![Josie Parker](https://profiles-cardiff.imgix.net/attachments/1153?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Josie Parker
Darlithydd mewn Biocemeg (T&R)
Ysgol y Biowyddorau
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwyg
Cytochrome P450s (CYPs)
CYPs are haem containing enzymes that are essential enzymes in many pathways but can also be involved in secondary metabolism in some organisms. They are targeted by inhibitors such as antifungal and chemotherapy agents and their capabilities can be harvested for biotechnology. I study the targeting of CYPs by inhibitors in medical and agricultural applications and investigate their physiological function. In particular my research has led to discoveries in antifungal resistance and the treatment of fungal infections in both medicine and agriculture.
I am particularly interested in the function of CYPs in infectious diseases and as ‘druggable’ targets and am also interested in the production of drugs, antibiotics and high value chemicals with biotechnological applications using these enzymes.
Cyhoeddiad
2024
- Navarro-Mendoza, M. I., Perez-Arques, C., Parker, J., Xu, Z., Kelly, S. and Heitman, J. 2024. Alternative ergosterol biosynthetic pathways confer antifungal drug resistance in the human pathogens within the Mucor species complex. mBio 15(8), article number: e01661-24. (10.1128/mbio.01661-24)
- O'Connor-Moneley, J., Fletcher, J., Bean, C., Parker, J., Kelly, S. L., Moran, G. P. and Sullivan, D. J. 2024. Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance. PLoS ONE 19(8), article number: e0308665. (10.1371/journal.pone.0308665)
- Xie, J. et al. 2024. The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species. Nature Communications 15, article number: 4261. (10.1038/s41467-024-48767-3)
- Rybak, J. M. et al. 2024. A secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1. Nature Communications 15, article number: 3642. (10.1038/s41467-024-48029-2)
- Ollinger, T. L., Zarnowski, R., Parker, J. E., Kelly, S. L., Andes, D. R., Stamnes, M. A. and Krysan, D. J. 2024. Genetic interaction analysis of Candida glabrata transcription factors CST6 and UPC2A in the regulation of respiration and fluconazole susceptibility. Antimicrobial Agents and Chemotherapy
2023
- Asadzadeh, M. et al. 2023. Molecular characterization and sterol profiles identify nonsynonymous mutations in ERG2 as a major mechanism conferring reduced susceptibility to amphotericin B in candida kefyr. Microbiology Spectrum 11(4), article number: e01474-23. (10.1128/spectrum.01474-23)
2022
- Rybak, J. M. et al. 2022. In vivo emergence of high-level resistance during treatment reveals the first identified mechanism of amphotericin B resistance in Candida auris. Clinical Microbiology and Infection 28(6), pp. 838-843. (10.1016/j.cmi.2021.11.024)
- Regan, J. et al. 2022. Titration of C-5 Sterol Desaturase Activity Reveals Its Relationship to Candida albicans Virulence and Antifungal Susceptibility Is Dependent upon Host Immune Status. mBio 13(2) (10.1128/mbio.00115-22)
- Price, C. L. et al. 2022. Cytochrome P450 168A1 from pseudomonas aeruginosa is involved in the hydroxylation of biologically relevant fatty acids. PLoS ONE 17(3), pp. 1-20., article number: e0265227. (10.1371/journal.pone.0265227)
2021
- Olinger, T. L. et al. 2021. Loss-of-function ROX1 mutations suppress the fluconazole susceptibility of upc2AΔ mutation in Candida glabrata, implicating additional positive regulators of Ergosterol biosynthesis. mSphere 6(6), article number: e00830-21. (10.1128/msphere.00830-21)
- Luna-Tapia, A., Parker, J. E., Kelly, S. L. and Palmer, G. E. 2021. Species-specific differences in C-5 sterol desaturase function influence the outcome of azole antifungal exposure. Antimicrobial Agents and Chemotherapy 65(12), article number: e01044. (10.1128/aac.01044-21)
- Aruanno, M. et al. 2021. Insights in the molecular mechanisms of an azole stress adapted laboratory-generated Aspergillus fumigatus strain. Medical Mycology 59(8), pp. 763-772. (10.1093/mmy/myaa118)
2020
