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The William Harvey Research Institute - Barts and The London

Professor Mark Griffths

Honorary Clinical Professor (Centre for Microvascular Research), Consultant Physician (St Bartholomew’s Hospital)

Centre: Centre for Microvascular Research

Email: m.griffiths@ic.ac.uk, mark.griffiths@bartshealth.nhs.uk

Profile

MG is a founder member of the UK and Ireland Acute Lung Injury Research Group and Chair of the Intensive Care Society Guideline Development group for the Management of ARDS.  His clinical and research interests are in acute lung injury, alveolar epithelial cell responses to injury and ICU acquired weakness.

Memberships/Awards

International

  • Visiting Professor
    Van Andel Institute, Grand Rapids, Michigan, USA 2017 
  • Faculty & Speaker, International Meetings
    Toronto ARDS 2016
    10th Int. Conference: Cachexia, Sarcopenia & Muscle Wasting, Rome 2017

National

  • Authorships & Editing
    Chair & lead author: ICS Management of ARDS guidelines 2018, presented ICS SOA meeting 2017, podcast 2018
    Thorax (impact factor 8.272) Associate Editor 2015-
    Over 20 book chapters (see below)
  • British Thoracic Society
    Council Member 2017- Research & Meetings Committee
  • Founder of the UK Acute Lung Injury research group
    - 5 meetings including international speakers 2008-18
    - first joint BTS/ICS session at ICS winter meeting 2011
    - 4 university chairs
    - 4 phase 3 trials HARP, BREATH, REST, BALTI prevention

Local

  • Chair Critical Care Medicine at Imperial College 2015 & Queen Mary University London 2016
    Director of Research, St Barts Peri-Operative Medicine 2016
    NIHR Office for Clinical Research Infrastructure (NOCRI) Translational Research Partnerships in Inflammatory Respiratory Disease, Intensive Care Experimental Medicine Group, Barts Health Lead (2016-)

Research

Group members

Aemun Salam Academic Clinical Fellow, Supervised with Adrian Hobbs.
Ashley Thomas, Clinical Research Fellow, Supervised with Julie Sanders.

Summary 

My research interest is the response of the lung and skeletal muscle to injury, particularly insults associated with critical illness, which compliments my role as an intensivist. I have used in vitro, ex vivo and human models, as well as clinical material from patients to:

1. uncover the pathogenesis of ventilator-associated lung injury (VALI) with the aim of discovering novel targets for treatment, and biomarkers with prognostic and therapeutic significance

2. investigate the complications of using extracorporeal devices, the purpose of which is to mitigate VALI

3. discover epigenetic determinants of individual suceptibility to muscle wasting in intensive care unit associated weakness (ICUAW)

4. investigate in survivors of critical illness, how ICUAW influences their recovery of independence & quality of life

With the UK ECMO community, we initiated a landmark study demonstrating a survival benefit associated with the use of extracorporeal membrane oxygenation (ECMO) in patients with influenza-associated ARDS. This body of research has helped to underpin the importance of VALI in the outcome of critical illness, has promoted the widespread use of protective ventilation strategies and has contributed to the increased use of extracorporeal devices to support patients with ARDS.

We have identified epigenetic determinants (microRNAs) of muscle wasting in acute & chronic disease. We are investigating the effectiveness of corresponding antagomirs in an animal model, as the first step towards translation into patients with ICUAW.

