Professor Paul Denny, BSc (Hons), PhD

Contact Professor Paul Denny (email at p.w.denny@durham.ac.uk)

Biography

Protozoan parasites are the causative agents of a wide range of important human and animal diseases, including malaria. Current work in Paul's laboratory is focused on furthering the understanding of the role of lipid biosynthesis and membrane trafficking in host-pathogen interactions, with a view to elucidating protozoan specific activities amenable to therapeutic intervention. Previous to his appointment in 2004 Paul worked in research posts at Imperial College London and at the Medical Research Council's National Institute for Medical Research.

1. Protozoan sphingolipid biosynthesis (with Prof Ehmke Pohl and others)

2. Antileishmanial discovery (with Prof Patrick Steel and others)

3. Antileishmanial mode of action deconvolution (with GSK and others)

Research Groups

Department of Biosciences

• Biomolecular Interactions

Wolfson Research Institute for Health and Wellbeing

• Centre for Global Infectious Disease
• Global Health Special Interest Group

Research Interests

• Cell Biology
• Lipid Biochemistry
• Molecular Biology
• Parasitology

Indicators of Esteem

• 2018: Editorial Board Member, Parasitology (CUP):
• 2018: Invited Presentation: CSIR-IICB TRUE, Kolkata, India
• 2018: Invited Presentation: CSIR-CDRI, Lucknow, India
• 2018: Key Note Address: CSIR-IICB, Jadavpur Campus, Kolkata, India
• 2016: Elected Office: Honorary Treasurer of Council of British Society for Parasitology (2016-19)
• 2013: Elected Office: Member of Council of British Society for Parasitology
• 2013: Invited Review: The utility of yeast as a tool for cell-based, target-directed high-throughput screening, J.L. Norcliffe, E. Alvarez-Ruiz, J.J. Martin-Plaza, P.G. Steel, P.W. Denny
• 2012: Guest Editor: Special edition of Biochemistry Research International: Lipid Metabolism as a Therapeutic Target
• 2012: Presentation at International Meeting: Screening for inhibitors of the Leishmania IPC synthase, BSP-RSC Emerging Paradigms in Anti-Infective Drug Design, LSHTM London (September 2012)
• 2011: Invited Presentation: Open Lab Foundation, Governing Board Meeting, GSK Tres Cantos, Madrid
• 2011: Invited Seminar: Spingolipid synthesis and scavenging in the parasitic protozoa (June 2011), Institut für Virologie, Zentrum für Hygiene und Infektionsbiologie, Philipps-Universität Marburg

