Enabling Protein Degradation Drug Discovery

Professor Sir Philip Cohen FRS FRSE, Chairman of the Scientific Advisory Board

Philip Cohen received his BSc (1966) and PhD (1969) from University College London and then spent two years as a postdoctoral fellow at the University of Washington, Seattle, USA with Edmond Fischer (the 1992 Nobel Laureate for Medicine or Physiology).  In 1971 he returned to the UK to become a Faculty member at the University of Dundee, Scotland where he has worked ever since.  Philip was a Royal Society Research Professor from 1984 to 2010, Director of the Medical Research Council Protein Phosphorylation Unit from 1990 to 2012 and Director of the Scottish Institute for Cell Signalling (focussed on ubiquitylation research) from 2008 to 2012.  Philip was the Co-Director of the Division of Signal Transduction Therapy, Europe’s largest collaboration between a basic research institution and the pharmaceutical industry from 1998 to 2012 and is Deputy Director from 2012 to 2016.  The DSST is widely regarded as a model for productive interaction between industry and academia, for which it received a Queen’s Anniversary Award for Higher Education in 2006.

For the past 40 years, Philip’s research has been devoted to studying the role of protein phosphorylation in cell regulation and human disease, a process that controls almost all aspects of cell life.  His contributions to this topic include working out the signalling pathway downstream of PI 3-kinase by which insulin stimulates glycogen synthesis in muscle, the classification and characterization of serine/threonine-specific protein phosphatases and the elucidation of MAP kinase cascades.  Currently his laboratory is trying to unravel the signalling networks in the innate immune system that control the production of pro-inflammatory cytokines and interferons during bacterial and viral infection, and in which the interplay between protein ubiquitylation and protein phosphorylation plays a critical role.  According to Thomson Scientific, Philadelphia, Philip Cohen was the world’s second most cited scientist in the field of biology and biochemistry from 1992-2003, and the most cited biochemist from 1999-2009.

Professor Dario Alessi FRS FRSE

Dario Alessi was born in France, attended high school in Brussels and obtained a BSc in Biochemistry from the University of Birmingham, UK in 1988. He received his PhD in 1991 for work on the synthesis and use of spin-labelled ATP analogues to study muscle contraction under the joint supervision of Ian Trayer (University of Birmingham) and David Trentham FRS (National Institute of Medical Research, Mill Hill, London). He then carried out postdoctoral research with Sir Philip Cohen FRS in the MRC Protein Phosphorylation Unit at Dundee from 1991 to 1997, where he became fascinated by protein kinases and how they are regulated by insulin, growth factors and other extracellular signals that control almost all aspects of cell biology.

In 1998 Dario became a Programme Leader in the MRC Protein Phosphorylation Unit, and assumed the Directorship of the combined Protein Phosphorylation and Ubiquitylation Unit in April 2012. A key focus of his current research is to understand the regulation and physiological roles of poorly understood protein kinases and regulators of the ubiquitylation system that are implicated in human disease. Dario is very keen to exploit findings emerging from his studies to develop novel treatments for disease.

Professor Ron Hay FRS FRSE

Ron Hay was born and educated in Dundee and obtained his BSc in Biochemistry at Heriot-Watt University, Edinburgh in 1975. He obtained his PhD in 1979 from the Medical Research Council Virology Unit in Glasgow under the supervision of Dr John Hay for studies on the replication of herpes simplex virus DNA. A Damon Runyon-Walter Winchell Cancer Fund post doctoral fellowship award led him to work in the laboratory of Dr Mel DePamphilis at Harvard Medical School, Boston where he determined the location and structure of RNA primers that initiate DNA replication at the Simian Virus 40 origin of replication. Returning to the MRC Virology Unit in 1982, he established an independent laboratory working on the initiation of adenovirus DNA replication. In 1985 he moved to the University of St. Andrews where he held Lecturer and Reader positions before taking up the Chair in Molecular Biology and becoming Deputy Director of the new Centre for Biomolecular Sciences. In 2005 he joined the Wellcome Trust Centre for Gene Regulation and Expression in the College of Life Sciences at the University of Dundee as Professor of Molecular Biology.

