Bibek Gooptu

Contact details:

Tel: 0116 229 7137

Email: bg129@le.ac.uk

Personal details

  • BSc (Hons) Biomedical Science, intercalated within Preclinical Medicine, University of Manchester (1992-1995)
  • MBBChir and PhD, Christ’s College and Department of Medicine, University of Cambridge (1995-2000)
  • Junior medical career (House Officer to Specialist Registrar): Addenbrooke’s Hospital Cambridge (2000, 2010-12); Queen’s Medical Centre, Nottingham (2001-03);  Royal Brompton Hospital, London (2003-4, 2009-10); Southend and Broomfield Hospitals, Essex (2004-06); University College London Hospital (2006-09); Guy’s & St Thomas’ Hospitals, London (2009)
  • Wellcome Trust Intermediate Clinical Fellow and Department of Health National Clinician Scientist Awardee, Institute of Structural & Molecular Biology (ISMB), Birkbeck College and UCL (2006-11, Honorary Research Fellow since 2012)
  • Consultant Physician, Papworth Hospital (2012)
  • Senior Clinical Lecturer, Divisions of Asthma, Allergy & Lung Biology and Randall Division of Cell & Molecular Biophysics, King’s College London (2012-2016, Visiting Professorship since 2017)
  • Honorary Consultant Physician, Guy’s & St Thomas’ Hospitals, (2012-2016)
  • Honorary Consultant Physician, Royal Free Hospital London, (Since 2013)
  • Professor of Respiratory Biology, University of Leicester UK (Since 2016)
  • Consultant Physician, Glenfield Hospital, Leicester (Since 2016)

Publications

Management of Idiopathic Pulmonary Fibrosis
DAD Bruce-Hickman, H Garthwaite, M Heightman, B Gooptu
Book Chapter in “Clinical Handbook of Interstitial Lung Diseases” 2017 – in press
Eds. M Thillai, D Moller, K Meyer; Taylor & Francis

Alpha1-antitrypsin: structure and dynamics in health, disease and drug development
A Jagger, JA Irving ST Rashid, DA Lomas, B Gooptu
Book Chapter in “Alpha-1 Antitrypsin Deficiency” 2017 – in press
Eds. N Kalsheker and RA Stockley; Elsevier

A multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case cohort study
SLF Walsh, AU Wells, SR Desai, V Poletti, S Piciucchi, A Dubini, H Nunes, D Valeyre, P Brillet, M Kambouchner, A Morais, JM Pereira, CP Souto Moura, JC Grutters, DA van den Heuvel, HW van Es, MF van Oosterhout, CA Seldenrijk, E Bendstrup, F Rasmussen, LB Madsen, B Gooptu, S Pomplun, H Taniguchi, J Fukuoka, T Johkoh, AG Nicholson, C Sayer, L Edmunds, J Jacob, MA Kokosi, JL Myers, KR Flaherty, D Hansell 
Lancet Respiratory Medicine – 4(7):557-65. doi: 10.1016/S2213-2600(16)30033-9. 2016

Update on alpha-1 antitrypsin deficiency: new therapies
DA Lomas, JR Hurst, B Gooptu
Journal of Hepatology – 65(2):413-24, 2016

Aberrant disulphide bonding contributes to the ER retention of alpha1-antitrypsin deficiency variants
R Ronzoni, R Berardelli, D Medicina, R Sitia, B Gooptu, AM Fra
Human Molecular Genetics, 25(4):642-50, doi: 10.1093/hmg/ddv501, 2016

Deficiency mutations of α1-antitrypsin. Effects on folding, function and polymerisation
I Haq, JA Irving, AD Saleh, L Dron, JR Hurst, G Regan-Mochrie, N Motamedi-Shad, B Gooptu§, DA Lomas§
(§ joint senior/corresponding author) 
Am J Resp Cell Mol Biol, 54:71-80. doi: 10.1165/rcmb.2015-0154OC, PMID: 26091018, 2016