Publications

Journal Article

• Mina, John G. M., Charlton, Rebecca L., Alpizar-Sosa, Edubiel, Escrivani, Douglas O., Brown, Christopher, Alqaisi, Amjed, Borsodi, Maria Paula G., Figueiredo, Claudia P., de Lima, Emanuelle V., Dickie, Emily A., Wei, Wenbin, Coutinho-Silva, Robson, Merritt, Andy, Smith, Terry K., Barrett, Michael P., Rossi-Bergmann, Bartira, Denny, Paul W. & Steel, Patrick G. (2021). Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the Leishmania Inositol Phosphorylceramide Synthase. ACS Infectious Diseases 7(1): 47-63.
• Denny, Paul W. & Kalesh, Karunakaran (2021). How can proteomics overhaul our understanding of Leishmania biology?. Expert Review of Proteomics
• Anderson, O., Beckett, J., Briggs, C.C., Natrass, L.A., Cranston, C.F., Wilkinson, E.J., Owen, J.H., Williams, R.M., Loukaidis, A., Bouillon, M.E., Pritchard, D., Lahmann, M., Baird, M.S. & Denny, P.W. (2020). An investigation of the antileishmanial properties of semi-synthetic saponins. RSC Medicinal Chemistry 11(7): 833-842.
• Faridnia, Roghiyeh, Kalani, Hamed, Hezarjaribi, Hajar Ziaei, Denny, Paul W., Rafie, Alireza, Fakhar, Mahdi & Virgilio, Stela (2020). Apoptotic blebs from Leishmania major-infected macrophages as a new approach for cutaneous leishmaniasis vaccination. Microbial Pathogenesis 147: 104406.
• Kalesh, Karunakaran & Denny, Paul W (2019). A BONCAT-iTRAQ method enables temporally resolved quantitative profiling of newly synthesised proteins in Leishmania mexicana parasites during starvation. PLoS Neglected Tropical Diseases 13(12): e0007651.
• Pinneh, E.C., Stoppel, R., Knight, H., Knight, M.R., Steel, P.G. & Denny, P.W. (2019). Expression levels of inositol phosphorylceramide synthase modulate plant responses to biotic and abiotic stress in Arabidopsis thaliana. PLoS ONE 14(5): e0217087.
• Britt, Hannah M., García-Herrero, Clara A., Denny, Paul W., Mosely, Jackie A. & Sanderson, John M. (2019). Lytic reactions of drugs with lipid membranes. Chemical Science 10(3): 674-680.
• Mbekeani, A.J., Jones, R.S., Bassas Llorens, M., Elliot, J., Regnault, C., Barrett, M.P., Steele, J., Kebede, B., Wrigley, S.K., Evans, L. & Denny, P.W. (2019). Mining for natural product antileishmanials in a fungal extract library. International Journal for Parasitology: Drugs and Drug Resistance 11: 118-128.
• Pinneh, E.C., Mina, J.G., Stark, M.J.R., Lindell, S.D., Luemmen, P., Knight, M.R., Steel, P.G. & Denny, P.W. (2019). The identification of small molecule inhibitors of the plant inositol phosphorylceramide synthase which demonstrate herbicidal activity. Scientific Reports 9: 8083.
• Armitage, E.G., Alqaisi, A.Q.I., Godzien, J., Pena, I., Mbekeani, A.J., Alsonso-Herranz, V., Lopez-Gonzalvez, A., Martin, J., Gabarro, R., Denny, P.W., Barrett, M.P. & Barbas, C. (2018). A complex interplay between sphingolipid and sterol metabolism revealed by perturbations to the Leishmania metabolome caused by miltefosine. Antimicrobial Agents and Chemotherapy 62(5): e02095-17.
• Mina, J.G. & Denny, P.W. (2018). Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis. Parasitology 145(2): 134-147.
• Mbekeani, A.J., Stanley, W.A., Kalel, V.C., Dohan, N., Zalckvar, E., Scheiner, L. Schliebs, W., Erdmann, R., Pohl, E. & Denny, P.W. (2018). Functional analyses of a putative, membrane-bound, peroxisomal import mechanism from the apicomplexan protozoan Toxoplasma gondii. Genes 9(9): 434.
• Norcliffe, J.L., Mina, J.G., Alvarez-Ruiz, E., Cantizani-Perez, J., de Dios-Anton, F., Colmenarejo, G., Gonzalez-Del Valle, S., Marco-Martin, M., Fiandor, J.M., Martin-Plaza, J.J., Steel, P.G. & Denny, P.W. (2018). Identifying inhibitors of the Leishmania inositol phosphorylceramide synthase with antiprotozoal activity using a yeast-based assay and ultra-high throughput screening platform. Scientific Reports 8: 3938.
• Denny, P.W. (2018). Microbial protein targets: towards understanding and intervention. Parasitology 145(2): 111-115.
• Charlton, Rebecca, Rossi-Bergmann, Bartira, Denny, Paul W. & Steel, Patrick G. (2018). Repurposing as a Strategy for the Discovery of New Anti-Leishmanials: The-State-of-the-Art. Parasitology 145(2): 219-236.
• Trinconi, Cristiana T., Miguel, Danilo C., Silber, Ariel M., Brown, Christopher, Mina, John G.M., Denny, Paul W., Heise, Norton & Uliana, Silvia R.B. (2018). Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania. International Journal for Parasitology: Drugs and Drug Resistance 8(3): 475-487.
• Alqaisi, A.Q.I., Mbekeani, A.J., Bassas Llorens, M., Elhammer, A.P. & Denny, P.W. (2018). The antifungal Aureobasidin A and an analogue are active against the protozoan parasite Toxoplasma gondii but do not inhibit sphingolipid biosynthesis. Parasitology 145(2): 148-155.
• Denny, Paul W. (2018). Yeast: bridging the gap between phenotypic and biochemical assays for high-throughput screening. Expert Opinion on Drug Discovery 13(12): 1153-1160.
• Mina, John, Thye, Julie, Alqaisi, Amjed, Bird, Louise, Dods, Robert, Groftehauge, Morten, Mosely, Jackie, Pratt, Steven, Shams-Eldin, Hosam, Schwarz, Ralph, Pohl, Ehmke & Denny, Paul W. (2017). Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites. Journal of Biological Chemistry 292(29): 12208-12219.
