Key research themes

(see Figure 1)

• Maternal sepsis (mSEP)
• Neonatal sepsis (nSEP)
• Paediatric sepsis (pSEP)
• Adult sepsis (aSEP)

Areas of expertise

Prof Peter Ghazal (n,p,aSEP) - Chief Investigator and academic lead for n, pSEP

I previously led the Division of Pathway Medicine at the University of Edinburgh.

Watch a video of me talking about the research I carried out into Neonatal Medicine whilst there.

My research interests are aimed towards understanding how host-gene networks control infection, especially with those host-pathways associated with sepsis and the immune-metabolic axis. My recent studies have pioneered the field of host genomics of early-life infection, mapping and deciphering gene metabolic signatures of systemic host response to infection in pre-term infants and neonates and understanding the molecular wiring and mechanisms for coupling lipid metabolism to immune (interferon) response.

These studies are specifically aimed at the development of new diagnostic and therapeutic strategies, including predictive modelling of host-defence against infection in sepsis, and the development of new computational and functional genomic methods for gaining a deeper understanding of complex dynamical biological systems of viral (cytomegaloviral) and microbial diseases.

Prof Valerie O’Donnell (n,p,aSEP) - Principle Investigator and academic lipid metabolism lead

Our current research is focused on understanding the role of lipids (fats) in vascular inflammation, a major complicating factor in sepsis and driver of multi-organ failure. Lipids are generated by circulating blood cells and platelets in response to blood infection. These stimulate clotting and cell damage, and dampening these processes while allowing the body to control the infection itself is a major goal of our research.

We have identified large numbers of new lipids made in blood cells and understanding their biological functions is a core research goal. Delineating how lipids and energy metabolites interface during sepsis to control inflammation and blood clotting is essential if we are to develop new prevention and treatment approaches.

Dr Mallinath Chakraborty (nSEP) - Clinical lead

My interests are in neonatal respiratory medicine and sepsis. I am the local Principal Investigator for several multi-centre clinical trials and am developing my own research group. I also run the respiratory module of the Masters in Neonatal Medicine at Cardiff University.

Dr Claire Smith (nSEP) - Edinburgh

My research interest is in neonatal infection with on-going involvement in studies in this area. I am actively involved in the local neonatal unit infection surveillance programme and have played a significant part in introducing a successful infection reduction programme to the neonatal unit.

Prof Timothy Walsh (n,pSEP) - Principle Investigator

I am director of BARNARDS, a BMFG funded project examining the burden of neonatal sepsis in Nigeria, Pakistan, Bangladesh, Rwanda and Ethiopia. I am also PI of DETER-XDR-China and CUT-SEC that examines the one health approach to studying AMR in China, Vietnam and Thailand.

I am an advisor on AMR to the United Nations, Médecins Sans Frontières and the Fleming Fund.

Prof B Paul Morgan - Principle Investigator

I am an expert in the complement system, a critical component of innate immunity and a powerful driver of inflammation. Dysregulation of the complement system has been implicated in sepsis and systemic inflammatory response syndromes; indeed, complement markers in blood have been used to predict and monitor these conditions. Critically, an emerging wave of anti-complement drugs may provide new ways of breaking the cycle of inflammation in patients with sepsis.

Dr Martin Edwards (pSEP) - Clinical lead

My research interest in is paediatric epidemiology and how to improve healthcare services for the most vulnerable. I completed my PhD on the outcomes of infants born preterm focusing on their respiratory illnesses.

I am currently involved with paediatric sepsis research and have an interest in developing a national paediatric clinical research database.

Dr Paul Morgan (aSEP) - Principal Investigator

As an Intensive Care consultant and the Lead Volunteer in Wales for the UK Sepsis Trust, sepsis makes up a substantial part of my work.

My interests in sepsis has led me to try to drive change in sepsis recognition and care outside the critical care environment, working with staff from primary and secondary care so that sepsis can be spotted early, enabling timely intervention and thereby reduce the need for critical care admission. Ultimately, my hope is that this will reduce not just mortality from sepsis but also the morbidity, which results in long-term health problems for sepsis survivors. I am a member of the steering committee and co-author of the papers that have been published from the Size of Sepsis in Wales and the Defining Sepsis in the Wards point prevalence studies.

