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Dr Andrew Warrilow

Dr Andrew Warrilow

Research Officer, Medicine

Telephone number

+44 (0) 1792 295828

Email address

Research Links

Academic Office - 527
Fifth Floor
Institute of Life Science 1
Singleton Campus

About

Dr Andrew Warrilow is a protein biochemist working in the Centre for Cytochrome P450 Biodiversity (http://www.p450swansea.co.uk/) within Swansea University Medical School. He began his career at IACR Long Ashton Research Station near Bristol in 1995 before moving to the Wolfson Laboratory of Cytochrome P450 Biodiversity in Aberystwyth University during 1998 to work with Professor Steven Kelly and subsequently joined Swansea University in 2004.

Andrew's main research interests are sterol 14-alpha demethylases (CYP51) of fungal pathogens and their cytochrome P450 reductase (CPR) redox partners. Fungal CYP51 is the target enzyme of azole antifungal drugs and increasing resistance towards azole antifungals amongst clinical isolates of Candida spp., Aspergillus spp. and Mucorales necessitates greater understanding of azole resistance mechanisms and the synthesis and screening of new therapeutic agents to overcome this growing resistance.

Other research interests include the characterization of eukaryotic and prokaryotic cytochrome P450 monooxygenases, especially in terms of ligand binding, substrate specificity and enzyme kinetics; expertise shared with students enrolled on the taught modules Andrew contributes towards. 

Andrew is a co-investigator on the BEACON (http://www.beaconwales.org) Biorefining Centre of Excellence programme. BEACON is a partnership between Aberystwyth, Bangor and Swansea Universities and the University of South Wales working in the field of conversion of biomass and biowastes into biobased products with commercial applications. BEACON is a £18.3 million project backed by the European Regional Development Fund through the Welsh Government and primarily aims to help Welsh businesses explore biobased opportunities for growth by providing access to wide-ranging specialist equipment and scientific expertise. BEACON won the 2014 RegioStars prize for the best Regional Project in the EU.

 

Areas Of Expertise

  • • Sterol 14-alpha demethylases (CYP51)
  • • NADPH-Cytochrome P450 reductases
  • • Azole antifungal drug screening
  • • Cytochrome P450 monooxygenases
  • • Enzymology
  • • Protein purification
  • • Protein biochemistry

Career Highlights

Research

Resistance to azole antifungal drugs observed in clinical fungal infections amongst Candida spp., Aspergillus spp. and Mucorales is an increasing problem that needs urgent attention.

Andrew has participated in several studies examining the biochemical mode of action of azole antifungals with the target CYP51 enzyme of fungal pathogens and the human homologue. This work has included characterization of the mode of action of new therapeutic agents including the tetrazole VT-1161 (Viamet/Mycovia) and triazole PC945 (Pulmocide). At the time of writing (May 2020) VT-1161 is undergoing Phase 3 trials and PC945 Phase 2 trials.

Other investigations include the underlying biochemical basis for increased azole resistance in Candida albicans and Aspergillus fumigatus clinical isolates previously attributed to amino acid substitutions in the fungal CYP51 enzyme. In C. albicans the effects of individual CYP51 amino acid substitutions on enzyme activity in terms of fluconazole tolerance were additive, whereas in A. fumigatus individual amino acid substitutions in CYP51A can confer significant azole tolerance. In addition the biochemical mode of action for azole antifungals against CYP51 enzymes from Cryptococcus spp., Trichophyton rubrum and Malassezia globosa have also been investigated.

Further understanding the mechanisms involved in CYP51 azole resistance will inform the design of the next generation of therapeutic agents to overcome the emerging resistance to existing azole antifungal drugs.

 

Collaborations

Andrew has several national and international research collaborations coordinated through the Centre for Cytochrome P450 Biodiversity (http://www.p450swansea.co.uk/) within the Medical School.