• Bolt, H.L., Denny, P.W. & Cobb, S.L. (2016). An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity. Journal of Visualized Experiments 117: e54750.
• Bolt, H.L., Eggimann, G.A., Denny, P.W. & Cobb, S.L. (2016). Enlarging the chemical space of anti-leishmanials: a structure-activity relationship study of peptoids against Leishmania mexicana, a causative agent of cutaneous leishmaniasis. Medicinal Chemistry Communications 7(5): 799-805.
• Grøftehauge, M.K., Truan, D., Vasil, A., Denny, P.W., Vasil, M.L. & Pohl, E. (2015). Crystal Structure of a Hidden Protein, YcaC, a Putative Cysteine Hydrolase from Pseudomonas aeruginosa, with and without an Acrylamide Adduct. International Journal of Molecular Sciences 16(7): 15971-15984.
• Eggimann, G.A., Bolt, H.L., Denny, P.W. & Cobb, S.L. (2015). Investigating the Anti-leishmanial Effects of Linear Peptoids. ChemMedChem 10(3): 233-237.
• Eggimann, G.A., Sweeney, K., Bolt, H.L., Rozatian, N., Cobb, S.L. & Denny, P.W. (2015). The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides. Molecules 20(2): 2775-2785.
• Denny, P.W. & Steel, P.G. (2015). Yeast as a Potential Vehicle for Neglected Tropical Disease Drug Discovery. Journal of Biomolecular Screening 20(1): 56-63.
• Norcliffe, J.L., Alvarez-Ruiz, E., Martin-Plaza, J.J., Steel, P.G. & Denny, P.W. (2014). The utility of yeast as a tool for cell-based, target-directed high-throughput screening. Parasitology 141(1): 8-16.
• Trmčić, M., Chadbourne, F.L., Brear, P.M., Denny, P.W., Cobb, S.L. & Hodgson, D.R.W. (2013). Aqueous synthesis of N,S,-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. Organic and Biomolecular Chemistry 11(16): 2660-2675.
• Pratt, S., Wansadhipathi-Kannangara, N.K., Bruce, C.R., Mina, J.G., Shams-Eldin, H., Casas, J., Hanada, K., Schwarz, R.T., Sonda, S. & Denny, P.W. (2013). Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii. Molecular and Biochemical Parasitology 187(1): 43-51.
• Ali, H.Z., Harding, C.R. & Denny, P.W. (2012). Endocytosis and sphingolipid scavenging in Leishmania mexicana amastigotes. Biochemistry Research International 2012: 691363.
• Smith, T.K., Reynolds, T.B. & Denny, P.W. (2012). Lipid Metabolism as a Therapeutic Target (Editorial). Biochemistry Research International 2012: 158139
• Young, S.A., Mina, J.G., Denny, P.W. & Smith, T.K. (2012). Sphingolipid and ceramide homeostasis, potential therapeutic targets. Biochemistry Research International 2012: 248135.
• Mina, J.G., Mosely, J.A., Ali, H.Z., Denny P.W. & Steel, P.G. (2011). Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain. Organic and Biomolecular Chemistry 9(6): 1823-1830.
• Featured in: Sheridan, C. (2011). Industry continues dabbling with open innovation models. Nature Biotechnology 29(12): 1063-1065.
• Chadbourne, F.L., Raleigh, C., Ali, H.Z., Denny, P.W. & Cobb, S.L. (2011). Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa. Journal of Peptide Science 17(11): 751-755.
• Mina, J.G., Mosely, J.A., Ali, H.Z., Shams-Eldin, H., Schwarz, R.T., Steel, P.G. & Denny, P.W. (2010). A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase. International Journal of Biochemistry and Cell Biology 42(9): 1553-1561.
• Cobb, S.L. & Denny, P.W. (2010). Antimicrobial peptides for leishmaniasis. Current Opinion in Investigational Drugs 11(8): 868-875.
• Mina, J.G., Okada, Y. , Wansadhipathi-Kannangara, N.K., Pratt, S., Shams-Eldin, H., Schwarz, R.T., Steel, P.G., Fawcett, T. & Denny, P.W. (2010). Functional analyses of differentially expressed isoforms of the Arabidopsis inositol phosphorylceramide synthase. Plant Molecular Biology 73(4-5): 399-407.
• Mina, J.G., Pan, S.Y., Wansadhipathi, N.K., Bruce, C., Shams-Eldin, H., Schwarz, R.T., Steel, P.G. & Denny, P.W. (2009). The Trypanosoma brucei sphingolipid synthase, an essential enzyme and drug target. Molecular And Biochemical Parasitology 168(1): 16-23.
• Featured in: In Brief (2006). Research Highlights. Nature Reviews Drug Discovery 5(9): 722.
• Denny, P. W., Shams-Eldin, H., Price, H. P., Smith, D. F. & Schwarz, R. T. (2006). The protozoan inositol phosphorylceramide synthase: A novel drug target that defines a new class of sphingolipid synthase. Journal Of Biological Chemistry 281(38): 28200-28209.

Newspaper/Magazine Article

• Rachel Brazil (2019). Are chemical engineering and biochemistry their own disciplines?. Chemistry World
• Denny, P.W. (2017). A very unpleasant 'kiss'. Microbiologist 18(4): 20-21.
• Denny, P.W. (2007). Turning up the heat on tropical disease. BBSRC Business 6.

Other (Digital/Visual Media)

• Denny, P.W. (2016). Bacteria and protozoa, chemistry and biology discussed.

Media Contacts

Available for media contact about:

• Infectious diseases: Parasites that affect both humans and animals

Supervises

• Miss Julie Thye
• Miss Frances Chadbourne
• Dr Morten Groftehauge
• Miss Sarah Smith
• Mr Paul Mason

Teaching Groups

• Medicine Phase 1