Conway, Stuart J.

Short Biography

Stuart Conway is the Inaugural holder of the Michael and Alice Jung Endowed Chair of Medicinal Chemistry and Drug Discovery at the University of California, Los Angeles. He studied Chemistry with Medicinal Chemistry at the University of Warwick, completing a final year research project with Dr Andrew Clark (1994-1997). Stuart undertook PhD studies in the Department of Pharmacology at the University of Bristol, with Prof. Jeff Watkins FRS and Prof. David Jane (1997-2000). He then completed post-doctoral studies with Professor Andrew Holmes FRS at the University of Cambridge, and in 2003 he was appointed as a Lecturer in Bioorganic Chemistry at the University of St Andrews. Between 2008 and 2023 Stuart was an Associate Professor, and then Full Professor (2014), at the University of Oxford. Concurrently he was the E. P. Abraham Cephalosporin Fellow in Organic Chemistry at St Hugh’s College, Oxford. Stuart is an Associate Editor for J. Med. Chem. and ACS Bio & Med Chem Au, and is the Immediate Past President of the Royal Society of Chemistry Organic Division.

Research Interests

Conway Group Research Interests

Our research interests are at the interface of chemistry and biology and focus on the use of synthetic organic chemistry to enable the study of biological systems. Much of our current work involves the development of selective molecular probes to enable investigation of certain biological systems. Our research can be grouped into three main areas, (i) investigation of human epigenetic processes in health and disease; (ii) novel probes to measure and target cellular redox; and (iii) the study of parasite epigenetics to target infectious diseases.

Investigation of human epigenetic processes
in health and disease

Epigenetics is the study of heritable changes in gene expression that do not involve changes in DNA sequence, or, how phenotype is linked to genotype. Epigenetic modifications are essential for fundamental biological processes such as cell differentiation to form different tissues like skin, brain, or heart. However, changes in the epigenome can also lead to undesired effects and the cause of diseases including cancer. Histone modifications are key elements of epigenetics. For instance, lysine residues can be methylated or acetylated by ‘writer’ proteins. Epigenetic erasers reverse these processes, and bromodomains are ‘readers’ of acetylated lysine residues. We have developed chemical probes for a number of epigenetic proteins including BRD4 and CREBBP/P300, which are bromodomain-containing proteins. We have used these chemical tools to probe the biological function of these proteins, which has underpinned the development of new therapeutic strategies for cancer.

Probes to measure and target cellular redox

The cellular environment within living systems spans a spectrum of reducing and oxidizing conditions. A balance of cellular redox is important for normal cell function and perturbing this balance can underpin disease states including cancer. We are seeking to develop bio-responsive chemistries that allow in-cell reactions to occur selectively in a given context i.e. oxidizing or reducing conditions. We are applying these chemistries to develop imaging agents that dynamically report on aspects of cellular redox, and pro-drugs that target therapeutic agents to a given cellular environment.

The study of parasite epigenetics
to target infectious diseases

Parasitic species are the causative agents of Chagas disease, leishmaniasis and schistosomiasis, three major neglected tropical diseases that affect millions of people worldwide. The parasites (Trypanosoma, Leishmania and Schistosoma) adopt different forms during their life cycle to adapt to their changing habitats, which include the vector and the host bloodstream. We are investigating the role played by epigenetic processes in phenotypic changes throughout the life cycle of parasites, which are essential for survival and proliferation. Given that bromodomain-containing proteins play a fundamental role in regulating transcription in humans, we hypothesize that they will play equally important roles in parasites. We are investigating whether these proteins are novel therapeutic targets for the treatment of infectious diseases.

Honors & Awards

  • Elected as President of the Royal Society of Chemistry Organic Division (2019-2022).
  • Karle Lecturer at the University of Michigan (2021).
  • Awarded the Biological and Medicinal Chemistry Sector (RSC) Lectureship for 2016.
  • Elected as a Fellow of the Royal Society of Chemistry (FRSC, 2014).
  • Invited to lecture at the Inaugural ACS Division of Medicinal Chemistry Young Investigators’ Symposium, New Orleans (2013).
  • EFMC Prize for a Young Medicinal Chemist in Academia (2012).
  • UK representative at the 4th EuCheMS Young Investigator Workshop in Vienna (2012).
  • Awarded a Junior Scientists Participation Program Fellowship to attend the 47th Bürgenstock conference on Stereochemistry (2012).
  • BP Award for the Best Teacher in Chemistry at the University of St Andrews (2006-2007).
  • Elected to a Research Fellowship at Hughes Hall College, University of Cambridge (2002-2003).

