Prof. Susan Wyllie

Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee “The direct approach: the role of chemical proteomics in drug target deconvolution”

Work address                  Wellcome Centre for Anti-Infectives Research, School of Life Sciences,                                               Wellcome Trust Building, University of Dundee, DD1 5EH
Web page                         www.modeofactiondundee.org
University Education
1991-1995BSc (Hons) Biochemistry (2nd Class, Division I) Degree, University of Edinburgh
1995-1998Ph.D., University of Edinburgh
Employment History
1999-2000Postdoctoral Research Fellow – Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.
2000-2001Research Assistant Professor – Departments of Microbiology and Pathology, J. H. Quillen College of Medicine, Johnson City, TN, USA.
2001-2016Senior Research Associate and Part-time Lecturer Division of Biological Chemistry and Drug Discovery, University of Dundee, Scotland.
2015-2017Mode of Action Group (Team Leader) – Division of Biological Chemistry and Drug Discovery, University of Dundee, Scotland.
2017-2019Independent Investigator (Mode of Action Group) – Wellcome Centre for Anti-Infectives Research, University of Dundee, Scotland.
2019-present   2023-present   2024-presentPrinciple Investigator (Mode of Action Group) – Wellcome Centre for Anti-Infectives Research (WCAIR), University of Dundee, Scotland. Deputy Head of Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Scotland. Professor of Biochemical Pharmacology, University of Dundee
Honours and Awards
1998UK Chlamydia Research Award (sponsored by Behring)
2007The National Centre for the Replacement, Refinement and Reduction of Animals in Research prize for published work that advances, or has the potential to advance, knowledge in the 3Rs
2017     2023   2023     2023     2024GlaxoSmithKline’s Annual Scientific Termination of Projects (STOP) Award. Awarded for “Impact and value of science-led decisions in allowing reinvestment of valuable resources into transformative medicines” CA Wright Memorial Medal (2023) – Awarded by the British Society of Parasitology in recognition of outstanding contribution to the discipline of parasitology. School of Life Sciences Innovators of the Year (2022) – Team: Simone Altmann, Sandra Carvalho, Melanie Ridgway, Anna Trenaman, Michele Tinti, and David Horn. Oligo targeting for profiling drug resistance mutations in the parasitic trypanosomatids Biochemical Society – Industry and Academic Collaboration Award in recognition of GSK /University of Dundee world-leading work to develop new medicines for Neglected Tropical Diseases Drugs for Neglected Diseases Initiative – Project of the Year. Part of team responsible for delivery of DNDI-6899 to phase I clinical trials for the treatment of visceral leishmaniasis
                                       Professional service
Executive council member – Malaria Drug Accelerator Board member – Wellcome Centre for Anti-Infectives Research Editorial board member – PLOS Pathogens Grant reviewer and panel member – European Society of Clinical Microbiology and Infectious Diseases and European Society of Clinical Microbiology and Infectious Diseases Member of the Drugs for Neglected Diseases Initiative (DNDi) Mode of Action consortium and Wellcome’s HIT-NTD consortium
Active awards
Gates Foundation2023-26£3.9MMale contraceptive drug development using a novel human sperm phenotype. (Co-I).
Gates Foundation Gates Foundation2022-25 2022-25£1.3M $1.5MAntimalarial Mode of Action Studies (Co-PI) Fully functional chemical probe library and proteomic POC enablement (PI)
Wellcome Trust   Wellcome Trust2022-25   2021-24£246,000   £4.9MApplication of biotransformations to neglected tropical disease research (Co-PI) A platform for drug target deconvolution and exploitation (PI)
Wellcome Trust2022-24£5.2MWellcome Centre for Anti-Infectives Research – Innovations Extension (Co-I).
Wellcome Trust2022-26£4.5MDevelopment of a new preclinical candidate for Chagas disease (Co-I)
     

Selected publications (H-index 41, >5400 citations)

