Dr Mikhail Keniya
| Position | Senior Research Fellow |
|---|---|
| Department | Department of Oral Sciences |
| Qualifications | PhD |
| Research summary | Membrane transporters and anti-fungal resistance |
Research
Dr Keniya's main scientific interests are in investigating mechanisms of oral microbial drug resistance, based on his expertise in microbiology, protein chemistry and enzymology, molecular genetics.This includes the structural biology of membrane transporters, and compound library screening. From the beginning of 2011 he has been an associate investigator on a three-year Marsden project Multifunctional azoles: A triple whammy designed to defeat drug resistance awarded to Dr Brian Monk.
Research and collaboration
The goal of the ongoing Marsden project discovery is to design a multifunctional azole antifungal that can also avoid resistance development by inhibiting efflux pumps, which are the major cause of drug resistance in various oral fungi. This is done in collaboration with German pharmaceutical company MicroCombiChem (MCC).This yielded novel efflux pump inhibitors which has generated a new commercial space for MCC.
Publications
Ruma, Y. N., Keniya, M. V., Tyndall, J. D. A., & Monk, B. C. (2022). Characterisation of Candida parapsilosis CYP51 as a drug target using Saccharomyces cerevisiae as host. Journal of Fungi, 8(1), 69. doi: 10.3390/jof8010069
Graham, D. O., Wilson, R. K., Ruma, Y. N., Keniya, M. V., Tyndall, J. D. A., & Monk, B. C. (2021). Structural insights into the azole resistance of the Candida albicans Darlington strain using Saccharomyces cerevisiae lanosterol 14α-demethylase as a surrogate. Journal of Fungi, 7, 897. doi: 10.3390/jof7110897
Monk, B. C., & Keniya, M. V. (2021). Roles for structural biology in the discovery of drugs and agrochemicals targeting sterol 14α-demethylases. Journal of Fungi, 7(2), 67. doi: 10.3390/jof7020067
Monk, B. C., Sagatova, A. A., Hosseini, P., Ruma, Y. N., Wilson, R. K., & Keniya, M. V. (2020). Fungal lanosterol 14α-demethylase: A target for next-generation antifungal design [Invited review]. Biochimica et Biophysica Acta: Proteins & Proteomics, 1868, 140206. doi: 10.1016/j.bbapap.2019.02.008
Keniya, M. V., & Monk, B. C. (2019). Attenuated apoptotic BAX expression as a xenobiotic reporter in Saccharomyces cerevisiae. FEMS Yeast Research, 19(5), foz048. doi: 10.1093/femsyr/foz048
Monk, B. C., & Keniya, M. V. (2017). Using yeast to discover inhibitors of multidrug efflux in Candida albicans. In R. Prasad (Ed.), Candida albicans: Cellular and molecular biology. (2nd ed.) (pp. 491-543). Springer. doi: 10.1007/978-3-319-50409-4
Chapter in Book - Research
Ruma, Y. N., Keniya, M. V., Tyndall, J. D. A., & Monk, B. C. (2022). Characterisation of Candida parapsilosis CYP51 as a drug target using Saccharomyces cerevisiae as host. Journal of Fungi, 8(1), 69. doi: 10.3390/jof8010069
Journal - Research Article
Graham, D. O., Wilson, R. K., Ruma, Y. N., Keniya, M. V., Tyndall, J. D. A., & Monk, B. C. (2021). Structural insights into the azole resistance of the Candida albicans Darlington strain using Saccharomyces cerevisiae lanosterol 14α-demethylase as a surrogate. Journal of Fungi, 7, 897. doi: 10.3390/jof7110897
Journal - Research Article
Keniya, M. V., & Monk, B. C. (2019). Attenuated apoptotic BAX expression as a xenobiotic reporter in Saccharomyces cerevisiae. FEMS Yeast Research, 19(5), foz048. doi: 10.1093/femsyr/foz048
Journal - Research Article
Monk, B. C., Keniya, M. V., Sabherwal, M., Wilson, R. K., Graham, D. O., Hassan, H. F., Chen, D., & Tyndall, J. D. A. (2019). Azole resistance reduces susceptibility to the tetrazole antifungal VT-1161. Antimicrobial Agents & Chemotherapy, 63(1), e02114-18. doi: 10.1128/AAC.02114-18
Journal - Research Article
Keniya, M. V., Ruma, Y. N., Tyndall, J. D. A., & Monk, B. C. (2018). Heterologous expression of full-length lanosterol 14α-demethylases of prominent fungal pathogens Candida albicans and Candida glabrata provides tools for antifungal discovery. Antimicrobial Agents & Chemotherapy, 62(11), e01131-18. doi: 10.1128/aac.01131-18
Journal - Research Article
Keniya, M. V., Sabherwal, M., Wilson, R. K., Woods, M. A., Sagatova, A. A., Tyndall, J. D. A., & Monk, B. C. (2018). Crystal structures of full-length lanosterol 14α-demethylases of prominent fungal pathogens Candida albicans and Candida glabrata provide tools for antifungal discovery. Antimicrobial Agents & Chemotherapy, 62(11), e01134-18. doi: 10.1128/aac.01134-18