Dr Matthias Eberl (aSEP) - Principle Investigator and Academic lead of aSEP

My interdisciplinary research aims to characterise early immune responses in acutely ill patients and define pathogen-specific signatures of cellular and soluble biomarkers ('immune fingerprints'). This work has direct implications for improved diagnosis and treatment of microbial infections including sepsis.

Dr Matthew Morgan (aSEP) - Clinical lead

Intensive care doctor, scientist, computer programmer, teacher and geek interested in machine learning, medical education and public engagement. My PhD used artificial intelligence to tease out “immune fingerprints” from different types of life-threatening infections.

I have spent time training in the UK, Australia and the military. Passionate about critical care medicine and intensive care research, I also work with the British Medical Journal to improve medical education, healthcare IT and research outcomes.

Dr Robert Andrews (n,p,aSEP) - Informatics lead

My interests are in the information management and analysis of large biomedical datasets. As part of my role, I design and build compute infrastructure for handling high-throughput ‘big-data’. Specifically, project sepsis will deploy a biomedical informatics framework for the capturing, querying, retrieval and sample tracking of clinical and laboratory research information with which to automate and manage novel microfluidic approaches aimed toward advancing innovative precision diagnostic tests and treatments for sepsis.

I also teach chromatin informatics with the Wellcome Trust advanced courses and lead the omics module on the MSc in Bioinformatics at the University.

Rhian Thomas-Turner (n,p,aSEP) - R&D Operations Manager

I am the R&D Operations Manager for the Noah’s Ark Children’s Hospital for Wales. My role involves both the strategic and operational oversight of research within the Children’s Hospital and running the newly establish Children and Young Adults’ Research Unit.   The aim of the Unit is to act a hub for high quality Child Health research in Wales.

Dr Widad Dantoft (n,p,aSEP) - Research Associate

My research interest lies in understanding the intricate interplay between immunity and metabolism in the presence of viral (CMV) and bacterial infections, and how this affects the infection process and outcome.  I am in particularly interested in how this immune-metabolic interplay is regulated on a transcriptional level.

Dr Jenna Bowen - Lecturer, Cardiff School of Pharmacy and Pharmaceutical Sciences

My research interests lie in the field of sepsis and infection, with a particular focus on the development of bio-sensing systems to enable rapid diagnosis, patient stratification and personalisation of therapies. I enjoy working across disciplines and have established collaborations across life science and engineering / physical science disciplines as well as with end-users from the clinical, commercial and third sector in order to deliver fit-for-purpose technologies.

I am also a co-founder of a start-up company, Cotton Mouton Diagnostics (CMD), which is developing a diagnostic platform that can be deployed across a range of healthcare settings.

Dr Tamas Szakmany - Critical Care Consultant, Senior Lecturer and Director of Critical Illness Research

In collaboration with Public Health England and industry (Randox and Atlas Genetics) I have led Innovate UK funded multicentre clinical trials on adult sepsis. These studies identified mRNA and protein biomarker panels that distinguish sepsis from non-infective origin of organ dysfunction for use with point-of-care devices.

I further designed and led an award winning (Cardiff University Excellence in teaching award 2017 and NHS Wales Award runner-up 2016) collaboration with the Cardiff University Research Society for medical students, establishing the burden of sepsis on the general wards and Emergency Departments in Wales. These multi-centre point-prevalence studies recruited over 1000 patients quantifying the incidence when using different clinical scores to define sepsis.

Dr Mario Labeta (aSEP) - Senior Lecturer

My current work focuses on the immunobiology of the Toll-like family of immune receptors (TLRs) as mediators of immune and inflammatory responses. Following our discovery of a soluble form of TLR2 (sTLR2) in blood that has anti-inflammatory capacity, we are evaluating whether plasma sTLR2 may be used as a biomarker for sepsis, as opposed to SIRS and other serious infections. In collaboration with a Welsh biotech company (JRBiomedical, Glyndwr University) we are developing a fast point-of-care test to determine plasma levels of sTLR2.

In further work we have identified TLR2-derived peptides capable of boosting the immune response of immunosuppressed sepsis patients ex vivo, and currently seeking to stratify sepsis patient subgroup(s) that may therapeutically benefit from our TLR-based peptide strategy.

