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

Members

Michael Carter

NIHR Academic Clinical Lecturer in Paediatrics

Silvia Cellone Trevelin

Research Associate

Rohit Saha

Consultant in Intensive Care Medicine

Manu Shankar-Hari

Professor in Critical Care Medicine and NIHR Clinician Scientist

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.

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial
Gorman, E., Shankar-Hari, M., Hopkins, P., Tunnicliffe, W. S., Perkins, G. D., Silversides, J., McGuigan, P., Jackson, C., Boyle, R., McFerran, J., McDowell, C., Campbell, C., McFarland, M., Smythe, J., Thompson, J., Williams, B., Curley, G., Laffey, J. G., Clarke, M., McAuley, D. F., & 1 othersO’Kane, C., Dec 2022, In: Trials. 23, 1, 401. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1186/s13063-022-06220-0
Towards a biological definition of ARDS: are treatable traits the solution?
Bos, L. D. J., Laffey, J. G., Ware, L. B., Heijnen, N. F. L., Sinha, P., Patel, B., Jabaudon, M., Bastarache, J. A., McAuley, D. F., Summers, C., Calfee, C. S. & Shankar-Hari, M., Dec 2022, In: Intensive Care Medicine Experimental. 10, 1, 8. Research output: Contribution to journal › Review article › peer-review. DOIs: https://doi.org/10.1186/s40635-022-00435-w
The Impact of Sample Size Misestimations on the Interpretation of ARDS Trials: systematic review and meta-analysis
Saha, R., Assouline, B., Mason, G., Douiri, A., Summers, C. & Shankar-Har, M., Nov 2022, In: Chest. 162, 5, p. 1048-1062 15 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1016/j.chest.2022.05.018
Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex
Patone, M., Mei, X. W., Handunnetthi, L., Dixon, S., Zaccardi, F., Shankar-Hari, M., Watkinson, P., Khunti, K., Harnden, A., Coupland, C. A. C., Channon, K. M., Mills, N. L., Sheikh, A. & Hippisley-Cox, J., 6 Sep 2022, In: Circulation. 146, 10, p. 743-754 12 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1161/CIRCULATIONAHA.122.059970
Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline
Møller, M. H., Alhazzani, W., Lewis, K., Belley-Cote, E., Granholm, A., Centofanti, J., McIntyre, W. B., Spence, J., Al Duhailib, Z., Needham, D. M., Evans, L., Reintam Blaser, A., Pisani, M. A., D’Aragon, F., Shankar-Hari, M., Alshahrani, M., Citerio, G., Arora, R. C., Mehta, S., Girard, T. D., & 6 othersRanzani, O. T., Hammond, N., Devlin, J. W., Shehabi, Y., Pandharipande, P. & Ostermann, M., Jul 2022, In: Intensive Care Medicine. 48, 7, p. 801-810 10 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1007/s00134-022-06660-x
Disrupted Peyer’s patch microanatomy in COVID-19 including germinal centre atrophy independent of local virus
Cellone Trevelin, S., Pickering, S., Todd, K., Bishop, C., Pitcher, M., Garrido Mesa, J., Montorsi, L., Spada, F., Petrov, N., Green, A., Shankar-Hari, M., Neil, S. & Spencer, J., 27 Jan 2022, (Accepted/In press) In: Frontiers in Immunity- sub specialisation, Mucosal Immunity. Research output: Contribution to journal › Article › peer-review
ARDS subphenotypes: Searching for Rorschach among the roentgenograms?
Conway Morris, A., Kohler, K. & Shankar-Hari, M., 1 Jan 2022, In: Thorax. 77, 1, p. 2-4 3 p. Research output: Contribution to journal › Editorial › peer-review. DOIs: https://doi.org/10.1136/thoraxjnl-2021-217428
A guide to immunotherapy for COVID-19
van de Veerdonk, F. L., Giamarellos-Bourboulis, E., Pickkers, P., Derde, L., Leavis, H., van Crevel, R., Engel, J. J., Wiersinga, W. J., Vlaar, A. P. J., Shankar-Hari, M., van der Poll, T., Bonten, M., Angus, D. C., van der Meer, J. W. M. & Netea, M. G., Jan 2022, In: Nature Medicine. 28, 1, p. 39-50 12 p. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1038/s41591-021-01643-9
Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial
the REMAP-CAP Immunoglobulin Domain UK Investigators, 2022, (Accepted/In press) In: Intensive Care Medicine. Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1007/s00134-022-06869-w
Towards an ecological definition of sepsis: a viewpoint
Bauer, M., Shankar-Hari, M., Thomas-Rüddel, D. O. & Wetzker, R., 29 Dec 2021, In: Intensive Care Medicine Experimental. 9, 1, p. 63 Research output: Contribution to journal › Article › peer-review. DOIs: https://doi.org/10.1186/s40635-021-00427-2

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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

UK Research and Innovation (UKRI)

Huo Family Foundation

Guy's and St Thomas' Charity

Department of Health & Social Care

Group lead

Manu Shankar-Hari

Professor in Critical Care Medicine and NIHR Clinician Scientist

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

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial

Towards a biological definition of ARDS: are treatable traits the solution?

The Impact of Sample Size Misestimations on the Interpretation of ARDS Trials: systematic review and meta-analysis

Risk of Myocarditis After Sequential Doses of COVID-19 Vaccine and SARS-CoV-2 Infection by Age and Sex

Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline

Disrupted Peyer’s patch microanatomy in COVID-19 including germinal centre atrophy independent of local virus

ARDS subphenotypes: Searching for Rorschach among the roentgenograms?

A guide to immunotherapy for COVID-19

Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial

Towards an ecological definition of sepsis: a viewpoint

European Society of Intensive Care Medicine

UK Intensive Care Society

News coverage of research

JAMA Sepsis Webpage highlighting 2016 definitions

Our partners

Group lead

Manu Shankar-Hari

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Study at King’s

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Shankar-Hari Group

Members

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

Group lead

Contact us

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