Interactions between N-linked glycosylation and polymerisation of neuroserpin within the endoplasmic reticulum
E Miranda, C Moriconi, A Ordóñez, B Gooptu, JA Irving, V Timpano, L Dalton, SJ Marciniak, DA Lomas
FEBS J, 282(23):4565-79 – doi: 10.1111/febs.13517, PMID: 26367528, 2015

Controversies in COPD: α1-antitrypsin deficiency 
D Bruce-Hickman, CM Greene, B Gooptu
European Respiratory Monograph, 2015

Misfolding and polymerisation of 1-antitrypsin – conformational pathology and therapeutic targeting
B Gooptu, DA Lomas
Book Chapter in “Alpha-1 Antitrypsin: Role in Health and Disease” 2015 
Eds. A Wanner and RA Sandhaus; Humana Press

Native ion mobility mass spectrometry, crystallographic and NMR spectroscopic characterisation of α1-antitrypsin conformational dynamics relevant to disease and therapy
MP Nyon, T Prentice, J Day, J Kirkpatrick, G Sivalingam, G Levy, I Haq, JA Irving, DA Lomas, J Christodoulou, B Gooptu§, Konstantinos Thalassinos§ 
(§ joint senior/corresponding author) 
Protein Science, 2015, 24:1301-1312

Associations of latency with 1-antitrypsin polymerisation
L Tan, J Perez, M Mela, E Miranda, KA Burling, FN Rouhani, DL DeMeo, I Haq, JA Irving, A Ordóñez, JA Dickens, M Brantly, SJ Marciniak, GJM Alexander, B Gooptu§, DA Lomas§ 
(§ joint senior/corresponding author) 
International Journal of Biochemistry and Cell Biology, 2015 58:81-91

Tacrolimus in IIM-associated ILD: defining roles and responders
P Gordon and B Gooptu
Rheumatology, 2015 54(1):3-4

Therapeutic targeting of misfolding and conformational change in α1-antitrypsin deficiency
MP Nyon and B Gooptu
Future Medicinal Chemistry, 2014 6:1047-1065

The molecular and cellular pathology of α₁-antitrypsin deficiency
B Gooptu, JA Dickens, DA Lomas
Trends in Molecular Medicine, 2014 20:116-127

Reactive centre loop mutants of α-1-antitrypsin reveal position-specific effects on intermediate formation along the polymerization pathway 
I Haq, JA Irving, SV Faull, JA Dickens, A Ordóñez, D Belorgey, B Gooptu, DA Lomas 
Bioscience Reports, 2013 33:e00046c

Structural dynamics associated with intermediate formation in an archetypal conformational disease
MP Nyon, L Segu, LD Cabrita, G Lévy, J Kirkpatrick, BD Roussel, AOM Patschull, R Kerr, UI Ekeowa, TE Barrett, N Kalsheker, M Hill, K Thalassinos, DA Lomas, J Christodoulou, B Gooptu
Structure 2012, 20:504-12

Three new alpha1-antitrypsin deficiency variants help to define a C-terminal region regulating conformational change and polymerization
AM Fra, B Gooptu, I Ferrarotti, R Scabini, E Miranda, R Ronzoni, F Benini, L Corda, D Medicina, M Luisetti, L Schiaffonati
PLoS ONE 2012: e38405. doi:10.1371/journal.pone.0038405

In silico assessment of potential druggable pockets on the surface of α1-antitrypsin conformers
AOM Patschull, B Gooptu, P Ashford, T Daviter, I Nobeli
PLoS ONE 2012 7: e36612. doi:10.1371/journal.pone.0036612

1H, 15N and 13C backbone resonance assignments of the archetypal serpin α1-antitrypsin
MP Nyon, J Kirkpatrick, LD Cabrita, J Christodoulou, B Gooptu
Biomol NMR Assign. 2012 6:153-6. doi: 10.1007/s12104-011-9345-y

Therapeutic target site variability in α1-antitrypsin characterized at high resolution
AOM Patschull, L Segu, MP Nyon, DA Lomas, I Nobeli, TE Barrett, B Gooptu
Acta Crystallographica F 2011, 67:1492-1497

