Professor Liam Cox BA (hons) (Cantab), PhD (Cantab)

Professor Liam Cox

School of Chemistry
Director of Research and Knowledge Transfer
Professor in Biological Organic Chemistry

Contact details

Address
School of Chemistry
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Liam Cox is Professor Reader in Biological Organic Chemistry at The University of Birmingham and heads up the School’s Chemical Biology and Drug Discovery Research Theme. 

Since joining Birmingham in 1999, he has supervised over 20 PhD students, published extensively in the scientific literature and secured funding from the EPSRC and MRC, EU, Wellcome Trust, The Leverhulme Trust and the Pharmaceutical Industry.  His research interests are currently focused around the development of new synthetic methods and the application of molecular synthesis to chemical biology and drug discovery.

He recently led a €1.6M EU-funded European Industrial Doctorate Innovative Training Network, iDESIGN, whose primary focus is to deliver better starting points for drug discovery.

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Qualifications

  • Postgraduate Certificate in Learning and Teaching in Higher Education (2002)
  • PhD in Organic Chemistry, University of Cambridge (1998)
  • BA (Hons) in Natural Sciences, University of Cambridge (1994)
  • Member of the Royal Society of Chemistry (2003-present)

Biography

Liam Cox graduated in 1994 from the University of Cambridge (King’s College) with a BA (hons) Class I degree in Natural Sciences, specialising in Chemistry. He remained in Cambridge to carry out his PhD, working under the supervision of Professor Steven Ley FRS CBE on the use of π-allyltricarbonyliron lactone complexes in remote asymmetric induction. 

On completing his PhD in 1997, he moved to the ETH-Zürich to work as a post-doctoral research fellow in the group of Professor François Diederich where he developed synthetic approaches to chiral 1,3-diethynylallenes and investigated their use as highly unsaturated monomers for the preparation of helical polymers.

In September 1999, he took up an Academic position at the University of Birmingham where he is currently Professor in Biological Organic Chemistry.

Teaching

Dr Cox has taught a wide range of courses spanning core Organic Chemistry and Biological Organic Chemistry. 

  • Level 1 courses: Carbonyl Chemistry; Nucleophilic Substitution and Elimination; Structure Elucidation
  • Level 2 courses: Aromatic Chemistry; Enolates; Retrosynthesis 
  • Level 3 courses: Conformational Analysis; Applications of Main Group Elements in Synthesis; Asymmetric Catalysis
  • Level 4 courses: Natural Product Synthesis; Biological Carbohydrate Chemistry; Modern Synthetic Methods

Postgraduate supervision

Research projects in the Cox group provide excellent training for anyone wishing to pursue a career in synthetic organic chemistry or chemical biology. 

Potential applicants interested in joining the group are encouraged to contact Professor Cox directly by email.

Research

RESEARCH THEMES AND ACTIVITY

Organic Chemistry focusing on Stereoselective Synthesis and Asymmetric Catalysis
The Cox group has a long-standing interest in stereoselective synthesis and in particular, the allylation reaction, which is one of the most valuable C-C bond-forming processes available to the synthetic chemist. We have shown how employing a temporary silicon connection to tether two reacting moieties can dramatically improve / reverse the stereoselectivity of a subsequent intramolecular allylation [Beignet, J., Jervis, P. J., Cox, L. R., (2008), Temporary Silicon Connection Strategies in Intramolecular Allylation of Aldehydes using Allylsilanes. J. Org. Chem., 73: 5462-5475.].

We have also developed intramolecular allylation strategies to synthesise a range of oxygen heterocycles and recently employed our methodology in the first total synthesis of the natural product (-)-aureonitol [Jervis, P. J., Cox, L. R., (2008), Total synthesis of (-)-Aureonitol and 3-epi-Aureonitol. Confirmation of Relative Stereochemistry. J. Org. Chem., 73: 7616-7624.].

Research has more recently shifted away from substrate-controlled reactions to reagent-controlled processes, with a particular focus on the use of chiral Brønsted acids and chiral anions as organocatalysts for the enantioselective allylation of latent electrophiles.

Carbohydrate Chemistry and Chemical Biology
Carbohydrate chemistry has been a research interest in the group for some time. In recent years, we have begun to employ our synthesis skills in the glycolipid arena as part of a highly multidisciplinary project in association with Prof Del Besra (Microbiology, Birmingham) and Prof Vincenzo Cerundolo (Immunology, Oxford).  

This productive interdisciplinary research programme focuses on the CD1d molecule, which is a protein that binds glycolipids. Recognition of the resulting protein-lipid complex by receptors on invariant Natural Killer T cells results in an immune response. 