- Binjubair, F. A. et al. 2020. Small‐molecule inhibitors targeting sterol 14α‐Demethylase (CYP51): synthesis, molecular modelling and evaluation against Candida albicans. ChemMedChem 15(14), pp. 1294-1309., article number: Volume15, Issue14 July 20, 2020 Pages 1294-1309. (10.1002/cmdc.202000250)
- Rybak, J. M. et al. 2020. Mutations in TAC1B: a novel genetic determinant of clinical fluconazole resistance in Candida auris. mBio 11(3), article number: e00365-20. (10.1128/mBio.00365-20)
- Morgan, S. R. et al. 2020. Controlled in vitro delivery of voriconazole and diclofenac to the cornea using contact lenses for the treatment of Acanthamoeba keratitis. International Journal of Pharmaceutics 579, article number: 119102. (10.1016/j.ijpharm.2020.119102)
- Furukawa, T. et al. 2020. The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus. Nature Communications 11(1), article number: 427. (10.1038/s41467-019-14191-1)
2019
- Kannan, A., Asner, S. A., Trachsel, E., Kelly, S., Parker, J., Sanglard, D. and Heitman, J. 2019. Comparative genomics for the elucidation of multidrug resistance in Candida lusitaniae. mBio 10(6), article number: e02512-19. (10.1128/mBio.02512-19)
- Warrilow, A. G., Parker, J. E., Price, C. L., Rolley, N. J., Nes, W. D., Kelly, D. E. and Kelly, S. L. 2019. Isavuconazole and voriconazole inhibition of sterol 14α-demethylases (CYP51) from Aspergillus fumigatus and Homo sapiens. International Journal of Antimicrobial Agents 54(4), pp. 449-455. (10.1016/j.ijantimicag.2019.07.011)
- Rybak, J. M. et al. 2019. Mutations in hmg1, challenging the paradigm of clinical triazole resistance in Aspergillus fumigatus. mBio 10(2), article number: e00437-19. (10.1128/mBio.00437-19)
- Warrilow, A. G. et al. 2019. The evolution of azole resistance in Candida albicans sterol 14α-demethylase (CYP51) through incremental amino acid substitutions. Antimicrobial Agents and Chemotherapy 63(5), article number: e02586-18. (10.1128/AAC.02586-18)
- Griffiths, W. J. et al. 2019. Additional pathways of sterol metabolism: evidence from analysis of Cyp27a1-/- mouse brain and plasma. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1864(2), pp. 191-211. (10.1016/j.bbalip.2018.11.006)
2018
- Ahmad, S., Joseph, L., Parker, J. E., Asadzadeh, M., Kelly, S. L., Meis, J. F. and Khan, Z. 2018. ERG6 and ERG2 are major targets conferring reduced susceptibility to amphotericin B in clinical Candida glabrata isolates in Kuwait. Antimicrobial Agents and Chemotherapy 63(2), article number: e01900-18. (10.1128/AAC.01900-18)
- Zhou, W. et al. 2018. Functional importance for developmental regulation of sterol biosynthesis in Acanthamoeba castellanii. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1863(10), pp. 1164-1178. (10.1016/j.bbalip.2018.07.004)
- Luna-Tapia, A. et al. 2018. Loss of Upc2p-inducible Erg3 transcription is sufficient to confer niche-specific azole resistance without compromising Candida albicans pathogenicity. mBio 9(3), article number: e00225-18. (10.1128/mBio.00225-18)
- Colley, T. et al. 2018. In vitro and in vivo efficacy of a novel and long-acting fungicidal azole, PC1244, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy 62(5), article number: e01941-17. (10.1128/AAC.01941-17)
2017
- Butts, A. et al. 2017. Target abundance-based fitness screening (TAFiS) facilitates rapid identification of target-specific and physiologically active chemical probes. mSphere 2(5), article number: e00379-17. (10.1128/mSphere.00379-17)
- Rybak, J. M. et al. 2017. Loss of C-5 sterol desaturase activity results in increased resistance to azole and echinocandin antifungals in a clinical isolate of Candida parapsilosis. Antimicrobial Agents and Chemotherapy 61(9), article number: e00651-17. (10.1128/AAC.00651-17)
- Colley, T. et al. 2017. In vitro and in vivo antifungal profile of a novel and long-acting inhaled azole, PC945, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy 61(5), article number: e02280-16. (10.1128/AAC.02280-16)
2016
- McCourt, P. et al. 2016. Proper sterol distribution is required for Candida albicans hyphal formation and virulence. G3: Genes | Genomes | Genetics 6(11), pp. 3455-3465. (10.1534/g3.116.033969)