Representative Publications

Below is a list of selected publications:

  • L. D. Wallabregue, H. Bolland, S. Faulkner, E. M. Hammond, S. J. Conway. Two color imaging of different hypoxia levels in cancer cells. J. Am. Chem. Soc., 2023, 145, 2572.
  • R. Sekirnik, J. K. Reynolds, L. See, J. P. Bluck, A. R. Scorah, C. Tallant, B. Lee, K. B. Leszczynska, R. L. Grimley, R. I. Storer, M. Malattia, S. Crespillo, S. Caria, S. Duclos, E. M. Hammond, S. Knapp, G. M. Morris, F. Duarte, P. C. Biggin, S. J. Conway. Identification of histone peptide binding specificity and small molecule ligands for the TRIM33 bromodomain. ACS Chem. Biol., 2022, 17, 2753.
  • S. J. Conway, A. Kawamura, T. M. Marr, F. Platt, A. J. Russell. Increasing Diversity in Admissions to Postgraduate Study. J. Med. Chem., 2022, 65, 5867.
  • M. Brand, J. Clayton, M. Moroglu, M. Schiedel, S. Picaud, J. P. Bluck, A. Skwarska, A. K. N. Chan, C. M. C. Laurin, A. R. Scorah, K. F. L. See, T. P. C. Rooney, O. Fedorov, G. Perell, W. A. Cortopassi, K. E. Christensen, R. I. Cooper, R. S. Paton, W. C. K. Pomerantz, P. C. Biggin, E. M. Hammond, P. Filippakopoulos, S. J. Conway. Controlling intramolecular interactions to develop selective, high-affinity ligands for the CREBBP bromodomain. J. Med. Chem., 2021, 64, 10102.
  • Skwarska, E. D. D. Calder, I. N. Mistry, D. Sneddon, S. J. Conway, E. M. Hammond. Development and pre-clinical testing of a novel hypoxia-activated pan KDAC inhibitor. Cell Chem. Biol., 2021, 28, 1258.
  • N. Favalli, G. Bassi, C. Pellegrino, J. Millul, R. De Luca, S. Cazzamalli, S. Yang, A. Trenner, N. Mozzafari, R. Myburgh, M. Moroglu, S. J. Conway, A. Sartori, M. M. Manz, R. A. Lerner, P. Vogt, J. Scheuermann, D. Neri. Stereo- and regio-defined DNA-encoded chemical libraries enable efficient ligand discovery for conditional CAR-T cell activation and for tumor targeting. Nature Chem., 2021, 13, 540.
  • M. Joffrin, A. M. Saunders, D. Barneda, V. Flemington, A. L. Thompson, H. J. Sanganee, S. J. Conway. Enantioselective synthesis of isotope-enriched phosphatidylinositol-4- and 5-phosphate probes. Chem. Sci., 2021, 12, 2549.
  • M. C. Laurin, J. P. Bluck, A. K. Chan, M. Keller, A. Boczek, L. E. Jennings, A. R. Scorah, K. F. L. See, D. S. Hewings, F. Woodhouse, J. K. Reynolds M. Schiedel, P. G. Humphreys, P. C. Biggin, S. J. Conway. Fragment-based identification of ligands for bromodomain-containing factor 3 of Trypanosoma cruzi. ACS Infect. Dis., 2021, 7, 2238.
  • G. Bassi, N. Favalli, M. Vuk, M. Catalano, A. Martinelli, A. Trenner, A. Porro, S. Yang, C L. Tham, M. Moroglu, W. W. Yue, J. Conway, P. K. Vogt, A. A. Sartori, J. Scheuermann, D. Neri. A single-stranded DNA-encoded chemical library based on a stereoisomeric scaffold enables ligand discovery by modular assembly of building blocks. Advanced Science, 2020, 2001970.
  • Geddes, P. Paramasivan, A. M. Joffrin, K. Grant, A. L. Thompson, K. E. Christensen, S. J. Conway, G. E. D. Oldroyd, P. S. Poole. Engineering transkingdom signalling in plants to control gene expression in bacteria. Nature Commun., 2019, 10, 3430.
  • M. Schiedel, M. Moroglu, D. M. H. Ascough, A. E. R. Chamberlain, J. J. A. G. Kamps, A. R. Sekirnik, S. J. Conway. Chemical epigenetics: the impact of chemical- and chemical biology techniques on bromodomain target validation. Angew. Chem. Int. Ed., 2019, 58, 17930.
  • L. Collins, J. Saha, L. C. Bouchez, E. M. Hammond, S. J. Conway. Hypoxia-activated small molecule-induced gene expression. ACS Chem. Biol., 2018, 13, 3354-3360.