We have synthesised a diverse range of novel glycolipids and shown that the structure of the bound glycolipid determines whether the immune response is activated or suppressed. This opens up the possibility of using these small-molecule regulators of the immune response to treat a range of diseases [Jervis, P. J., Cox, L. R., Besra, G. S. (2011) Synthesis of a Versatile Building Block for the Preparation of 6-N-Derivatized α-Galactosyl Ceramides: Rapid Access to Biologically Active Glycolipids. J. Org. Chem., 76: 320-323.]. 

We are also using labelled analogues to help shed more insight into the mode of action of different glycolipids CD1d agonists [Garcia-Diaz, Y. R., Wojno, J., Cox, L. R., Besra, G. S., (2009), Synthesis of Threitol Ceramide and [14C]Threitol Ceramide, Non-Glycosidic Analogues of the Potent CD1d Antigen α-Galactosyl Ceramide. Tetrahedron: Asymmetry, 20: 747-753.].

Oligoynes and related π-Conjugated Molecules
We have developed a conceptually new approach to oligoyne assembly [for a review: Weller, M. D., Cox, L. R., (2009), A Novel Twist on an Old Theme: β-Halovinylsilanes, A New Elimination Approach to Oligoyne Assembly. C. R. Chimie, 12: 366-377.], which has culminated in our report of the synthesis of a dodecayne [Simpkins, S. M. E., Weller, M. D., Cox, L. R., (2007), β-Chlorovinylsilanes as Masked Alkynes in Oligoyne Assembly: Synthesis of the First Aryl-End-Capped Dodecayne. Chem. Commun., 4035-4037.] This polyyne, consisting of 24 linearly arranged carbon atoms, represents the longest aryl end-capped oligoyne reported to-date and indeed one of the longest oligoynes ever reported. Oligoyne encapsulation strategies are also being developed in order to access even longer π-conjugated frameworks [Simpkins, S. M. E., Kariuki, B. M., Cox, L. R., (2006), Towards the Synthesis of Insulated Oligoynes: a Ring-Closing-Metathesis Approach to Molecular Encapsulation. J. Organomet. Chem., 691:5517-5523.].

Other activities

  • Society of Chemical Industry:
    • 2003–2008: Invited member and Chair (2006­–2008) of Young Chemists’ Panel.
    • 2009–present: Invited member of Fine Chemicals Group; Treasurer (2013–2015), Secretary (2015–2017) and Chair (2017–2019).

Publications

Recent publications

Article

Murray, AJ, Cox, LR, Adcock, HV & Roberts, RA 2024, 'Academic drug discovery: Challenges and opportunities', Drug Discovery Today, vol. 29, no. 4, 103918. https://doi.org/10.1016/j.drudis.2024.103918

Frommer, J, Oppenheimer, R, Allott, BM, Núñez‐Pertíñez, S, Wilks, TR, Cox, LR, Bath, J, O'Reilly, RK & Turberfield, AJ 2024, 'A New Architecture for DNA‐Templated Synthesis in Which Abasic Sites Protect Reactants from Degradation', Angewandte Chemie (International Edition) . https://doi.org/10.1002/anie.202317482

Frommer, J, Oppenheimer, R, Allott, BM, Núñez‐Pertíñez, S, Wilks, TR, Cox, LR, Bath, J, O'Reilly, RK & Turberfield, AJ 2024, 'A New Architecture for DNA‐Templated Synthesis in Which Abasic Sites Protect Reactants from Degradation', Angewandte Chemie. https://doi.org/10.1002/ange.202317482

Cao, T-P, Shahine, A, Cox, LR, Besra, GS, Moody, DB & Rossjohn, J 2024, 'A structural perspective of how T cell receptors recognise the CD1 family of lipid antigen-presenting molecules', Journal of Biological Chemistry. https://doi.org/10.1016/j.jbc.2024.107511

Cui, Y, Lanne, A, Peng, X, Browne, E, Bhatt, A, Coltman, NJ, Craven, P, Cox, LR, Cundy, NJ, Dale, K, Feula, A, Frampton, J, Fung, M, Morton, M, Goff, A, Salih, M, Lang, X, Li, X, Moon, C, Pascoe, J, Portman, V, Press, C, Schulz-Utermoehl, T, Lee, S, Tortorella, MD, Tu, Z, Underwood, ZE, Wang, C, Yoshizawa, A, Zhang, T, Waddell, SJ, Bacon, J, Alderwick, L, Fossey, JS & Neagoie, C 2024, 'Azetidines Kill Multidrug-Resistant Mycobacterium tuberculosis without Detectable Resistance by Blocking Mycolate Assembly', Journal of Medicinal Chemistry, vol. 67, no. 4, pp. 2529-2548. https://doi.org/10.1021/acs.jmedchem.3c01643

