Professor John Atack
Director, Medicines Discovery Institute
I am a molecular pharmacologist with over 25 years of drug discovery experience, primarily in the field of neuroscience. During this time, I have contributed to the earliest stages of drug discovery (target identification and target validation) all the way through to Phase 1 and Phase 2 clinical trials.
I have worked on a number of different types of drug targets (enzymes, G-protein-coupled receptors and ion channels) covering a range of neurodegenerative diseases (e.g. Alzheimer’s, Huntington’s and Parkinson’s diseases) and psychiatric disorders (bipolar disorder, schizophrenia, generalised anxiety disorder, depression). I am particularly interested in the translational aspects of preclinical drug discovery which give confidence that a particular drug candidate can engage with the target and produce a functional readout in man.
My favourite drug and mechanism of action? Well, that would have to be diazepam and the GABAA receptor ... Or maybe it is ketamine and the NMDA receptor … Or lithium and however that works in bipolar disorder … Not to mention donepezil, so I won’t.
Following a PhD in neurochemical pathology in the Department of Pathology in Newcastle General Hospital, I worked for 5 years (1984-89) in the Laboratory of Neuroscience in the National Institute on Aging on the National Institutes of Health (NIH) campus in Bethesda, Maryland, studying pre- and post-mortem changes in the neurochemistry of patients with Alzheimer’s disease and Down syndrome.
During my time at the NIH, I started a project looking at developing inhibitors of acetylcholinesterase for the treatment of Alzheimer’s disease. From there, I joined the Merck Sharp and Dohme Neuroscience Research Centre in Harlow where I worked from 1989-2006 on a variety of in vitro and in vivo aspects of neuroscience drug discovery. When the site closed in as an indirect consequence of the Merck blockbuster drug Vioxx being taken off the market, I joined Janssen Pharmaceuticals, the pharmaceutical arm of Johnson & Johnson, where I worked from 2006 to 2012 (initially in La Jolla and then, attracted by the beer, chips and chocolate, in Beerse, Belgium).
I left the pharmaceutical industry to join the University of Sussex to help establish, with Prof. Simon Ward, the Sussex Drug Discovery Centre which, along with the addition of Prof. Martin Gosling gained a reputation for neuroscience drug discovery and ion channel pharmacology in particular.
In summer 2017, Simon and myself chose to move to Cardiff, attracted by the excellence of the disease mechanism and clinical science and the quality and collaborative spirit of the investigators with whom we will be interacting. However, we maintain our contacts with Martin who remains a key collaborator and allows us to expand our interest in ion channel pharmacology.
I am currently engaged in projects identifying molecules that interact with specific subtypes of the GABAA receptor or the AMPA subtype of glutamate receptor. These projects involve multidisciplinary teams of scientists using innovative medicinal chemistry (led by Prof. Simon Ward) and electrophysiology (Profs. Martin Gosling and Jerry Lambert and the University of Sussex and Dundee University, respectively) as well as a number of industrial collaborators (e.g., GSK and AstraZeneca).
I am also involved in a number of additional early-stage projects studying the mechanism of action of lithium and the role of ApoE4 in Alzheimer’s disease as well as novel approaches to modulating NMDA and kainate glutamate ion channel function.
I am driven by the desire to develop new treatments for the neurodegenerative and psychiatric disorders that have a profound impact on so many of our families and for which there remains a significant unmet medical need.