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Health Sciences profile

Dr Mikhail Keniya

PositionSenior Research Fellow
DepartmentDepartment of Oral Sciences
QualificationsPhD
Research summaryMembrane 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

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