The structural biology of α1-antitrypsin and the serpinopathies
B Gooptu and DA Lomas
Book chapter in “Methods in Protein Biochemistry”, 2011 Ed. H Tschesche, De Gruyter, Berlin, New York

Targeting serpins in high-throughput and structure-based drug design
YP Chang, R Mahadeva, AOM Patschull, I Nobeli, AR McKay, K Thalassinos, JA Irving, I Haq, MP Nyon, J Christodoulou, UI Ekeowa, A Ordóñez, E Miranda, 
B Gooptu
Methods in Enzymology 2011, 501:139-75

The serpinopathies: Studying serpin polymerisation in vivo
JA Irving, UI Ekeowa, D Belorgey, I Haq, B Gooptu, E Miranda, J Pérez, BD Roussel, A Ordóñez, LE Dalton, SE Thomas, SJ Marciniak, H Parfrey, ER Chilvers, JH Teckman, S Alam, R Mahadeva, ST Rashid, L Vallier, DA Lomas
Methods in Enzymology 2011, 501:421-66

Defining the mechanism of polymerization in the serpinopathies
UI Ekeowa, J Freeke, E Miranda, B Gooptu, M Bush, J Pérez, J Teckman, CV Robinson, DA Lomas
Proceedings of the National Academy of Sciences (USA) 2010, 107:17146-17151

A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with α1-antitrypsin deficiency
E Miranda, J Pérez, UI Ekeowa, N Hadzic, N Kalsheker, B Gooptu, B Portmann, D Belorgey, M Hill, S Chambers, J Teckman, GJ Alexander, SJ Marciniak, DA Lomas
Hepatology 2010, 52: 1078-1088

Alpha1-antitrypsin deficiency, chronic obstructive pulmonary disease and the serpinopathies
UI Ekeowa, B Gooptu, D Belorgey, P Hägglöf, S Karlsson-Li, E Miranda, J Pérez, I MacLeod, H Kroger, SJ Marciniak, DC Crowther, DA Lomas
Clinical Science 2009, 116: 837-850

Mechanisms of emphysema in α1-antitrypsin deficiency: molecular and cellular insights
B Gooptu, UI Ekeowa, DA Lomas
European Respiratory Journal 2009, 34: 475-488

Conformational pathology of the serpins – themes, variations and therapeutic strategies
B Gooptu and DA Lomas
Annual Review of Biochemistry 2009, 78:147-176

Crystallographic and cellular characterisation of two mechanisms stabilising the native fold of alpha1-antitrypsin: implications for disease and drug design
B Gooptu, E Miranda, I Nobeli, M Mallya, AG Purkiss, SC Leigh Brown, C Summers, RL Phillips, DA Lomas, TE Barrett
Journal of Molecular Biology 2009, 387: 865-868

Polymers and inflammation: disease mechanisms of the serpinopathies
B Gooptu and DA Lomas
Journal of Experimental Medicine 2008, 205: 1529-1534

Small molecules block the polymerization of Z α1-antitrypsin and increase the clearance of intracellular aggregates
M Mallya, RL Phillips, SA Saldanha, B Gooptu, SC Leigh Brown, DJ Termine, AM Shirvani, Y Wu, RN Sifers, R Abagyan, DA Lomas
Journal of Medicinal Chemistry 2007, 50: 5357-5363

Oxygen alert cards and controlled oxygen: preventing emergency admissions at risk of hypercapnic acidosis receiving high inspired oxygen concentrations in ambulances and A&E departments
B Gooptu, L Ward, SO Ansari, CD Eraut, D Law, AG Davison
Emergency Medicine Journal 2006, 23:636-638

Nucleation of 1-antichymotrypsin polymerization
DC Crowther, LC Serpell, TR Dafforn, B Gooptu, DA Lomas 
Biochemistry 2003, 42:2355-6

Inactive conformation of the serpin 1-antichymotrypsin indicates two-stage insertion of the reactive loop; implications for the inhibitory function and conformational disease
B Gooptu, B Hazes, W-S W Chang, TR Dafforn, RW Carrell, RJ Read, DA Lomas
Proceedings of the National Academy of Sciences (USA) 2000, 97;67-72

