Dr Paul Clarke is a Team Leader working in the Centre for Cancer Drug Discovery at The Institute of Cancer Research (ICR). He is a highly experienced molecular and cell biologist with expertise in the analysis of RNA:protein interactions and the regulation of gene expression. He has many years’ experience of collaborative project-based drug discovery, including serving on steering committees with commercial partners.
Dr Clarke enjoys the multidisciplinary nature of drug discovery projects and working on projects with team members from different scientific backgrounds and academic or commercial organisations. He especially appreciates the intellectual challenge of both cancer target discovery, validation and drug discovery, particularly for targets that that require innovative thinking or the identification or application of novel technologies or strategies to answer challenging questions.
Prior to joining ICR, Dr Clarke trained as a molecular biologist exploring the regulation of protein synthesis by RNA-binding proteins in cells transformed by DNA tumour viruses. Initially at University of London and then winning a prestigious Human Frontiers Science Program Fellowship to continue his training at Cold Spring Harbor Laboratories in New York.
On joining the ICR, Dr Clarke’s research focused on the molecular pharmacology of novel inhibitors of signal transduction in cancer, particularly on the discovery and development of HSP90 and PI3 kinase inhibitors. Dr Clarke’s research has contributed to the discovery of the structure and function of a key cancer molecule, HSP90, and drugs which target this protein.
The significance of this pioneering research was recognised by the award of the prestigious Cancer Research UK Translational Cancer Research Prize (2013) and Dr Clarke was a member of this team of senior scientists. As a member of a multidisciplinary team Dr Clarke led the molecular pharmacology and mechanism of action studies that contributed to the development of HSP90 (luminespib; AUY922) and PI3K (pictilisib; GDC-0941) inhibitors that progressed to clinical trials worldwide.
More recently, he has jointly led the team that discovered NXP800, an inhibitor of HSF1 activation that entered clinical studies in early 2022. Dr Clarke also led the biology for a collaborative ICR/Merck KGaA WNT pathway project team that discovered potent and selective inhibitors of the mediator complex associated protein kinases, CDK8/19, using phenotypic screening and chemo-proteomics.
Dr Clarke currently leads and focuses on the mechanisms of molecular cancer therapies and particularly targeting the addiction or dependency of cancer cells on RNA binding proteins or their complexes. This includes drug discovery projects developing selective inhibitors of pre-mRNA splicing.
Overall, Dr Clarke aims to contribute to the wider goal of the ICR Centre for Cancer Drug Discovery to improve the lives of cancer patients through the discovery and development of personalised molecular medicines and is a keen supporter and contributor to the CTU’s early-stage target evaluation and validation groups.