Journal - Research Article
Sagatova, A. A., Keniya, M. V., Tyndall, J. D. A., & Monk, B. C. (2018). The impact of homologous resistance mutations from pathogenic yeast on Saccharomyces cerevisiae lanosterol 14α-demethylase. Antimicrobial Agents & Chemotherapy, 62(3), e02242-17. doi: 10.1128/aac.02242-17
Journal - Research Article
Holmes, A. R., Cardno, T. S., Strouse, J. J., Ivnitski-Steele, I., Keniya, M. V., Lackovic, K., Monk, B. C., … Cannon, R. D. (2016). Targeting efflux pumps to overcome antifungal drug resistance. Future Medicinal Chemistry, 8(12), 1485-1501. doi: 10.4155/fmc-2016-0050
Journal - Research Article
Sagatova, A. A., Keniya, M. V., Wilson, R. K., Sabherwal, M., Tyndall, J. D. A., & Monk, B. C. (2016). Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14α-demethylase. Scientific Reports, 6, 26213. doi: 10.1038/srep26213
Journal - Research Article
Tyndall, J. D. A., Sabherwal, M., Sagatova, A. A., Keniya, M. V., Negroni, J., Wilson, R. K., Woods, M. A., … Monk, B. C. (2016). Structural and functional elucidation of yeast lanosterol 14α-demethylase in complex with agrochemical antifungals. PLoS ONE, 11(12), e0167485. doi: 10.1371/journal.pone.0167485
Journal - Research Article
Keniya, M. V., Fleischer, E., Klinger, A., Cannon, R. D., & Monk, B. C. (2015). Inhibitors of the Candida albicans Major Facilitator Superfamily transporter Mdr1p responsible for fluconazole resistance. PLoS ONE, e0126350. doi: 10.1371/journal.pone.0126350
Journal - Research Article
Sagatova, A. A., Keniya, M. V., Wilson, R. K., Monk, B. C., & Tyndall, J. D. A. (2015). Structural insights into binding of the antifungal drug fluconazole to Saccharomyces cerevisiae lanosterol 14α-demethylase. Antimicrobial Agents & Chemotherapy, 59(8), 4982-4989. doi: 10.1128/aac.00925-15
Journal - Research Article
Keniya, M. V., Holmes, A. R., Niimi, M., Lamping, E., Gillet, J.-P., Gottesman, M. M., & Cannon, R. D. (2014). Drug resistance is conferred on the model yeast Saccharomyces cerevisiae by expression of full-length melanoma-associated human ATP-binding cassette transporter ABCB5. Molecular Pharmaceutics, 11(10), 3452-3462. doi: 10.1021/mp500230b
Journal - Research Article
Monk, B. C., Tomasiak, T. M., Keniya, M. V., Huschmann, F. U., Tyndall, J. D. A., O'Connell, III, J. D., Cannon, R. D., … Stroud, R. M. (2014). Architecture of a single membrane spanning cytochrome P450 suggests constraints that orient the catalytic domain relative to a bilayer. PNAS, 111(10), 3865-3870. doi: 10.1073/pnas.1324245111
Journal - Research Article
Keniya, M. V., Cannon, R. D., Nguyễn, Ấ., Tyndall, J. D. A., & Monk, B. C. (2013). Heterologous expression of Candida albicans Pma1p in Saccharomyces cerevisiae. FEMS Yeast Research, 13(3), 302-311. doi: 10.1111/1567-1364.12035
Journal - Research Article
Holmes, A. R., Keniya, M. V., Ivnitski-Steele, I., Monk, B. C., Lamping, E., Sklar, L. A., & Cannon, R. D. (2011). The monoamine oxidase A inhibitor clorgyline is a broad-spectrum inhibitor of fungal ABC and MFS transporter efflux pump activities which reverses the azole resistance of Candida albicans and Candida glabrata clinical isolates. Antimicrobial Agents & Chemotherapy, 56(3), 1508-1515. doi: 10.1128/aac.05706-11
Journal - Research Article
Cannon, R. D., Lamping, E., Holmes, A. R., Niimi, K., Baret, P. V., Keniya, M. V., … Niimi, M., … Monk, B. C. (2009). Efflux-mediated antifungal drug resistance. Clinical Microbiology Reviews, 22(2), 291-321. doi: 10.1128/cmr.00051-08
Journal - Research Article
Holmes, A. R., Lin, Y.-H., Niimi, K., Lamping, E., Keniya, M., Niimi, M., … Monk, B. C., & Cannon, R. D. (2008). ABC transporter Cdr1p contributes more than Cdr2p does to fluconazole efflux in fluconazole-resistant Candida albicans clinical isolates. Antimicrobial Agents & Chemotherapy, 52(11), 3851-3862. doi: 10.1128/AAC.00463-08
Journal - Research Article
Monk, B. C., & Keniya, M. V. (2021). Roles for structural biology in the discovery of drugs and agrochemicals targeting sterol 14α-demethylases. Journal of Fungi, 7(2), 67. doi: 10.3390/jof7020067
Journal - Research Other
Monk, B. C., Sagatova, A. A., Hosseini, P., Ruma, Y. N., Wilson, R. K., & Keniya, M. V. (2020). Fungal lanosterol 14α-demethylase: A target for next-generation antifungal design [Invited review]. Biochimica et Biophysica Acta: Proteins & Proteomics, 1868, 140206. doi: 10.1016/j.bbapap.2019.02.008
Journal - Research Other
