Professor Mark Griffths

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 susceptibility 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.

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

Collaborators

Internal

• Sussan Nourshagh (WHRI)
• Adrian Hobbs (WHRI)
• Julie Sanders (WHRI)

External

• Paul Kemp, Mike Polkey, Matt Hind, Charlotte Dean, Vania Braga (Imperial College)
• Danny McAuley (Belfast)
• Charlotte Summers (Cambridge)
• David Thickett (Birmingham)
• John Simpson (Newcastle)