  1. Wall, R J. ResMAP- a saturation mutagenesis platform enabling parallel profiling of target-specific resistance-conferring mutations in Plasmodium. 15: e0170824.
  2. Tulloch, L. B. et al. (2024) Sterol 14-alpha demethylase (CYP51) activity in Leishmania donovani is likely dependent upon cytochrome P450 reductase 1. PLOS Pathog. 20: e1012382.
  3. Braillard, S. et al. (2023) DNDI-6174, a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc1 complex. Sci. Trans. Med. 15: eadh9902.
  4. González, S. et al. (2023) Short-course combination treatment for experimental chronic Chagas disease. Sci. Trans. Med. 15: eadg8105.
  5. Hanna, J. et al. (2023) Mode of action studies confirm on-target engagement of lysyl-tRNA synthetase inhibitor and lead to new selection marker for Cryptosporidium. Front. Cell. Infect. Microbiol. 13: 1236814.
  6. Cleghorn, L. A. T. et al. (2023) Development of a 2,4-Diaminothiazole series for the treatment of Human African Trypanosomiasis highlights the importance of static-cidal screening of analogues. J. Med. Chem. 66: 8896-8916.
  7. Bopp, S. et al (2023) Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation. Nat Comm. 14:1455.
  8. Smith, RJ. et al. (2023) Chemical pulldown combined with mass spectrometry to identify the molecular targets of antimalarials in cell-free lysates. STAR Protoc. 4: 102002.
  9. Benns, HJ. et al. (2022) CRISPR-based oligo recombineering prioritizes apicomplexan cysteines for drug discovery. Nat Microbiol. 7:1891-1905.
  10. Milne, R. et al. (2022) Toolkit of approaches to support target-focused drug discovery for Plasmodium falciparum lysyl tRNA synthetase. ACS Infect Dis. 8:1962-1974.
  11. De Rycker et al. (2022) Anti-trypanosomatid drug discovery: progress and challenges. Nat Rev Microbiol. 22;1-16. (Review)
  12. Tamaki, F. et al. (2022) High-throughput screening platform to identify inhibitors of protein synthesis with potential for the treatment of malaria. Antimicrob Agents Chemother. 66:e0023722.
  13. Altmann, S. et al. (2022) Oligo targeting for profiling drug resistance mutations in the parasitic trypanosomatids. Nucleic Acids Res. 50: e79.
  14. Smith, A. et al. (2022) Repositioning of a diaminothiazole series confirmed to target the cyclin-dependent kinase CRK12 for use in the treatment of African animal trypanosomiasis. J. Med Chem 65: 5606-5624.
  15. Lima, M. et al. (2022) Identification of a proteasome-targeting arylsulfonamide with potential for the treatment 1 of Chagas’ disease. Antimicrob Agents Chemother 66: e0153521.
  16. Mowbray et al. (2021) DNDI-6148: A novel benzoxaborole preclinical candidate for the treatment of visceral leishmaniasis. J. Med Chem 64, 16159-16176.
  17. Corpas-Lopez, V. and Wyllie, S. Utilizing thermal proteome profiling to identify the molecular targets of anti-leishmanial compounds. STAR Protoc. 2, 100704.
  18. Paradela, L. et al. (2021) Multiple unbiased approaches identify oxidosqualene cyclase as the molecular target of a promising anti-leishmanial. Cell Chem. Biol. 28, 711-721.
  19. Wall, R.J et al. (2020)The Qi site of cytochrome b is a promiscuous drug target in Trypanosoma cruzi and Leishmania donovani. ACS Infect Dis. 6: 515-528.
  20. Wyllie, S et al. (2019) Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition. PNAS. 116: 9318-9323.
  21. Corpas-Lopez, V. et al. (2019) Pharmacological validation of N-myristoyltransferase as a drug target in Leishmania donovani. ACS Infect Dis. 5: 111–122.
  22. Wyllie, S.et al. (2018) Cyclin-dependent kinase 12, a novel drug target for visceral leishmaniasis. Nature 560:192-197.
  23. Wall, R. J. et al. (2018) Anti-trypanosomal 8-hydroxy naphthyridines are chelators of divalent transition metals. Antimicrob Agents Chemother. 62. pii: e00235-18.

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