Batt, SM, Toth, S, Rodriguez, B, Abrahams, KA, Veerapen, N, Chiodarelli, G, Cox, LR, Moynihan, PJ, Lelievre, J, Fütterer, K & Besra, GS 2023, 'Assay development and inhibition of the Mt-DprE2 essential reductase from Mycobacterium tuberculosis', Microbiology, vol. 169, no. 1, 001288. https://doi.org/10.1099/mic.0.001288

Martin, A, Jemmett, P, Howitt, T, Wood, M, Burley, A, Cox, L, Dafforn, T, Welbourn, R, Campana, M, Skoda, MWA, Thompson, J, Hussain, H, Rawle, JL, Carla, F, Nicklin, CL, Arnold, T & Horswell, SL 2023, 'Effect of anionic lipids on mammalian plasma cell membrane properties', Langmuir, vol. 39, no. 7, pp. 2676-2691. https://doi.org/10.1021/acs.langmuir.2c03161

Moetazedian, A, Candeo, A, Liu, S, Hughes, A, Nasrollahi, V, Saadat, M, Bassi, A, Grover, LM, Cox, LR & Poologasundarampillai, G 2023, 'Versatile Microfluidics for Biofabrication Platforms Enabled by an Agile and Inexpensive Fabrication Pipeline', Advanced Healthcare Materials. https://doi.org/10.1002/adhm.202300636

Jemmett, PN, Milan, DC, Nichols, RJ, Howitt, T, Martin, A, Arnold, T, Rawle, JL, Nicklin, CL, Dafforn, TR, Cox, LR & Horswell, SL 2022, 'Influence of the lipid backbone on electrochemical phase behavior', Langmuir, vol. 38, no. 46, pp. 14290-14301. https://doi.org/10.1021/acs.langmuir.2c02370

Jemmett, P, Milan, DC, Nichols, RJ, Cox, L & Horswell, SL 2021, 'Effect of molecule structure on electrochemical phase behavior of phospholipid bilayers on Au(111)', Langmuir, vol. 37, no. 40, pp. 11887-11899. https://doi.org/10.1021/acs.langmuir.1c01975

Kharkwal, SS, Johndrow, CT, Veerapen, N, Kharkwal, H, Saavedra-Avila, NA, Carreño, LJ, Rothberg, S, Zhang, J, Garforth, SJ, Jervis, PJ, Zhang, L, Donda, A, Besra, AK, Cox, LR, Almo, SC, Howell, A, Evans, EE, Zauderer, M, Besra, GS & Porcelli, SA 2021, 'Serial stimulation of invariant natural killer T cells with covalently stabilized bispecific T cell engagers generates anti-tumor immunity while avoiding anergy', Cancer Research, vol. 81, no. 7, pp. 1788-1801. https://doi.org/10.1158/0008-5472.CAN-20-2219

Abstract

Read, M, Zha, L, Brookes, K, Kim, J, Small, B, Kocbiyik, M, Manivannan, S, Bottegoni, G, Cox, L, Kannappan, V, Wang, W, Sunassee, K, Blower, P, Nieto, H, Smith, V & McCabe, C 2023, 'Rational drug design of VCP inhibitors to enhance nis function in radioiodide therapy', Thyroid, vol. 33, no. S1, Oral 8, pp. A4-A4. https://doi.org/10.1089/thy.2023.29156.abstracts

Zha, L, Brookes, K, Kim, J, Small, B, Kocbiyik, M, Manivannan, S, Nieto, H, Bottegoni, G, Cox, L, Kannappan, V, Wang, W, Sunassee, K, Blower, P, Smith, V, Read, M & McCabe, C 2023, 'Rational drug design of VCP inhibitors to enhance NIS function in radioiodide therapy', Thyroid Research, vol. 16, no. S1, OR3, pp. 4-4. https://doi.org/10.1186/s13044-023-00170-8

Preprint

Brookes, K, Thornton, CEM, Zha, L, Kim, J, Small, B, Fear, JS, Nieto, HR, Western, H, Jones, A, Pham, TT, Bottegoni, G, Cox, LR, Kannappan, V, Wang, W, Gorvin, CM, Stover, DG, Spitzweg, C, Jhiang, S, Ringel, MD, Campbell, MJ, Sunassee, K, Blower, PJ, Boelaert, K, Smith, VE, Read, ML & McCabe, CJ 2024 'Clinical Implications of Dually Targeting the Sodium Iodide Symporter in Canonical and Non-Canonical Settings' SSRN. <https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4996070>

Review article

Lewns, FK, Tsigkou, O, Cox, LR, Wildman, RD, Grover, LM & Poologasundarampillai, G 2023, 'Hydrogels and Bioprinting in Bone Tissue Engineering: Creating Artificial Stem-Cell Niches for In Vitro Models', Advanced Materials. https://doi.org/10.1002/adma.202301670

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