Staff profile

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)

 

• Cell Biology
• Lipid Biochemistry
• Molecular Biology
• Parasitology

• 2023: Fellow of the Royal Society of Biology: Elected January 2023
• 2023: MRC Outstanding Team Impact Prize Winner - Lead: Global Network for NTDs The MRC Global Challenges Research Fund-funded Global Network for NTDs brought together over 500 researchers from 13 institutes around the world, via new collaborative research teams focused on Leishmaniasis and Chagas disease. The network sought to democratise and decolonise the field, through growing laboratory research capacity and expertise in endemic countries across Asia and South America. It has made significant scientific advances. Its cross-disciplinary partnerships with endemic country scientists have demonstrated globally equitable working practices. This exemplar brought in and influenced private sector collaborators, revealing the network’s most tangible legacy and impact.
• 2022: Topic Editor: Frontiers in Cellular and Infection Microbiology, section Parasite and Host

   Leishmania Genome Variability: Impacts on Parasite Evolution, Parasitism and Leishmaniases Control

• 2018: Editorial Board Member, Parasitology (CUP):
• 2018: Invited Presentation: CSIR-CDRI, Lucknow, India
• 2018: Invited Presentation: CSIR-IICB TRUE, Kolkata, 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: 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)
• 2012: Guest Editor: Special edition of Biochemistry Research International: Lipid Metabolism as a Therapeutic Target
• 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