Familial dementia caused by polymerisation of mutant neuroserpin
RL Davis, AE Shrimpton, P Holohan, C Bradshaw, D Feiglin, P Sonderegger, J Kinter, LM Becker, F Lacbawan, D Krasnewich, M Muenke, DA Lawrence, MS Yerby, C-M Shaw, B Gooptu, PR Elliott, JT Finch, RW Carrell, DA Lomas 
Nature 1999, 401:376-378

Conformational changes and disease – serpins, prions and Alzheimer’s
RW Carrell and B Gooptu
Current Opinion in Structural Biology 1998, 8:799-809

Research

  • Diseases mediated by protein misfolding and conformational change, in particular serpinopathies
  • Molecular mechanisms and therapeutic targeting of chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), familial dementia (FENIB) and hepatic fibrosis
  • Multi-platform studies integrating X-ray crystallography, NMR spectroscopy, cryo-EM, computational biology, native mass spectrometry, proteomics, biochemical studies, cell biology and observations in human disease in/ex vivo

My research defines and therapeutically targets molecular mechanisms of diseases within one or both of the following categories: (i) those driven by protein misfolding/conformational change; (ii) those causing chronic lung disease (COPD and ILD).

A longstanding interest has been in studying the structure and biology of the serpin (serine protease inhibitor) superfamily of proteins, and the diseases that arise from mutations causing their misfolding and/or conformational change (serpinopathies).

The combination of biochemical studies, genotype:phenotype correlation in humans, and X-ray crystallography led to key early insights.  More recently, the Gooptu group has applied NMR, native MS and single particle EM to understand how altered structural dynamics are critical to pathological behaviour in serpins, how serpins self-associate into polymers, and to develop small molecules as therapies. In parallel, proteomic studies have defined in unprecedented detail the subcellular consequences of serpin misfolding and conformational change in cell models of the archetypal serpinopathy, 1-antitrypsin deficiency. An ongoing research collaboration further probes how 1-antitrypsin deficiency results in impaired immunomodulation. These studies are supported by the Wellcome Trust, Alpha-1 Foundation, and MRC and CASE studentships.

I am now using similar multi-platform approaches to understand how interactions of the chimaeric protein galectin-3 at the surface of eptihelial and fibroblast cells mediate fibrosis in multiple organs. The disease focus is particularly on the devastating lung condition idiopathic pulmonary fibrosis (IPF). This work is currently supported by start-up funding from the University of Leicester and makes use of the state-of-the-art basic and clinical research facilities at the LISCB, the Advanced Imaging Facility and the NIHR Leicester Respiratory Biomedical Research Centre.

Recent funding

  • Wellcome Trust Programme Grant (as Co-Investigator, Alpha1-antitrypsin deficiency and the serpinopathies)
  • Alpha-1 Foundation Project Grant (Drug discovery in 1-antitrypsin deficiency)
  • Alpha-1 Foundation Pilot Study Grants (as Co-Investigator, Vitamin D, 1-antitrypsin and airway immunomodulation)
  • NIHR Biomedical Research Centre Award (as consortium member, University of Leicester & Glenfield Hospital, Cardiovascular, Lifestyle and Respiratory)
  • MRC Clinical Research Infrastructure award (within KCL consortium, single cell proteomics and genomics)
  • Wellcome Trust Multi-User Equipment Award (within UCL consortium, 2nd generation ion-mobility, Q-ToF Mass Spectrometer)
  • Wellcome Trust Intermediate Clinical Fellowship (X-ray crystallography, NMR spectroscopy and single particle EM studies of serpinopathies)

Share this page:

Contact Details

Department of Molecular and Cell Biology
Henry Wellcome Building
Lancaster Road
Leicester
LE1 7RH (Postal)

LE1 7HB (Sat Nav/Online maps)

T:  +44(0)116 229 7038
F:  +44(0)116 229 7123
MolCellBiol@le.ac.uk

Accessibility

DisabledGo logo

The University of Leicester is committed to equal access to our facilities. DisabledGo has a detailed accessibility guide for the Henry Wellcome Building.

Redfearn Lecture 2017

To Be Confirmed