Dr Daniel White - Senior Innovation and Technology Scientist

With over 20 years of experience in lipid biology and analytical chemistry, spanning scientific fields from environmental monitoring to biomedical research, my role role in Project Sepsis is to develop high-throughput lipidomic profiling strategies to determine robust biomarkers of sepsis in the systemic circulation of patients. These methods are part of integrative strategy for understanding the casual link between metabolism and the immune response in determining sepsis patient outcome and together with clinical team members will be translated to the clinical care pathway for improving precision in identifying and treating those patients presenting with suspected sepsis.

Dr James McLaren - Sêr Cymru Lecturer in Systems Immunity

My research interests focus on understanding how adaptive immune responses (T cell driven) are mobilised during viral (HIV, cytomegalovirus) and microbial infections, inflammation and disease. Furthermore, I have a keen interest in discovering how this type of cellular immunity is regulated by biological signals (cytokines) and how it can destabilise when global immune responses become imbalanced, such as in sepsis. As part of Project Sepsis, my aim is to deconvolute the immunological mechanisms that drive the suppression of adaptive immunity in sepsis with a view to help improve diagnosis and to inform the design of novel therapeutic interventions.

Dr Jason Twohig - Lecturer in Medical Transcriptomics

I utilise novel ‘OMICs’ approaches to facilitate the identification and stratification of patients with chronic disease for effective therapeutic treatment with biologics. I am particularly interested in identifying blood transcriptomic signatures which predict the presence of SEPSIS, its progress, its mechanism, and its resolution. More broadly, my research interests also include understanding the role of cytokines in inflammation and homeostasis in the immune and neurological system during development and infection.

Linda Moet

My background is a Bachelor in Medical Biology and a Master in Biomedicine. What fascinates me most is how complex systems in the body are regulated and interact, especially the immune system and the gut microbiota. My PhD is focused on the G-Protein coupled receptor (GPR) 84. This receptor has only been discovered quite recently; it is present on various immune cells and binds medium chain fatty acids. These come (most likely) from breast milk in the neonatal context. The receptor thus connects metabolism and diet with immunity. Since its expression is upregulated during neonatal sepsis, we decided to investigate the role of GPR84-signalling during neonatal sepsis, the presence and effects of its ligands and their potential origins. Hopefully this project will further the understanding of sepsis leading to better diagnosis and treatment in the future.

Simran Sharma

I am very excited to be joining project sepsis as a clinician as I see the detrimental impact of sepsis on mothers and babies every day. An opportunity to learn more through research is something I am very much looking forward to.

Our international community

Professor Tobias Strunk (nSEP) - Clinical Associate Professor, Centre for Neonatal Research and Education (The University of Western Australia, Perth, Australia) and Neonatal Directorate, King Edward Memorial Hospital (Perth, Australia)

My research interest is the immunological determinants of newborn
susceptibility to invasive bacterial infection and novel prophylactic
and therapeutic interventions to reduce disease burden, areas highly  relevant to the current proposal.

EU NeoVanc Project

Clinical trial assessing the dosage of vancomycin antibiotic in the treatment of late onset bacterial sepsis caused by vancomycin susceptible bacteria in neonates and infants aged under three months.

Project members

• Prof Carlo Giaquinto (University of Padova, Head of Paediatrics AIDS centre, Italy)
• Profs Mike Sharland  (St. Georges, University of London, Head of Paediatrics, UK)
• Prof Paul Heath (St. Georges, University of London, Paediatric infectious diseases, UK)
• Prof EvelyneJacqz-Aigrain (Robert Debre Hospital, Head of Paediatric pharmacology, France)
• Prof Irji Lutsar (University of Tartu, Head of Department of clinical microbiology, Estonia)
• Prof. Baiardi (Consorzio per Valutazioni Biologiche e Farmacologiche, Director Biostatistics, Italy)
• Dr. Mark Turner (University of Liverpool, Consultant neonatologist, UK)
• Prof Peter Ghazal (University of Edinburgh & University of Cardiff medical schools, Chief investigator project-sepsis)