Ron’s research has established conjugation with the Small Ubiquitin-like Modifier (SUMO) as an important regulatory mechanism in eukaryotes. He recently uncovered a key role for SUMO and ubiquitin in mediating the therapeutic effects of arsenic for the treatment of Acute Promyelocytic Leukaemia.

Dr John Harris CChem FRSC

John Harris graduated from Exeter University in 1969. After gaining a PhD at Queen Mary College (University of London) he spent two years at Liverpool with Charles Rees FRS then joined the Wellcome Foundation, initially  working with Sir John Vane’s group on the discovery of prostacyclin and novel prostanoid drugs. Later, he joined Sir James Black’s analytical pharmacology team, work which led to a number of pre-clinical candidates, culminating in the invention of the 5HT1b/d agonist, ZomigTM, the second major prescription antimigraine drug that was developed latterly by AstraZeneca as a consequence of the Glaxo acquisition of Wellcome at that time. He was appointed Head of Wellcome’s UK cardiovascular therapeutic area, during which time he became interested in the then new field of kinase inhibitors. After the acquisition of Wellcome by Glaxo, he decided to leave GW and, together with some key colleagues, he founded BioFocus, a highly successful early-stage CRO, now part of the Charles River organization. As pharmaceutical interest in kinase inhibitors took off, he initiated the development of small highly-designed focused libraries for screening, leading to many patents in the kinase area for clients and commercial success for BioFocus, and he subsequently developed the focused library concept into other fields, including anti-infectives and ion channel modulators, from which other clinical candidates, notably against malaria, have emerged. John retired from BioFocus after the successful friendly merger with Galapagos NV, who have since taken a number of BioFocus-originated compounds to the clinic. He now runs a small pharma/biotech consultancy, having worked with a diversity of clients, including several start-ups, as well as commercial pharma, UK and US universities, and institutions including the Bill and Melinda Gates Foundation, the Max Planck Institute and the Wellcome Trust. His main current scientific interests are in the field of multi-targeted drugs and, on the more strategic side, the changing structure of drug research and associated business models. He has edited books on both these topics, alongside over 100 scientific papers and patents published over the years. Having consulted for many international clients, and in addition to his work on the Ubiquigent SAB, presently he is working on tuberculosis therapeutics with the University of Cape Town, he sits on the South African Medical Research Council SAB and on the Steering Group of the Wellcome Trust – funded CAMSEED project targeted at kinases involved in resistant breast cancer. He is a chartered chemist and was elected a Fellow of the RSC in 2005.

Professor Helen Walden

Helen is Professor of Structural Biology at the University of Glasgow and Director of the Institute of Molecular Cell and Systems Biology, with over 20 years’ experience in the UPS. Her team recently reported the structure of USP1 in complex with a USP1 inhibitor. The first DUB inhibitor to enter clinical development was developed by KSQ Therapeutics against this target. Helen previously worked at the MRC-Phosphorylation and Ubiquitylation Unit at the University of Dundee after establishing her own group at Cancer Research UK’s London Research Institute, now the Francis Crick Institute. She completed her postdoctoral research at St Jude’s Children’s Research Hospital in Memphis, Tennessee, where she focused on the mechanisms of ubiquitination and solved the structure of the E1 enzyme for Nedd8. Helen holds a BSc in Biochemistry from the University of Bath and a PhD from the University of St Andrews, investigating the structural basis of protein hyperthermostability.

Professor John Davis

John is Chief Scientific Officer for the Centre for Medicines Discovery at the University of Oxford and Director of Business Development for the Alzheimer’s Research UK (ARUK) Drug Discovery Alliance. He has more than 25 years of drug discovery expertise, having progressed multiple drug candidates into the clinic. John first joined the University of Oxford to set up and lead the ARUK Oxford Drug Discovery Institute and during his tenure has formed several industrial alliances. As Head of Biology at GlaxoSmithKline, John led pre-clinical pharmacology research departments prior to co-founding Convergence Therapeutics, subsequently acquired by Biogen, as well as a further three start-up companies. He received his BSc in Biochemistry from the University of Bristol and a PhD in the molecular pathology of cardiovascular disease from the University of Cambridge, with postdoctoral training at the Ludwig Institute and an EMBO fellowship at The Salk Institute.