- Warrilow, A. G. S. et al. 2016. The investigational drug VT-1129 is a highly potent inhibitor of Cryptococcus species CYP51 but only weakly inhibits the human enzyme. Antimicrobial Agents and Chemotherapy 60(8), pp. 4530-4538. (10.1128/AAC.00349-16)
- Warrilow, A. G. S. et al. 2016. Azole antifungal sensitivity of sterol 14α-demethylase (cyp51) and cyp5218 from Malassezia globosa. Scientific Reports 6(1), article number: 27690. (10.1038/srep27690)
Erthyglau
- Navarro-Mendoza, M. I., Perez-Arques, C., Parker, J., Xu, Z., Kelly, S. and Heitman, J. 2024. Alternative ergosterol biosynthetic pathways confer antifungal drug resistance in the human pathogens within the Mucor species complex. mBio 15(8), article number: e01661-24. (10.1128/mbio.01661-24)
- O'Connor-Moneley, J., Fletcher, J., Bean, C., Parker, J., Kelly, S. L., Moran, G. P. and Sullivan, D. J. 2024. Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance. PLoS ONE 19(8), article number: e0308665. (10.1371/journal.pone.0308665)
- Xie, J. et al. 2024. The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species. Nature Communications 15, article number: 4261. (10.1038/s41467-024-48767-3)
- Rybak, J. M. et al. 2024. A secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1. Nature Communications 15, article number: 3642. (10.1038/s41467-024-48029-2)
- Ollinger, T. L., Zarnowski, R., Parker, J. E., Kelly, S. L., Andes, D. R., Stamnes, M. A. and Krysan, D. J. 2024. Genetic interaction analysis of Candida glabrata transcription factors CST6 and UPC2A in the regulation of respiration and fluconazole susceptibility. Antimicrobial Agents and Chemotherapy
- Asadzadeh, M. et al. 2023. Molecular characterization and sterol profiles identify nonsynonymous mutations in ERG2 as a major mechanism conferring reduced susceptibility to amphotericin B in candida kefyr. Microbiology Spectrum 11(4), article number: e01474-23. (10.1128/spectrum.01474-23)
- Rybak, J. M. et al. 2022. In vivo emergence of high-level resistance during treatment reveals the first identified mechanism of amphotericin B resistance in Candida auris. Clinical Microbiology and Infection 28(6), pp. 838-843. (10.1016/j.cmi.2021.11.024)
- Regan, J. et al. 2022. Titration of C-5 Sterol Desaturase Activity Reveals Its Relationship to Candida albicans Virulence and Antifungal Susceptibility Is Dependent upon Host Immune Status. mBio 13(2) (10.1128/mbio.00115-22)
- Price, C. L. et al. 2022. Cytochrome P450 168A1 from pseudomonas aeruginosa is involved in the hydroxylation of biologically relevant fatty acids. PLoS ONE 17(3), pp. 1-20., article number: e0265227. (10.1371/journal.pone.0265227)
- Olinger, T. L. et al. 2021. Loss-of-function ROX1 mutations suppress the fluconazole susceptibility of upc2AΔ mutation in Candida glabrata, implicating additional positive regulators of Ergosterol biosynthesis. mSphere 6(6), article number: e00830-21. (10.1128/msphere.00830-21)
- Luna-Tapia, A., Parker, J. E., Kelly, S. L. and Palmer, G. E. 2021. Species-specific differences in C-5 sterol desaturase function influence the outcome of azole antifungal exposure. Antimicrobial Agents and Chemotherapy 65(12), article number: e01044. (10.1128/aac.01044-21)
- Aruanno, M. et al. 2021. Insights in the molecular mechanisms of an azole stress adapted laboratory-generated Aspergillus fumigatus strain. Medical Mycology 59(8), pp. 763-772. (10.1093/mmy/myaa118)
- Binjubair, F. A. et al. 2020. Small‐molecule inhibitors targeting sterol 14α‐Demethylase (CYP51): synthesis, molecular modelling and evaluation against Candida albicans. ChemMedChem 15(14), pp. 1294-1309., article number: Volume15, Issue14 July 20, 2020 Pages 1294-1309. (10.1002/cmdc.202000250)
- Rybak, J. M. et al. 2020. Mutations in TAC1B: a novel genetic determinant of clinical fluconazole resistance in Candida auris. mBio 11(3), article number: e00365-20. (10.1128/mBio.00365-20)
- Morgan, S. R. et al. 2020. Controlled in vitro delivery of voriconazole and diclofenac to the cornea using contact lenses for the treatment of Acanthamoeba keratitis. International Journal of Pharmaceutics 579, article number: 119102. (10.1016/j.ijpharm.2020.119102)