  • M. Schiedel and S. J. Conway. Small molecules as tools to study the chemical epigenetics of lysine acetylation. Curr. Opin. Chem. Biol., 2018, 45, 166.
  • L. J. O’Connor, L. K. Folkes, G. Brown, S. J. Conway, E. M. Hammond. CYP450 Enzymes effect oxygen-dependent reduction of azide-based fluorogenic dyes. ACS Central Science, 2017, 3, 20.
  • K. C. Costa, N. R. Glasser, S. J. Conway, D. K. Newman. Pyocyanin degradation by a novel demethylase impedes Pseudomonas aeruginosa biofilm growth. Science, 2017, 355, 170.
  • R. Sekirnik (née Measures), D. S. Hewings, N. H. Theodoulou, L. Jursins, K. Lewendon, L. E. Jennings, T. P. C. Rooney, T. D. Heightman, S. J. Conway. Isoxazole-derived amino acids are bromodomain-binding acetyl-lysine mimics: incorporation into histone H4 peptides and histone H3. Angew. Chem. Int. Ed., 2016, 55, 8353.
  • L. J. O’Connor, C. Cazares-Körner, J. Saha, C. N. G. Evans, M. R. L. Stratford, E. M. Hammond, S. J. Conway. Design, synthesis and evaluation of molecularly targeted hypoxia-activated prodrugs. Nature Protoc., 2016, 11, 781.
  • M. Brand, A. Measures, B. Wilson, W. A. Cortopassi, R. Alexander, M. Höss, T. P. C. Rooney, D. S. Hewings, R. Paton, S. J. Conway. Small molecule inhibitors of bromodomain-acetyl-lysine interactions. ACS Chem. Biol., 2015, 10, 22.
  • Hay, O. Fedorov, S. Martin, C. Wells, S. Picaud, M. Philpott, O. P. Moteiro, C. M. Rogers, S. J. Conway, T. P. C. Rooney, A. Tumber, C. Yapp, P. Filippakopoulos, M. E. Bunnage, S. Müller, S. Knapp, C. J. Schofield, P. E. Brennan. Discovery and optimization of small molecule ligands for the CBP/p300 bromodomains. J. Am. Chem. Soc., 2014, 136, 9308.
  • T. P. C. Rooney, P. Filippakopoulos, O. Fedorov, S. Picaud, D. A. Hay, S. Martin, A. Tumber, C. M. Rogers, M. Philpott, M. Wang, A. L. Thompson, T. D. Heightman, D. C. Pryde, A. Cook, R. S. Paton, S. Müller, S. Knapp, P. E. Brennan, S. J. Conway. A series of potent CREBBP bromodomain inhibitors reveals an induced fit pocket stabilized by a cation–π interaction. Angew. Chem. Int. Ed., 2014, 53, 6126.
  • Cazares-Körner, I. M. Pires, I. D. Swallow, S. C. Grayer, L O’Connor, M. M. Olcina, M. Christlieb, S. J. Conway, E. M. Hammond. CH-01 is a hypoxia-activated prodrug that sensitizes cells to hypoxia/reoxygenation through inhibition of Chk1 and Aurora A. ACS Chem. Biol., 2013, 8, 1451.
  • S. Hewings, O. Fedorov, P. Filippakopoulos, S. Martin, S. Picaud, A. Tumber, C. Wells, M. M. Olcina, K. Freeman, A. Gill, A. J. Ritchie, D. W. Sheppard, A. J. Russell, E. M. Hammond, S. Knapp, P. E. Brennan, S. J. Conway. Optimization of 3,5-dimethylisoxazole derivatives as potent BET bromodomain ligands. J. Med. Chem., 2013, 56, 3217.
  • S. Hewings, T. P. C. Rooney, L. E. Jennings, D. Hay, C. J. Schofield, P. E. Brennan, S. Knapp, S. J. Conway. Progress in the development and application of small molecule inhibitors of bromodomain-acetyl-lysine interactions. J. Med. Chem., 2012, 55, 9393.
  • M. N. Stanton-Humphreys, R. D. T. Taylor, C. McDougall, M. L. Hart, C. T. A. Brown, N. J. Emptage, S. J. Conway. Wavelength-orthogonal photolysis of neurotransmitters in vitro. Chem. Commun., 2012, 48, 657.
  • S. Hewings, M. Wang, M. Philpott, O. Fedorov, P. Filippakopoulos, S. Picaud, C. Vuppusetty, B. Marsden, S. Knapp, S. J. Conway, T. D. Heightman, 3,5-Dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands. J. Med. Chem., 2011, 54, 6761.