Selected publications

• Dantoft, W. et al. 2017. Genomic programming of human neonatal dendritic cells in congenital systemic and in vitro cytomegalovirus infection reveal plastic and robust immune pathway biology responses. Frontiers in Immunology 8 1146. (10.3389/fimmu.2017.01146)
• Zhang, J. et al. 2017. Machine-learning algorithms define pathogen-specific local immune fingerprints in peritoneal dialysis patients with bacterial infections. Kidney International 92 (1), pp.179-191. (10.1016/j.kint.2017.01.017)
• Raby, A. et al. 2017. Toll-like receptors 2 and 4 are potential therapeutic targets in peritoneal dialysis-associated fibrosis. Journal of the American Society of Nephrology 28 (2), pp.461-478. (10.1681/ASN.2015080923)
• Holst, B. et al., 2017. Soluble toll-like receptor 2 is a biomarker for sepsis in critically ill patients with multi-organ failure within 12 h of ICU admission. Intensive Care Medicine Experimental 5 (1)(10.1186/s40635-016-0116-z)
• Liuzzi, A. R. et al. 2016. Unconventional human T cells accumulate at the site of infection in response to microbial ligands and induce local tissue remodeling. Journal of Immunology 197 (6), pp.2195-2207. (10.4049/jimmunol.1600990)
• Raby, A. and Labeta, M. 2016. Therapeutic boosting of the immune response: turning to CD14 for help. Current Pharmaceutical Biotechnology 17 (5), pp.414-418. (10.2174/1389201017666160114095708)
• Duffin, R. et al., 2016. Prostaglandin E2 constrains systemic inflammation through an innate lymphoid cell-IL-22 axis. Science 351 (6279), pp.1333-1338. (10.1126/science.aad9903)
• Morgan, M. et al. 2016. Sepsis patients with first and second-hit infections show different outcomes depending on the causative organism. Frontiers in Microbiology 7 207. (10.3389/fmicb.2016.00207)
• Dickinson, P. et al., 2014. Whole blood gene expression profiling of neonates with confirmed bacterial sepsis. Genomics Data 3 , pp.41-48. (10.1016/j.gdata.2014.11.003)
• Eberl, M. et al. 2014. Pathogen-specific immune fingerprints during acute infection: The diagnostic potential of human γδ T-cells. Frontiers in Immunology 5 572. (10.3389/fimmu.2014.00572)
• Davey, M. S. et al., 2014. Microbe-specific unconventional T cells induce human neutrophil differentiation into antigen cross-presenting cells. The Journal of Immunology 193 (7), pp.3704-3716. (10.4049/jimmunol.1401018)
• Smith, C. L. et al., 2014. Identification of a human neonatal immune-metabolic network associated with bacterial infection. Nature Communications 5 (10.1038/ncomms5649)
• Raby, A. et al. 2013. Targeting the TLR co-receptor CD14 with TLR2-derived peptides modulates immune responses to pathogens. Science Translational Medicine 5 (185) 185ra64. (10.1126/scitranslmed.3005544)

Associated staff

Sepsis Engagement Centre

We seek to promote interaction between patients, researchers, and clinical staff through the Sepsis Engagement Centre, physically located in the Sir Geraint Evans Cardiovascular Research Building, acting as an interaction and training hub. Planned audio-visual exhibitions include “The sepsis life cycle”, an exhibition of simulation wards with featured displays of neonatal intensive care unit (NICU), paediatric intensive care unit (PICU), adult intensive care unit (ICU), and an exhibit for scientific understanding of current and planned future medical tests and treatments for sepsis.

The Sepsis Engagement Centre aims to engage through outreach events and to promote patient and public involvement (PPI) for making a real difference in our research and the clinic for saving lives against sepsis.

Read more about the preview event that was held for the Sepsis Engagement Centre on 20 June 2018.

A community action for getting involved to be involved in sepsis awareness and research

Central to helping us reach our goals are Lay Advisory groups for neonatal, paediatric, and adult sepsis, respectively. The role of our Lay Advisory groups is to help review research priorities, identify new lines of research, give input into research proposals (lay summaries in particular) and impact statements and website content, as well as contributes to the dissemination of research findings to relevant target groups.

Lay advisory involvement for project sepsis is underway with opportunities to join the pool of lay advisors in our community action against sepsis. We especially welcome those affected by sepsis either directly, as former patients, or indirectly as family members of former patients as well as those who wish to get involved out of general interest.

If you would like to find out more about patient and public engagement, please contact: projectsepsis@cardiff.ac.uk

Our lay advisory community

• Terence Canning (aSEP)
• Nicola Madoc-Jones (nSEP)
• David Madoc-Jones (nSEP)
• Holly Powell (nSEP)
• Tracey Laight (aSEP)
• Jacqueline Mason (aSEP)
• Alan Brown (aSEP)