Key Publications

  • Proudfoot A, Bayliffe A, O'Kane CM, Wright T, Serone A, Bareille PJ, Brown V, Hamid UI, Chen Y, Wilson R, Cordy J, Morley P, de Wildt R, Elborn S, Hind M, Chilvers ER, *Griffiths M, *Summers C, *McAuley DF. Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury. Thorax. 2018 Jan 29. pii: thoraxjnl-2017-210305. doi: 10.1136/thoraxjnl-2017-210305. PMID:29382797 *These authors contributed equally 
  • Paul R, Lee J, Donaldson AV, Connolly M, Sharif M, Natanek SA, Rosendahl U, Polkey MI, Griffiths M, Kemp PR. miR-422a suppresses SMAD4 protein expression and promotes resistance to muscle loss. J Cachexia Sarcopenia Muscle. 2018 Feb;9(1):119-128. doi: 10.1002/jcsm.12236. PMID: 28984049
  • Connolly M, Paul R, Farre-Garros R, Natanek SA, Bloch S, Lee J, Lorenzo JP, Patel H, Cooper C, Sayer AA, Wort SJ, Griffiths M, Polkey MI, Kemp PR. miR-424-5p reduces ribosomal RNA and protein synthesis in muscle wasting. J Cachexia Sarcopenia Muscle. 2017 Dec 7. doi: 10.1002/jcsm.12266. PMID: 9215200
  • Garros RF, Paul R, Connolly M, Lewis A, Garfield BE, Natanek SA, Bloch S, Mouly V, Griffiths MJ, Polkey MI, Kemp PR. MicroRNA-542 Promotes Mitochondrial Dysfunction and SMAD Activity and Is Elevated in Intensive Care Unit-acquired Weakness. Am J Respir Crit Care Med. 2017 Dec 1;196(11):1422-1433. doi: 10.1164/rccm.201701-0101OC. PMID:28809518
  • Poobalasingam T, Yates LL, Walker SA, Pereira M, Gross NY, Ali A, Kolatsi-Joannou M, Jarvelin MR, Pekkanen J, Papakrivopoulou E, Long DA, Griffiths M, Wagner D, Königshoff M, Hind M, Minelli C, Lloyd CM, Dean CH. Heterozygous Vangl2Looptail mice reveal novel roles for the planar cell polarity pathway in adult lung homeostasis and repair. Dis Model Mech. (2017) 10(4):409-423. doi: 10.1242/dmm.028175. PMID:28237967
  • Ng-Blichfeldt JP, Alçada J, Montero MA, Dean CH, Griesenbach U*, Griffiths MJ*, Hind M*. Deficient retinoid-driven angiogenesis may contribute to failure of adult human lung regeneration in emphysema. Thorax (2017) 72(6):510-521. doi: 10.1136/thoraxjnl-2016-208846. PMID: 28087752 *These authors contributed equally
  • Bastin AJ, Davies N, Lim E, Quinlan GJ, Griffiths MJ. Systemic inflammation and oxidative stress post-lung resection: Effect of pretreatment with N-acetylcysteine. Respirology (2016) 21(1):180-7. doi: 10.1111/resp.12662. PMID: 26503312
  • Bloch SA, Donaldson AV, Lewis A, Banya WA, Polkey MI*, Griffiths MJ*, Kemp PR*. MiR-181a: a potential biomarker of acute muscle wasting following elective high-risk cardiothoracic surgery. Critical Care (2015) 19(1):147. PMID:25888214. *These authors contributed equally
  • Park JE, Lyon AR, Shao D, Hector LR, Xu H, O'Gara P, Pinhu L, Chambers RC, Wort SJ, Griffiths MJ. Pulmonary venous hypertension and mechanical strain stimulate monocyte chemoattractant protein-1 release and structural remodelling of the lung in human and rodent chronic heart failure models. Thorax (2014) 69(12): 1120-7. doi: 10.1136/thoraxjnl-2013-204190.
  • Bloch SA, Lee JY, Syburra T, Rosendahl U, Griffiths MJ*, Kemp PR*, Polkey MI*. Increased expression of GDF-15 may mediate ICU-acquired weakness by down-regulating muscle microRNAs. Thorax (2014) 70(3): 219-28. doi: 10.1136/thoraxjnl-2014-206225. *These authors contributed equally

Sponsors

Nourshargh, Sussan

  • *Pfizer unrestricted grant (2013-4) £133,962. Preclinical models of COPD
  • * Imperial Confidence in Concepts – Biomedical Research Centre/ Innovations Primer Fund (2013-4) £50,087. Development of the haemolysis triple filter
  • Wellcome Trust: CTF (2013 – 2015) £226,110.  Integrin-associated proteins in VALI
  • *NHLI Studentship (2014-17) £176,000 Role of Dishevelled activator of morphogenesis genes 1 & 2 in lung development and repair
  • *NIHR pump prime (2014-5) £10,000 A triple filter device to protect against the adverse effects of haemolysis in stored blood
  • *NIHR pump prime (2014-5) £14,500 Does the expression of imprinted micro RNAs in the muscle or plasma predict muscle wasting in intensive care unit acquired muscle weakness
  • *NIHR HTA programme (2015-20) £2,125,511 PRotective vEntilation with veno-venouS lung assisT in respiratory failure: the REST Trial
  • NIHR Doctoral Exchange Training Scheme (Royal Brompton Harefield & Southampton University Respiratory Biomedical Research Units (BRU: 2015) £4,956.48
  • *NC3Rs Project Grant (2016-9) £497,719 Human Tissue Models for Lung Disease NC/P001041/1
  • Barts Charity: CTF (2017 – 2020) £180,000.  Molecular determinants of recovery from ICU acquired weakness and its effects on quality of life
  • *MRC & GSK EMINENT: Project Grant (2016-9) £1,000,000. Stratified Interventions in ARDS
  • *GSK: (2017-8)  £188,477 Biomarkers of muscle wasting following cardiac surgery
  • *Apollo Therapeutics (2017-18) £37,500 AntagomiRs of miR-542 and miR-424 as anti-atrophic agents; a pilot study.

* co-applicant, otherwise lead/PI

Collaborators

  • Sussan Nourshagh, Adrian Hobbs, Julie Sanders (WHRI)
  • Paul Kemp, Mike Polkey, Matt Hind, Charlotte Dean, Vania Braga (Imperial College)
  • Danny McAuley (Belfast)
  • Charlotte Summers (Cambridge)
  • David Thickett (Birmingham)
  • John Simpson (Newcastle)