Journal Article

• Denny, P. (online). Evaluation of the Leishmania inositol phosphorylceramide synthase as a drug target using a chemical and genetic approach. ACS Infectious Diseases,
• Koutsogiannis, Z., & Denny, P. W. (2024). Rapid genotyping of Toxoplasma gondii isolates via Nanopore-based multi-locus sequencing. AMB Express, 14(1), Article 68. https://doi.org/10.1186/s13568-024-01728-x
• Agostino, V. S., Buerdsell, M. L., Uliana, S. R. B., Denny, P. W., Coelho, A. C., & Steel, P. G. (2024). Clemastine/tamoxifen hybrids as easily accessible antileishmanial drug leads. Organic and Biomolecular Chemistry, 22(9), 1812-1820. https://doi.org/10.1039/d3ob02091f
• Koutsogiannis, Z., Mina, J. G., Albus, C. A., Kol, M. A., Holthuis, J. C. M., Pohl, E., & Denny, P. W. (2023). Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness. FASEB Journal, 37(11), Article e23229. https://doi.org/10.1096/fj.202201603RRR
• Dos Santos, N. S. A., Estevez-Castro, C. F., Macedo, J. P., Chame, D. F., Castro-Gomes, T., Santos-Cardoso, M., …Teixeira, S. M. R. (2023). Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity. PLoS Neglected Tropical Diseases, 17(9), Article e0011646. https://doi.org/10.1371/journal.pntd.0011646
• Tosi, L. R., Denny, P. W., De Oliveira, C. I., & Damasceno, J. D. (2023). Editorial: Leishmania genome variability: Impacts on parasite evolution, parasitism and leishmaniases control. Frontiers in Cellular and Infection Microbiology, 13, https://doi.org/10.3389/fcimb.2023.1171962
• Porta, E. O., Gao, L., Denny, P. W., Steel, P. G., & Kalesh, K. (2023). Inhibition of HSP90 distinctively modulates the global phosphoproteome of Leishmania mexicana developmental stages. Microbiology Spectrum, https://doi.org/10.1128/spectrum.02960-23
• Koutsogiannis, Z., Mina, J. G. M., Suman, R., & Denny, P. W. (2023). Assessment of Toxoplasma gondii lytic cycle and the impact of a gene deletion using 3D label-free optical diffraction holotomography. Frontiers in Cellular and Infection Microbiology, 13, Article 1237594. https://doi.org/10.3389/fcimb.2023.1237594
• Elsheikha, H. M., Al-Sandaqchi, A. T., Harun, M. S., Winterton, F., Altharawi, A., Elsaied, N. A., …Chan, K. L. A. (2022). Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy. Cells, 11(5), Article 811. https://doi.org/10.3390/cells11050811
• Kalesh, K., Wei, W., Mantilla, B., Roumeliotis, T., Choudhary, J., & Denny, P. (2022). Transcriptome-Wide Identification of Coding and Noncoding RNA-Binding Proteins Defines the Comprehensive RNA Interactome of Leishmania mexicana. Microbiology Spectrum, 10(1), e02422-21. https://doi.org/10.1128/spectrum.02422-21
• Alpizer-Sosa, E., Ithnin, N., Wei, W., Pountain, A., Weidt, A., Donachie, A., …Barrett, M. (2022). Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response. PLoS Neglected Tropical Diseases, 16(9), Article e0010779. https://doi.org/10.1371/journal.pntd.0010779
• Alpizar-Sosa, E., Kumordzi, Y., Wei, W., Whitfield, P., Barrett, M., & Denny, P. (2022). Genome deletions to overcome the directed loss of gene function in Leishmania. Frontiers in Cellular and Infection Microbiology, 12, https://doi.org/10.3389/fcimb.2022.988688
• Mantilla, B., Azevedo, C., Denny, P., Saiardi, A., & Docampo, R. (2021). The Histidine Ammonia Lyase of Trypanosoma cruzi is Involved in Acidocalcisome Alkalinization and is Essential for Survival under Starvation Conditions. mBio, 12(6), https://doi.org/10.1128/mbio.01981-21
• Karunakaran, K., Sundriyal, S., Perera, H., Cobb, S. L., & Denny, P. W. (2021). Quantitative Proteomics Reveals that Hsp90 Inhibition Dynamically Regulates Global Protein Synthesis in Leishmania mexicana. mSystems, https://doi.org/10.1128/msystems.00089-21
• Denny, P. W., & Karunakaran, K. (2021). How can proteomics overhaul our understanding of Leishmania biology?. Expert Review of Proteomics, https://doi.org/10.1080/14789450.2020.1885375
• Escrivani, D. O., Charlton, R. L., Caruso, M. B., Burle-Caldas, G. A., Borsodi, M. P. G., Zingali, R. B., …Steel, P. G. (2021). Chalcones identify cTXNPx as a potential antileishmanial drug target. PLoS Neglected Tropical Diseases, 15(11), Article e0009951. https://doi.org/10.1371/journal.pntd.0009951
• Mina, J. G., Charlton, R. L., Alpizar-Sosa, E., Escrivani, D. O., Brown, C., Alqaisi, A., …Steel, P. G. (2021). Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the Leishmania Inositol Phosphorylceramide Synthase. ACS Infectious Diseases, 7(1), 47-63. https://doi.org/10.1021/acsinfecdis.0c00546
• Faridnia, R., Kalani, H., Hezarjaribi, H. Z., Denny, P. W., Rafie, A., Fakhar, M., & Virgilio, S. (2020). Apoptotic blebs from Leishmania major-infected macrophages as a new approach for cutaneous leishmaniasis vaccination. Microbial Pathogenesis, 147, Article 104406. https://doi.org/10.1016/j.micpath.2020.104406
• Anderson, O., Beckett, J., Briggs, C., Natrass, L., Cranston, C., Wilkinson, E., …Denny, P. (2020). An investigation of the antileishmanial properties of semi-synthetic saponins. RSC Medicinal Chemistry, 11(7), 833-842. https://doi.org/10.1039/d0md00123f
• Mbekeani, A., Jones, R., Bassas Llorens, M., Elliot, J., Regnault, C., Barrett, M., …Denny, P. (2019). Mining for natural product antileishmanials in a fungal extract library. International Journal for Parasitology: Drugs and Drug Resistance, 11, 118-128. https://doi.org/10.1016/j.ijpddr.2019.05.003
• Karunakaran, K., & Denny, P. 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), Article e0007651. https://doi.org/10.1371/journal.pntd.0007651
• Pinneh, E., Mina, J., Stark, M., Lindell, S., Luemmen, P., Knight, M., …Denny, P. (2019). The identification of small molecule inhibitors of the plant inositol phosphorylceramide synthase which demonstrate herbicidal activity. Scientific Reports, 9, Article 8083. https://doi.org/10.1038/s41598-019-44544-1
• Pinneh, E., Stoppel, R., Knight, H., Knight, M., Steel, P., & Denny, P. (2019). Expression levels of inositol phosphorylceramide synthase modulate plant responses to biotic and abiotic stress in Arabidopsis thaliana. PLoS ONE, 14(5), Article e0217087. https://doi.org/10.1371/journal.pone.0217087
• Britt, H. M., García-Herrero, C. A., Denny, P. W., Mosely, J. A., & Sanderson, J. M. (2019). Lytic reactions of drugs with lipid membranes. Chemical Science, 10(3), 674-680. https://doi.org/10.1039/c8sc04831b
• Trinconi, C. T., Miguel, D. C., Silber, A. M., Brown, C., Mina, J. G., Denny, P. W., …Uliana, S. R. (2018). Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania. International Journal for Parasitology: Drugs and Drug Resistance, 8(3), 475-487. https://doi.org/10.1016/j.ijpddr.2018.10.007
• Denny, P. W. (2018). Yeast: bridging the gap between phenotypic and biochemical assays for high-throughput screening. Expert Opinion on Drug Discovery, 13(12), 1153-1160. https://doi.org/10.1080/17460441.2018.1534826
• Mbekeani, A., Stanley, W., Kalel, V., Dohan, N., Zalckvar, E., Scheiner, L., …Denny, P. (2018). Functional analyses of a putative, membrane-bound, peroxisomal import mechanism from the apicomplexan protozoan Toxoplasma gondii. Genes, 9(9), Article 434. https://doi.org/10.3390/genes9090434
• Armitage, E., Alqaisi, A., Godzien, J., Pena, I., Mbekeani, A., Alsonso-Herranz, V., …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. https://doi.org/10.1128/aac.02095-17
• Norcliffe, J., Mina, J., Alvarez-Ruiz, E., Cantizani-Perez, J., de Dios-Anton, F., Colmenarejo, G., …Denny, P. (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, Article 3938. https://doi.org/10.1038/s41598-018-22063-9
• Denny, P. (2018). Microbial protein targets: towards understanding and intervention. Parasitology, 145(2), 111-115. https://doi.org/10.1017/s0031182017002037
• Mina, J., & Denny, P. (2018). Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis. Parasitology, 145(2), 134-147. https://doi.org/10.1017/s0031182017001081
• Alqaisi, A., Mbekeani, A., Bassas Llorens, M., Elhammer, A., & Denny, P. (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. https://doi.org/10.1017/s0031182017000506
• Charlton, R., Rossi-Bergmann, B., Denny, P. W., & Steel, P. G. (2018). Repurposing as a Strategy for the Discovery of New Anti-Leishmanials: The-State-of-the-Art. Parasitology, 145(2), 219-236. https://doi.org/10.1017/s0031182017000993
• Mina, J., Thye, J., Alqaisi, A., Bird, L., Dods, R., Groftehauge, M., …Denny, P. 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. https://doi.org/10.1074/jbc.m117.792374
• Bolt, H., Denny, P., & Cobb, S. (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, Article e54750. https://doi.org/10.3791/54750
• Bolt, H., Eggimann, G., Denny, P., & Cobb, S. (2016). Enlarging the chemical space of anti-leishmanials: a structure-activity relationship study of peptoids against Leishmania mexicana, a causative agent of cutaneous leishmaniasis. MedChemComm, 7(5), 799-805. https://doi.org/10.1039/c6md00060f
