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UK Dementia Research Institute at UCL

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Prof Paul Whiting

Professorial Research Associate

Department of Neuromuscular Diseases

UCL Queen Square Institute of Neurology

Joined UCL
1st Oct 2015

Research summary

 

1.  The Alzheimer’s Research UK UCL Drug Discovery Institute (DDI).  The overarching goal of the DDI is to develop new therapeutic approaches for dementias.  The unmet medical need is huge, and the rapid advances in our understanding of the pathophysiology of these diseases mean that this is a very exciting time to take on this challenge. We have initiated a number of projects in key areas: protein toxicity; proteostasis; neuroinflammation; synaptic health and maintenance.    Projects broadly have the goal of validating hypotheses around potential drug targets and their role in neurodegenerative disease, and then generating small molecules that appropriately modulate the function of that particular drug target and can be subsequently developed as potential therapeutics.  We have a team of neurobiologists, pharmacologists and medicinal chemists to enable us to progress these projects.  We work very collaboratively: every project is a collaboration with another PI/ group at UCL, or beyond; a number of our projects also involve collaboration with a pharma company, giving us access to unique resources.

As an example, of one of our projects is focused on Wnt signalling in the CNS, and its dysfunction in Alzheimer's disease.  This project is a very exciting collaboration with the Patricia Salinas group at UCL, the JP Vincent group at the Francis Crick Institute, and the Yvonne Jones group in Oxford.  We are defining the role of the Wnt deacetylase Notum, which inactivates Wnt, in the regulation of Wnt signalling in the CNS.  We are particularly interested in its role in modulating neural function in the context of AD.  To do this we are taking a variety of approaches, including mouse genetics, and the development of novel small molecule Notum inhibitors as pharmacological tools.

2. A research programme in the Dementia Research Institute (DRI) at UCL.  This new programme initially focusses upon Wnt signalling in the CNS, and its dysfunction in AD.  One aspect is focussing upon “humanising” our understanding of Wnt signalling in neural systems using iPSC approaches, building upon our expertise in iPSC neuronal disease models.  The second aspect will focus upon brain vascular endothelial cells, key constituents of the blood-brain-barrier, and their dysfunction in AD.  This project is utilising iPSC disease modelling approaches, and in parallel single cell transcriptomics to understand changes in endothelial cell biology in mouse models of AD, and also in human AD tissues.  Both these projects are highly collaborative, with the Salinas and Selina Wray labs at UCL, and the Carlo Sala Frigerio lab within the UCL DRI.

Teaching summary

At UCL Paul teaches on a number of courses, including:

  • "An Introduction to the Mechanisms of Drug Action" for undergraduate Biomedical Sciences students
  • M.Sc. Neurosciences
  • M.Sc. Neuromuscular Diseases
  • Complex - The UCL Centre for Computation, Mathematics and Physics in the Life Sciences and Experimental Biology- postgraduate lecture series

He has previously been, and is currently primary/secondary supervisor to a number of UCL PhD students

Biography

Paul obtained a first class honours degree from the University of Leeds, followed by a PhD at the University of London. He moved to the Salk Institute for Biological Studies in San Diego for his postdoc, before joining the Neuroscience Research Centre, Merck Research Laboratories, where he moved from lab scientist to Head of Molecular and Cellular Neurosciences.

 

Paul joined Pfizer in 2006, and in 2008 helped establish the new Pfizer Regenerative Medicine research unit in Cambridge UK, leading the small molecule and cell therapy programs.  In 2011 the regenerative medicine activities were incorporated into Pfizer Neusentis, where he was Head of Molecular and Cellular Biology until October 2015 when he moved to UCL Institute of Neurology to become the Chief Scientific Officer for the Alzheimer’s Research UK UCL Drug Discovery Institute.  In 2017 he also became a Programme Leader in the UK Dementia Research Institute at UCL.


Paul’s scientific contributions span from ion channel neurobiology, the biology of schizophrenia, pluripotent stem cell based disease modelling through to neurodegenerative diseases. He has lead drug and cell therapy programmes from basic research through to clinical trials, and has co-authored around 200 scientific publications.

 

 He served on a range of advisory boards/committees including the MRC Neuroscience and Mental Health Board, the Biological Sciences committee for assessment of UK University & Research Institutions (RAE 2008) and the Neuroscience, Psychiatry and Psychology committee for assessment of UK University & Research Institutions (REF 2014). He is currently a member of the Parkinson's UK Drug Discovery Panel, MRC Regenerative Medicine Research Committee and MRC UK Regenerative Medicine Platform Board.

Publications