- Furukawa, T. et al. 2020. The negative cofactor 2 complex is a key regulator of drug resistance in Aspergillus fumigatus. Nature Communications 11(1), article number: 427. (10.1038/s41467-019-14191-1)
- Kannan, A., Asner, S. A., Trachsel, E., Kelly, S., Parker, J., Sanglard, D. and Heitman, J. 2019. Comparative genomics for the elucidation of multidrug resistance in Candida lusitaniae. mBio 10(6), article number: e02512-19. (10.1128/mBio.02512-19)
- Warrilow, A. G., Parker, J. E., Price, C. L., Rolley, N. J., Nes, W. D., Kelly, D. E. and Kelly, S. L. 2019. Isavuconazole and voriconazole inhibition of sterol 14α-demethylases (CYP51) from Aspergillus fumigatus and Homo sapiens. International Journal of Antimicrobial Agents 54(4), pp. 449-455. (10.1016/j.ijantimicag.2019.07.011)
- Rybak, J. M. et al. 2019. Mutations in hmg1, challenging the paradigm of clinical triazole resistance in Aspergillus fumigatus. mBio 10(2), article number: e00437-19. (10.1128/mBio.00437-19)
- Warrilow, A. G. et al. 2019. The evolution of azole resistance in Candida albicans sterol 14α-demethylase (CYP51) through incremental amino acid substitutions. Antimicrobial Agents and Chemotherapy 63(5), article number: e02586-18. (10.1128/AAC.02586-18)
- Griffiths, W. J. et al. 2019. Additional pathways of sterol metabolism: evidence from analysis of Cyp27a1-/- mouse brain and plasma. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1864(2), pp. 191-211. (10.1016/j.bbalip.2018.11.006)
- Ahmad, S., Joseph, L., Parker, J. E., Asadzadeh, M., Kelly, S. L., Meis, J. F. and Khan, Z. 2018. ERG6 and ERG2 are major targets conferring reduced susceptibility to amphotericin B in clinical Candida glabrata isolates in Kuwait. Antimicrobial Agents and Chemotherapy 63(2), article number: e01900-18. (10.1128/AAC.01900-18)
- Zhou, W. et al. 2018. Functional importance for developmental regulation of sterol biosynthesis in Acanthamoeba castellanii. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1863(10), pp. 1164-1178. (10.1016/j.bbalip.2018.07.004)
- Luna-Tapia, A. et al. 2018. Loss of Upc2p-inducible Erg3 transcription is sufficient to confer niche-specific azole resistance without compromising Candida albicans pathogenicity. mBio 9(3), article number: e00225-18. (10.1128/mBio.00225-18)
- Colley, T. et al. 2018. In vitro and in vivo efficacy of a novel and long-acting fungicidal azole, PC1244, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy 62(5), article number: e01941-17. (10.1128/AAC.01941-17)
- Butts, A. et al. 2017. Target abundance-based fitness screening (TAFiS) facilitates rapid identification of target-specific and physiologically active chemical probes. mSphere 2(5), article number: e00379-17. (10.1128/mSphere.00379-17)
- Rybak, J. M. et al. 2017. Loss of C-5 sterol desaturase activity results in increased resistance to azole and echinocandin antifungals in a clinical isolate of Candida parapsilosis. Antimicrobial Agents and Chemotherapy 61(9), article number: e00651-17. (10.1128/AAC.00651-17)
- Colley, T. et al. 2017. In vitro and in vivo antifungal profile of a novel and long-acting inhaled azole, PC945, on Aspergillus fumigatus infection. Antimicrobial Agents and Chemotherapy 61(5), article number: e02280-16. (10.1128/AAC.02280-16)
- McCourt, P. et al. 2016. Proper sterol distribution is required for Candida albicans hyphal formation and virulence. G3: Genes | Genomes | Genetics 6(11), pp. 3455-3465. (10.1534/g3.116.033969)
- Warrilow, A. G. S. et al. 2016. The investigational drug VT-1129 is a highly potent inhibitor of Cryptococcus species CYP51 but only weakly inhibits the human enzyme. Antimicrobial Agents and Chemotherapy 60(8), pp. 4530-4538. (10.1128/AAC.00349-16)
- Warrilow, A. G. S. et al. 2016. Azole antifungal sensitivity of sterol 14α-demethylase (cyp51) and cyp5218 from Malassezia globosa. Scientific Reports 6(1), article number: 27690. (10.1038/srep27690)
Ymchwil
Molecular investigation of Cytochrome P450s (CYPs) and antifungal resistance
My research is focused on Cytochrome P450s (CYPs) and antifungal resistance.
