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Prof David Lomas
Appointment
  • Dean of Medical Sciences
  • Faculty of Medical Sciences
  • School of Life & Medical Sciences
Role
Dean
 
 
Biography

Bachelor of Medical Sciences (Honours), University of Nottingham. 1983.

Bachelor of Medicine, Bachelor of Surgery (Honours), University of Nottingham. 1985

MRCP (UK), 1988.

PhD, Trinity College, University of Cambridge. 1993.

FRCP (Lond.), 1997.

Member of the Institute of Learning and Teaching, 2000.

Fellow of the Academy of Medical Sciences, 2001.  

ScD.  Trinity College, University of Cambridge, 2004.

Fellow of the Higher Education Academy, 2007.

Previous appointment: Professor of Respiratory Biology/Honorary Consultant Physician, University of Cambridge, 1998-2012.  Deputy Director, Cambridge Institute for Medical Research, 2002-2012. Fellow, St. John's College 2008-2012.

Research Groups
Research Summary

I undertook my PhD with Professor Robin Carrell FRS in the Department of Haematology at the University of Cambridge. My work demonstrated that the Z mutation of α1-antitrypsin caused the protein to undergo a novel conformational transition and form chains of polymers that are retained within hepatocytes. It is these polymers that underlie the PAS positive inclusions that characterise the condition. I showed that this same process was important in the retention of the Siiyama, Mmalton, S and I variants of α1-antitrypsin that also cause hepatic inclusions and plasma deficiency. My research team expressed, purified, characterised and crystallised wildtype and mutants of α1-antitrypsin and developed monoclonal antibodies and cell based assays to elucidate the pathway by which polymers form in vitro and in vivo. We also assessed a variety of strategies to block polymerisation that included the use of chaperones, competition with blocking peptides, in silico screens for small molecules that bind to novel allosteric pockets that we identified in our crystal structures, and more recently stem cell technology. 

The process of polymerisation is not unique to α1-antitrypsin but occurs in other members of the serine protease inhibitor (serpin) superfamily. Mutants of α1-antichymotrypsin, antithrombin, C1-inhibitor and heparin co-factor II were described by my team, and by others, that form polymers in vitro and in vivo. This is associated with emphysema, thrombosis and angiodema respectively. Perhaps most striking was our description of this process in neuroserpin to form inclusions within neurones and an autosomal dominant dementia that we named familial encephalopathy with neuroserpin inclusion bodies or FENIB. In view of the common mechanism linking all these diseases we have grouped them together as a new class of disorder that we have termed the serpinopathies. We have used our understanding of the serpinopathies to provide insights into other conformational diseases such as Alzheimer's, Huntington's and Parkinson's disease and the prion encephalopathies. The recognition that point mutations in neuroserpin underlie the dementia FENIB led us to assess the role of this protein in the more common dementia associated with Alzheimer's disease. We were able to demonstrate that neuroserpin is present in the plaques of individuals with Alzheimer's disease, that it forms a one-to-one interaction with the Aβ peptide and that it reduces the toxicity of this peptide in vitro and in a Drosophila model of disease. Our Drosophila model of Alzheimer's disease showed striking neurodegeneration and we therefore used it for a genetic screen to identify modifiers of the toxicity mediated by the Aβ peptide. Our data show a clear role for oxidative stress in neurodegeneration. Moreover we have collaborated with Chris Dobson's group (Chemistry, Cambridge) to use this model to develop algorithms of peptide toxicity in vitro and in vivo. 

Alpha-1-antitrypsin deficiency is the only genetic factor that is widely accepted to predispose to COPD. The identification of novel genetic factors will provide new insights into the pathobiology of this disease. I have therefore worked with Ed Silverman (Harvard) to establish the International COPD Genetics Network that was funded by GSK. This network was used to demonstrate independent familial aggregation of the airway and emphysema components of COPD and to assess candidate genes in association studies. It has recently been used in GWAS to identify SNPs in the nicotinic acetylcholine receptor, the hedgehog interacting protein (HHIP) and FAM13A as being associated with COPD.

Teaching Summary

I am Director of the UCL Wellcome Trust PhD programme for Clinicians and provide bed-side teaching for medical students on the Respiratory Unit at UCLH.


Declaration of interests  1st January 2014 
Salary: University College London, Medical Research Council (from 1st April 2012-), National Institute for Health Research
Honorary Consultant: UCLH and Royal Free Hospital

Current grant funding:
Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences Research Council, GlaxoSmithKline, National Institute for Health Research, Children's Liver Disease Foundation

Learned societies: Fellow, Royal College of Physicians. Member, British Thoracic Society. Member, Association of Physicians. Fellow, Academy of Medical Sciences

Editorial Boards: American Journal of Respiratory Cell and Molecular Biology 2007-;  J of the COPD Foundation 2013-

Government: Chair, MRC Population and Systems Medicine Board (PSMB) and member of MRC Strategy Board 2012-2016.  Scientific Advisory Committee Genomics England 2013-

Charities:  Steering committee COPD Biomarkers Qualification Consortium (US COPD Foundation) 2010-. Patron, Alpha-1 Awareness UK 2011-. Honorary Senior Treasurer, National Student Association of Medical Research 2011-

Industry boards and significant associations: Co-lead PI, International COPD Genetics Network, GlaxoSmithKline 1999-2004. Steering committee, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, GlaxoSmithKline 2006-. Board member, GlaxoSmithKline Respiratory Centre of Excellence in Drug Discovery 2008-2011. Chair, GlaxoSmithKline Respiratory Therapy Area Board 2012-2015

Industry sponsored meetings/grants committee: Grants committee Alpha-one antitrypsin Laurell Training Award (ALTA) funded by Talecris 2004-2011 and now Grifols 2012-. 

Consultancies/honoraria/travel 2005- GlaxoSmithKline, Novartis, Amicus,  Talecris,  AstraZeneca, Genzyme,  LFB,  Boehringer Ingelheim

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