Shankar-Hari Group

Manu Shankar-Hari leads this translational research group.

Shankar-Hari group’s research explores ways to improve outcomes in adult critically ill patients with sepsis and with ARDS, by linking the illness immunobiology with novel interventional trial designs.

Our lab has the following focussed research themes

Immunobiology: Explore adaptive immune system changes during sepsis, during ARDS and longer-term in patients who survive sepsis. We integrate orthogonal multilevel data with repeated measurements of cellular phenotype, functional assessments, alongside corresponding transcriptomes and epigenetic landscapes.
Epidemiology and Stratified medicine: We use early-phase randomised controlled trials, cohort studies, systematic reviews and large clinical trial datasets to (a) explore treatment effect heterogeneity; (b) identify treatable traits based on dominant biological mechanisms, and (c) modifiable proximate determinants of sepsis and ARDS.

Current PhD students

Rohit Saha
Matthew Fish

Members

Michael Carter

NIHR Academic Clinical Lecturer in Paediatrics

Yasmeen Ghnewa

Post Doctoral Researcher

Aislinn Jennings

Research Assistant

Rohit Saha

Consultant in Intensive Care Medicine

Manu Shankar-Hari

NIHR Clinician Scientist, Reader and Consultant in Intensive Care Medicine

Pneumococcal VACcination to accelerate Immune Recovery in Sepsis Survivors: randomized placebo-controlled trial: VACIRISS trial

Sepsis survivors are at much higher risk of infection-related rehospitalisation and death. The aim of VACIRiSS trial is to evaluate the immunogenicity of single-dose 13-valent conjugate pneumococcal vaccine in preventing infection-related rehospitalisation or death in sepsis survivors and to collect outcome event data with the necessary precision to inform future definitive trial design.

VACIRISS trial

Cellular and molecular mechanisms of IMMunE dysfunction and Recovery from SEpsis related critical illness: an observational cohort study (IMMERSE)

IMMERSE study aims to integrate orthogonal multi-omics datasets of longitudinal (repeated) measurements of key lymphocyte phenotype, immune response signalling proteins, transcriptome and epigenome to describe the main patterns of immune trajectory. The ultimate goal is to inform future immunomodulation trials and aims to use T cell exhaustion as an example.

Defining ARDS and sepsis sub-phenotypes: a re-analysis of two trials to inform stratified medicine approach with future trials

Acute Respiratory Distress Syndrome (ARDS) and sepsis are the two most common illnesses in the critically ill, with increasing incidence and high mortality and many statistically negative trials. This research programme aims to identify homogenous groups (sub-phenotypes) such as patients with clinical or biological features or treatment response characteristics to inform future trial design by enriching patient populations likely to benefit the most from interventions.

Relationship between eligibility criteria in randomised controlled trials and ARDS clinical criteria on outcomes

Using systematic review, meta-analysis, cohort studies and risk modelling approaches, Rohit’s PhD aims to explain the impact of trial eligibility criteria on variability in outcomes between ARDS trials, variability in treatment effect between trials, sample size estimations, and evaluated design biases. The ultimate goal is to identify parsimonious variables that will improve future ARDS trial design.

Is T Cell Exhaustion a Treatable Trait in Sepsis? 12 February 2020

Rate and risk factors for rehospitalisation in sepsis survivors: systematic review and meta-analysis 23 January 2020

Demographic Shifts, Case Mix, Activity, and Outcome for Elderly Patients Admitted to Adult General ICUs in the United Kingdom, Wales, and Northern Ireland 09 January 2020

Maternal Risk Modeling in Critical Care-Development of a Multivariable Risk Prediction Model for Death and Prolonged Intensive Care 09 January 2020

Should we consider blocking the inhibitory immune checkpoint molecules for treating T cell exhaustion in sepsis? 01 January 2020

Trials on oxygen supplementation in sepsis: better late than never 01 January 2020

Current gaps in sepsis immunology: new opportunities for translational research 01 December 2019

Sepsis hysteria: excess hype and unrealistic expectations 26 October 2019

Focus on sepsis 01 October 2019

Population enrichment for critical care trials: phenotypes and differential outcomes 01 October 2019

View all research outputs

2017 2022 NIHR Clinician Scientist Award, National Institute for Health Research