Cytochrome P450 (CYPs) are haem containing enzymes. Several thousand CYP proteins have been identified belonging to hundreds of different families. Some have essential roles in metabolism (for example in the production of sterols and steroid hormones) and in the biotransformation of drugs and xenobiotics (such as those CYPs in mammalian livers). In bacteria and fungi some P450s have been found to be essential for growth on unusual carbon sources, such as camphor and alkanes. They are also involved in secondary metabolism and the production of important natural products such as antibiotics and virulence factors such as siderophores in microorganisms.
The essentiality of some CYPs in metabolic pathways has been exploited for the use of chemotherapy, including the target of azole antifungals and the target for aromatase inhibitors in cancer treatment. CYPs therefore present an attractive good ‘druggable’ targets, their interaction with inhibitors is well understood and they may be useful for targeting other diseases in the future.
Some prokaryotic species have very large numbers of CYPs and the function of many of them is not yet known or understood. Research on CYPs aids the understanding of infection/virulence, resistance to existing antimicrobial drugs and the means to produce new antimicrobial drugs. In addition, as the physiological functions of CYPs are resolved there is the possibility that they will provide new antimicrobial targets in infectious organisms.
Research in my laboratory is currently centred on two main themes:
- Understanding the molecular basis of azole resistance in fungal infections
- Investigating the physiological role of CYPs of ‘unknown function’ in microorganisms
Addysgu
- BI1001 Skills for Science
- BI1014 Biological Chemistry
- BI1051 Genetics and Evolution (Recombinant DNA Technology)
Fellow of the Higher Education Academy
Bywgraffiad
I studied for my Genetics undergraduate degree at the University of Wales, Aberystwyth and went on to complete a PhD on microbial cytochrome P450s in 2006. During my time as a postdoctoral researcher at Swansea University (2005-2021) I worked on a variety of projects involving the structure and function of cytochrome P450s. In particular I studied drug targets and associated enzymes - investigating the mechanisms of antifungal resistance in both medical and agricultural disease and novel antifungal compounds for the treatment of drug-resistant infections.
I moved to Cardiff University as a Lecturer in July 2022.
Aelodaethau proffesiynol
- Aelod o'r Gymdeithas Frenhinol Bioleg
- Aelod o'r Gymdeithas Biocemegol
- Aelod o'r Gymdeithas Microbioleg
- Aelod o Gymdeithas Cemotherapi Gwrthficrobaidd Prydain.
- Aelod o Gymdeithas Fycolegol Prydain
Safleoedd academaidd blaenorol
2022 Darlithydd Biocemeg, Prifysgol Caerdydd
2018-2022 Uwch Ymchwilydd Ôl-ddoethurol, Prifysgol Abertawe - ymwrthedd Azole yn Spp Candida.
Swyddog Ymchwil Ôl-ddoethurol 2015 - 2018 , Prifysgol Abertawe - prosiect ERDF - 'BEACON+'
Swyddog Ymchwilydd Ôl-ddoethurol 2010 - 2015 , Prifysgol Abertawe - prosiect ERDF - 'BEACON'
2008 - 2010 Cydymaith Ymchwil Ôl-ddoethurol, Prifysgol Abertawe - BBSRC - ymwrthedd triazole
2005 - 2008 Cydymaith Ymchwil Ôl-ddoethurol, Prifysgol Abertawe - Prosiect FP6 yr UE - 'SterolTalk'
Pwyllgorau ac adolygu
- Golygydd Adolygu, Fungal Pathogenesis;
- Ffiniau mewn Microbioleg Cellog a Heintiedig
- Ffiniau mewn Bioleg Ffwngaidd
- Adolygydd ar gyfer BBSRC a Science Foundation Ireland.
- Adolygydd cymheiriaid ar gyfer gwahanol gyfnodolion.
Meysydd goruchwyliaeth
Goruchwyliaeth gyfredol
Harry Williams
Myfyriwr ymchwil
Contact Details
ParkerJ21@caerdydd.ac.uk
+44 29225 11089
Adeilad Syr Martin Evans, Ystafell W2.39, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX
+44 29225 11089
Adeilad Syr Martin Evans, Ystafell W2.39, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX