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.
COVID-19 research focuses on clinical trials, translational immunology and children with PIMS-TS illness: Translational immunology in adults focuses on how the immune system responses are influenced by treatment with convalescent plasma and recombinant interleukin-7 in the respective clinical trials.

Current PhD students

Rohit Saha

Matthew Fish

Aislinn Jennings

Members

Michael Carter

NIHR Academic Clinical Lecturer in Paediatrics

Silvia Cellone Trevelin

Research Associate

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.

COVID-19 research focuses on clinical trials, translational immunology and children with PIMS-TS illness

Translational immunology in adults focuses on how the immune system responses are influenced by treatment with convalescent plasma and recombinant interleukin-7 in the respective clinical trials.

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans
Seow, J., Graham, C., Merrick, B., Acors, S., Pickering, S., Steel, K. J. A., Hemmings, O., O'Byrne, A., Kouphou, N., Galao, R. P., Betancor, G., Wilson, H. D., Signell, A. W., Winstone, H., Kerridge, C., Huettner, I., Jimenez-Guardeño, J. M., Lista, M. J., Temperton, N., Snell, L. B. & 22 others, Bisnauthsing, K., Moore, A., Green, A., Martinez, L., Stokes, B., Honey, J., Izquierdo-Barras, A., Arbane, G., Patel, A., Tan, M. K. I., O'Connell, L., O'Hara, G., MacMahon, E., Douthwaite, S., Nebbia, G., Batra, R., Martinez-Nunez, R., Shankar-Hari, M., Edgeworth, J. D., Neil, S. J. D., Malim, M. H. & Doores, K. J., 26 Oct 2020, In : Nature Microbiology. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1038/s41564-020-00813-8
Paediatric Inflammatory Multisystem Syndrome Temporally-Associated with SARS-CoV-2 Infection: An Overview
Carter, M. J., Shankar-Hari, M. & Tibby, S. M., 14 Oct 2020, In : Intensive Care Medicine. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1007/s00134-020-06273-2
COVID-19 in critical care: epidemiology of the first epidemic wave across England, Wales and Northern Ireland
ICNARC COVID-19 Team, 9 Oct 2020, In : Intensive Care Medicine. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1007/s00134-020-06267-0
A dynamic COVID-19 immune signature includes associations with poor prognosis
Laing, A. G., Lorenc, A., del Molino del Barrio, I., Das, A., Fish, M., Monin, L., Muñoz-Ruiz, M., McKenzie, D. R., Hayday, T. S., Francos-Quijorna, I., Kamdar, S., Joseph, M., Davies, D., Davis, R., Jennings, A., Zlatareva, I., Vantourout, P., Wu, Y., Sofra, V., Cano, F. & 30 others, Greco, M., Theodoridis, E., Freedman, J., Gee, S., Chan, J. N. E., Ryan, S., Bugallo-Blanco, E., Peterson, P., Kisand, K., HaljasmÃ¤gi, L., Chadli, L., Moingeon, P., Martinez, L., Merrick, B., Bisnauthsing, K., Brooks, K., Ibrahim, M. A. A., Mason, J., Lopez Gomez, F., Babalola, K., Abdul-Jawad, S., Cason, J., Mant, C., Seow, J., Graham, C., Doores, K. J., Di Rosa, F., Edgeworth, J., Shankar-Hari, M. & Hayday, A. C., 1 Oct 2020, In : Nature Medicine. 26, 10, p. 1623-1635 13 p. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1038/s41591-020-1038-6
Development, Validation, and Clinical Utility Assessment of a Prognostic Score for 1-Year Unplanned Rehospitalization or Death of Adult Sepsis Survivors
Shankar-Hari, M., Rubenfeld, G. D., Ferrando-Vivas, P., Harrison, D. A. & Rowan, K., 14 Sep 2020, In : JAMA Network open. 3, 9, p. e2013580 Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1001/jamanetworkopen.2020.13580
Outcomes in mechanically ventilated patients with hypoxaemic respiratory failure caused by COVID-19
Camporota, L., Sanderson, B., Dixon, A., Vasques, F., Jones, A. & Shankar-Hari, M., 3 Sep 2020, In : British Journal of Anaesthesia. Research output: Contribution to journal - Letter. DOIs: https://doi.org/10.1016/j.bja.2020.08.047
Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19
Jaunmuktane, Z., Mahadeva, U., Green, A., Sekhawat, V., Barrett, N. A., Childs, L., Shankar-Hari, M., Thom, M., JÃ¤ger, H. R. & Brandner, S., 1 Sep 2020, In : Acta Neuropathologica. 140, 3, p. 397-400 4 p. Research output: Contribution to journal - Letter. DOIs: https://doi.org/10.1007/s00401-020-02190-2
Use of Hydrocortisone Based on Plasma Biomarkers in Patients with Septic Shock: Another One Bites the Dust?
MÃ¸ller, M. H., Shankar-Hari, M. & Alhazzani, W., 1 Sep 2020, In : American Journal of Respiratory and Critical Care Medicine. 202, 5, p. 644-646 3 p. Research output: Contribution to journal - Editorial. DOIs: https://doi.org/10.1164/rccm.202005-1984ED
Translational Research in the Time of COVID-19-Dissolving Boundaries
Edgeworth, J. D., Batra, R., Nebbia, G., Bisnauthsing, K., MacMahon, E., Sudhanva, M., Douthwaite, S., Goldenberg, S., O'Hara, G., Shankar-Hari, M., Doores, K. J., Martinez-Nunez, R., Hemsley, C., Price, N. M., Lockett, J., Lechler, R. I., Neil, S. J. D. & Malim, M. H., Sep 2020, In : PLoS Pathogens. 16, 9, p. e1008898 e1008898. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1371/journal.ppat.1008898
Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection
Carter, M. J., Fish, M., Jennings, A., Doores, K. J., Wellman, P., Seow, J., Acors, S., Graham, C., Timms, E., Kenny, J., Neil, S., Malim, M. H., Tibby, S. M. & Shankar-Hari, M., 18 Aug 2020, In : Nature Medicine. Research output: Contribution to journal - Article. DOIs: https://doi.org/10.1038/s41591-020-1054-6