• Grøftehauge, M., Truan, D., Vasil, A., Denny, P., Vasil, M., & 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. https://doi.org/10.3390/ijms160715971
• Eggimann, G., Sweeney, K., Bolt, H., Rozatian, N., Cobb, S., & Denny, P. (2015). The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides. Molecules, 20(2), 2775-2785. https://doi.org/10.3390/molecules20022775
• Eggimann, G., Bolt, H., Denny, P., & Cobb, S. (2015). Investigating the Anti-leishmanial Effects of Linear Peptoids. ChemMedChem, 10(3), 233-237. https://doi.org/10.1002/cmdc.201402416
• Denny, P., & Steel, P. (2015). Yeast as a Potential Vehicle for Neglected Tropical Disease Drug Discovery. Journal of biomolecular screening, 20(1), 56-63. https://doi.org/10.1177/1087057114546552
• Norcliffe, J., Alvarez-Ruiz, E., Martin-Plaza, J., Steel, P., & Denny, P. (2014). The utility of yeast as a tool for cell-based, target-directed high-throughput screening. Parasitology, 141(1), 8-16. https://doi.org/10.1017/s0031182013000425
• Pratt, S., Wansadhipathi-Kannangara, N., Bruce, C., Mina, J., Shams-Eldin, H., Casas, J., …Denny, P. (2013). Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii. Molecular and Biochemical Parasitology, 87(1), 43-51. https://doi.org/10.1016/j.molbiopara.2012.11.007
• Trmčić, M., Chadbourne, F., Brear, P., Denny, P., Cobb, S., & Hodgson, D. (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. https://doi.org/10.1039/c3ob27448a
• Young, S., Mina, J., Denny, P., & Smith, T. (2012). Sphingolipid and ceramide homeostasis, potential therapeutic targets. Biochemistry Research International, 2012, Article 248135. https://doi.org/10.1155/2012/248135
• Smith, T., Reynolds, T., & Denny, P. (2012). Lipid Metabolism as a Therapeutic Target (Editorial). Biochemistry Research International, 2012, Article 158139. https://doi.org/10.1155/2012/158139
• Ali, H., Harding, C., & Denny, P. (2012). Endocytosis and sphingolipid scavenging in Leishmania mexicana amastigotes. Biochemistry Research International, 2012, Article 691363. https://doi.org/10.1155/2012/691363
• Chadbourne, F., Raleigh, C., Ali, H., Denny, P., & Cobb, S. (2011). Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa. Journal of Peptide Science, 17(11), 751-755. https://doi.org/10.1002/psc.1398
• Mina, J., Mosely, J., Ali, H., Denny, P., & Steel, P. (2011). Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain. Organic and Biomolecular Chemistry, 9(6), 1823-1830. https://doi.org/10.1039/c0ob00871k
• innovation models. Nature Biotechnology, 29(12), 1063-1065. https://doi.org/10.1038/nbt1211-1063a
• Mina, J., Mosely, J., Ali, H., Shams-Eldin, H., Schwarz, R., Steel, P., & Denny, P. (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. https://doi.org/10.1016/j.biocel.2010.06.008
• Cobb, S., & Denny, P. (2010). Antimicrobial peptides for leishmaniasis. Current opinion in investigational drugs, 11(8), 868-875
• Mina, J., Okada, Y., Wansadhipathi-Kannangara, N., Pratt, S., Shams-Eldin, H., Schwarz, R., …Denny, P. (2010). Functional analyses of differentially expressed isoforms of the Arabidopsis inositol phosphorylceramide synthase. Plant Molecular Biology, 73(4-5), 399-407. https://doi.org/10.1007/s11103-010-9626-3
• Mina, J., Pan, S., Wansadhipathi, N., Bruce, C., Shams-Eldin, H., Schwarz, R., …Denny, P. (2009). The Trypanosoma brucei sphingolipid synthase, an essential enzyme and drug target. Molecular and Biochemical Parasitology, 168(1), 16-23. https://doi.org/10.1016/j.molbiopara.2009.06.002
• Denny, P., Shams-Eldin, H., Price, H., Smith, D., & Schwarz, R. (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. https://doi.org/10.1074/jbc.m600796200
• Denny, P. (2006). Research Highlights. Nature Reviews Drug Discovery, 5(9), https://doi.org/10.1038/nrd2143

Newspaper/Magazine Article

• Denny, P. (2021). How an equal partnership can lead to big breakthroughs in NTDs research

Other (Digital/Visual Media)

• Denny, P. (2016). Bacteria and protozoa, chemistry and biology discussed. [[Media unknown]]

Other (Print)

• Brazil, R. (2019). Are chemical engineering and biochemistry their own disciplines?
• Denny, P. (2017). A very unpleasant 'kiss'
• Denny, P. (2007). Turning up the heat on tropical disease

Patent

• Denny, P., Steel, P., & Lyne, V. (2024). TREATMENT OF LEISHMANIASIS. WO 2024/084186 A1