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Prof David Lomas
Appointment
  • Vice-Provost Health
  • VP: Health
  • Office of the President & Provost
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 appointments: Professor of Medicine and Dean of the Faculty of Medical Sciences, UCL 2013-2015; 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 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 Head of UCL Medical School (2014-) and was Co-Director of the UCL Wellcome Trust PhD programme for Clinicians (2013-15). I provide bed-side teaching for medical students on the Respiratory Unit at UCLH.


Declaration of interests  1.1.16
Salary: University College London, MRC  (from 1.4.2012-31.3.16), NIHR
Hon. Consultant: UCLH and Royal Free Hospital

Current grant funding:
MRC, Wellcome Trust, GlaxoSmithKline, NIHR. Rose trees Trust. EPSRC.

Editorial Boards: Am. J. Resp. Cell Mol Biol. 2007-;  J. COPD Found. 2013-

Government: Chair, MRC Population and Systems Medicine Board and member of MRC Strategy Board 2012-2016.  Scientific Advisory Committee Genomics England 2013-. Member, Expert Advisory Group, Innovative Medicines and MedTech Review 2015-16. 

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, GSK 1999-2004. Steering committee, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, GSK 2006-. Board member, GSK Respiratory Centre of Excellence in Drug Discovery 2008-2011. Chair, GSK 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.

Other: Non-executive director UCLH 2015-18; Director of GMEC 2015-; Founders Board Francis Crick Institute 2015-.

Academic Background
2007 FHEA Fellowship of the Higher Education Academy – Academic studies in Higher Education University College London
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