drug treatment for lymphatic filariasis and onchocerciasis. Trends in Parasitology 19: 516-522.

Taylor MJ (2003). Wolbachia in the inflammatory pathogenesis of human filariasis. Annals of the New Your Academy of Science 990: 444-449.

Taylor MJ and Hoerauf A (2001). A new approach to the treatment of filariasis. Current Opinion in Infectious Diseases14: 727-731.

Taylor MJ, Cross HF, Ford L, Makunde WH, Prasad GB and Bilo K (2001). Wolbachia bacteria in filarial immunity and disease. Parasite Immunology 23: 401-409.

Taylor MJ and Hoerauf A (1999). Wolbachia bacteria of filarial nematodes. Parasitology Today 15: 437-442.

Book Chapters
Johnston KL and Taylor MJ (2006). Wolbachia and Filarial Nematode Diseases in Humans. In: Rickettsial Diseases: Old and New. Raoult D and Parola P (Eds.). Taylor and Francis Group LLC, New York, USA.

Turner JD, Foster JM, Ganatra M, Slatko BE and Taylor MJ (2006).  The role of Wolbachia in the biology and pathogenesis of filariasis. In: Insect Symbiosis, Volume 2 (Contemporary Topics in Entomology) Edited by Kostas Bourtzi, CRC Press.

Media
News - River blindness resistance fears

River blindness (onchocerciasis) is caused by a nematode worm, which is transmitted by a black fly. 14 Jun 2007
http://news.bbc.co.uk/1/hi/health/6753003.stm

News - Gates gives third disease grant
A team of scientists, led by Dr Mark Taylor, hopes to test thousands of new combinations of potential filariasis drugs. 27 Mar 2007
http://news.bbc.co.uk/1/hi/england/merseyside/6501139.stm

 

News - Pill 'defeats elephant disease'
The condition - also known as Lymphatic Filariasis - causes severe swelling in the limbs or scrotum and affects 120m people globally, mainly in the tropics. 24 Sep 2006
http://news.bbc.co.uk/1/hi/health/5369930.stm