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

UK2018 2019 Lowry Fink Fellowship, International Sepsis Forum

2017 Global Rising Star in Intensive Care, Australia and New Zealand Intensive Care Society

Health Technology Assessment programme (2019 – 2025)

Efficacy and Mechanism Evaluation Programme (2019-2021)

Efficacy and Mechanism Evaluation Programme (2017-2019)

National Institute for Health Research Clinician Scientist Award (2017-2022)

BJA/RCoA PhD studentship (2019-2022 )

Kings Commercialisation Institute Challenge Fund (2015-2016)

Our partners

National Institute for Health Research

Medical Research Council

National Institute of Academic Anaesthesia

Contact us

manu.shankar-hari@kcl.ac.uk

Shankar-Hari Group

Members

Michael Carter

Silvia Cellone Trevelin

Rohit Saha

Manu Shankar-Hari

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

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

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

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

COVID-19 research focuses on clinical trials, translational immunology and children with PIMS-TS illness

Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

Paediatric Inflammatory Multisystem Syndrome Temporally-Associated with SARS-CoV-2 Infection: An Overview

COVID-19 in critical care: epidemiology of the first epidemic wave across England, Wales and Northern Ireland

A dynamic COVID-19 immune signature includes associations with poor prognosis

Development, Validation, and Clinical Utility Assessment of a Prognostic Score for 1-Year Unplanned Rehospitalization or Death of Adult Sepsis Survivors

Outcomes in mechanically ventilated patients with hypoxaemic respiratory failure caused by COVID-19

Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19

Use of Hydrocortisone Based on Plasma Biomarkers in Patients with Septic Shock: Another One Bites the Dust?

Translational Research in the Time of COVID-19-Dissolving Boundaries

Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection

European Society of Intensive Care Medicine

UK Intensive Care Society

News coverage of research

JAMA Sepsis Webpage highlighting 2016 definitions

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Shankar-Hari Group

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

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

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

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

COVID-19 research focuses on clinical trials, translational immunology and children with PIMS-TS illness

European Society of Intensive Care Medicine

UK Intensive Care Society

News coverage of research

JAMA Sepsis Webpage highlighting 2016 definitions

Our partners

Contact us

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