Antifungal drug discovery, Antifugal resistance, Antifungal mechanism of action
Dr. Bromley spent the majority of his research career working on the mechanistic basis of fungal pathogenicity with the translational emphasis of developing novel antifungal agents. Whilst working for F2G Ltd, a UoM spin-out company, he made a major contribution to the identification of potential drug targets in the pathogenic mould Aspergillus fumigatus and to advancing these discoveries through target validation to drug development.
Dr. Bromley his research team discovered and exploited mobilisable genetic elements in A. fumigatus which facilitated discovery of numerous essential genes. His team has also developed high-throughput gene replacement strategies for A. fumigatus and chemical genetic screens to identify the mechanism of action of antifungal agents.
He worked as a key member of the research team that identified the novel mechanism of action of phase 1 antifungal compound F901318 (F2G Ltd) and he was the co-ordinator of a €6.1M FP7 collaborative research program (NOFUN) taking novel antifungal compounds from hits to clinical trials. His recent research in antifungal resistance has uncovered the mechanistic nature of tandem repeat mediated azole resistance in A. fumigatus.
Gsaller, F., Hortschansky, P., Furukawa, T., Carr, P. D., Rash, B., Capilla, J., Müller, C., Bracher, F., Bowyer, P., Haas, H., Brakhage, A. A. & Bromley, M. J. (2016) Sterol Biosynthesis and Azole Tolerance Is Governed by the Opposing Actions of SrbA and the CCAAT Binding Complex PLoS Pathogens. e1005775.
Carr, P. D., Hey, P., Tuckwell, D. J., D’Enfert, C., Bromley, M. J. (2010) Use of low temperature induced transposition and parasexual genetics to identify essential genes in Aspergillus fumigatus. Eukaryotic Cell 9 438-448.
Oliver, J. D., et al. (2016) F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase. PNAS 113 12809-12814.
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