Summary
Research Interests
- Molecular physico-chemical processes in metabolism and medicine
- Development of novel spectroscopic and chemometric tools for investigating human disease and toxicological mechanisms
- Metabolism-driven top-down systems biology and modelling of complex system failure
- Personalised healthcare through metabolic phenotyping and systems medicine
- Surgical metabonomics, real-time diagnostics and integrative patient modelling
Membership of societies
- Fellow of the Academy of Medical Sciences
- Fellow of the Society of Biology
- Fellow of the Royal College of Pathologists
- Fellow of the Royal Society of Chemistry
- Fellow of the British Toxicological Society
- Member of the Imperial College Data Science Institute Research Board
- Elected Honorary Fellow of the Royal College of Physicians
selected honours and awards etc.
The Royal Society of Chemistry: 21st Silver Medal for Analytical Science (1992)
The Chromatographic Society: Jubilee Silver Medal (1994)
The Royal Society of Chemistry: 21st SAC Gold Medal for Analytical Chemistry (1997)
Pfizer Academic Innovation Award for Chemical and Medicinal Technology (2002)
The Royal Society of Chemistry: Silver Medal for Chemical Biology (2003)
Pfizer Global Chemistry Discipline Prize (2006)
The Royal Society of Chemistry Theophilus Redwood Lecturer (2007)
The Royal Society of Chemistry Interdisciplinary Award (2008)
NIH: Stars in Cancer and Nutrition Distinguished Lecturer (2010)
Semmelweis - Budapest Prize (2010)
Robert Zhong Award in Surgery (Canada) (2013)
Honorary Professor of Systems Biology, Shanghai Jiao Tong University (2005)
Honorary Professor of Analytical Chemistry, Chinese Academy of Sciences, Dalian, China (2005)
Honorary Professor of Chemistry, Tsinghua University, Beijing, China (2005)
Honorary Professor of Medicine, Zhe Jaing University, Hongzhou, China (2006)
Honorary Professor of Systems Biology Shanghai TCM University, China (2006)
Honorary Professor of Biological Spectroscopy, State Key Laboratory of Magnetic Resonance and Molecular & Atomic Physics, Chinese Academy of Sciences, Wuhan, China (2006)
Honorary Director of the Metabonomics Research Centre, Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.(2006)
Honorary Director of Wuhan Magnetic Resonance Research Centre, Chinese Academy of Sciences, Dalian, China (elected 2009)
Lifetime Honorary Fellow of the Metabolomics Society (2013)
Lifetime Honorary Member of the US Society of Toxicology (2013)
Robert E Stowell Lectureship, University of California, Davis, USA (2014)
Elected Einstein Professor of the Chinese Academy of Sciences (2014)
Warren Lecturer, Vanderbilt University, USA (2015)
Honorary Professor, University of New South Wales, Sydney, Australia (2015)
External Scientific duties
Consulting Editor: Journal of Proteome Research (ACS)
Editorial Board: Molecular Systems Biology
Spin off company
Non-Executive (Founder) Director, Metabometrix UK Ltd.
Host-Gut Microbiota Metabolic Interactions
The gut microbiota co-evolves with its human host from birth or even in-utero. Factors such as the mode of birth, diet and other environmental stimuli influence the developing composition of the microbiome. Interaction between the human host and its’s microbiome is mediated via several axes of communication including the immune system, signalling and direct metabolic cross-talk that physiologically connect the gut with the brain, muscle and liver. A deeper understanding of these axes provides a new framework for developing novel therapeutic targets and optimising personalised interventions.
The missing link between stunted growth and diet
Kwashiorkor is a severe form of malnutrition commonly encountered in developing countries. Much effort has been placed on trying to find appropriate and low resource nutritional protocols for overcoming malnutrition. Gnotobiotic mice implanted with the faeces of Malawian infant twins discordant for kwashiorkor showed differences in growth in these animals with mice implanted with faeces from the healthy twin gaining more weight. These mice also demonstrated perturbations in amino acid, carbohydrate and TCA metabolism, which were apparent when the mice were placed on a traditional Malawian diet, but largely resolved when the mice were fed with a protein enriched diet. This research adds further weight to the literature emphasising the importance of the microbiome in processing of nutrients and recovery of energy from the diet.
Surgical Metabonomics
By focusing multiple metabolic measuring technologies on the patient at any one moment during their surgical pathway, the quality and depth of prognostic or diagnostic information can also be increased. Several powerful spectroscopic techniques are suitable for surgical metabonomic implementation driven by improved analytical performance and size/cost reductions. We aim to use a combination of NMR and MS technologies to provide unique phenotypic information on the tissue state of the patient and to generate new in situbiomarker diagnostics to help the surgeon where there is an unmet medical need. Magic angle spinning (MAS) NMR spectroscopy is well suited to real-time surgical investigations as no sample preparation is required and allows collection of diagnostic information on pin-head size pieces of tissue biopsy material.
The Patient Journey
Metabolic phenotypes and profiles are modulated by interactions of genes, diet and symbiotic gut microorganismsand influence an individual’s recovery from any therapeutic intervention. Moreover, metabolic phenotypes are responsive to, and predictive of, interventional outcomes. These molecular signatures are data-rich and provide sensitive, specific and efficient vehicles for delivering metabolic phenotype information to aid clinical decision-making. Hence we are initiating a new paradigm for patient stratification based on modelling multi-level patient phenotypes, which could beneficially influence patient outcomes by improving optimisation of therapeutic strategies. Thus, we propose a new vision for improving the patient pathway (See figure), initially focussing on colon and breast cancer but later extending to other areas of oncology. This programme harmonises current scientific and clinical expertise across a range of disparate disciplines and projects, and will provide a vehicle for implementation of these translational molecular approaches in our clinical units.
Selected Publications
Journal Articles
Ruffieux H, Hanson AL, Lodge S, et al., 2023, A patient-centric modeling framework captures recovery from SARS-CoV-2 infection, Nature Immunology, Vol:24, ISSN:1529-2908, Pages:349-+
Nitschke P, Lodge S, Hall D, et al., 2022, Direct low field J-edited diffusional proton NMR spectroscopic measurement of COVID-19 inflammatory biomarkers in human serum., Analyst, Vol:147, ISSN:0003-2654, Pages:4213-4221
Yeap BB, Marriott RJ, Manning L, et al., 2022, Higher premorbid serum testosterone predicts COVID-19-related mortality risk in men., European Journal of Endocrinology, Vol:187, ISSN:0804-4643, Pages:159-170
Loo RL, Chan Q, Nicholson JK, et al., 2022, Balancing the equation: a natural history of trimethylamine and trimethylamine-N-oxide., Journal of Proteome Research, Vol:21, ISSN:1535-3893, Pages:560-589
Masuda R, Lodge S, Whiley L, et al., 2022, Exploration of Human Serum Lipoprotein Supramolecular Phospholipids Using Statistical Heterospectroscopy in n-Dimensions (SHY-n): Identification of Potential Cardiovascular Risk Biomarkers Related to SARS-CoV-2 Infection., Anal Chem
Nitschke P, Lodge S, Kimhofer T, et al., 2022, J-edited dIffusional proton nuclear magnetic resonance spectroscopic measurement of glycoprotein and supramolecular phospholipid biomarkers of inflammation in human serum., Analytical Chemistry, Vol:94, ISSN:0003-2700, Pages:1333-1341
Masuda R, Lodge S, Nitschke P, et al., 2021, Integrative Modeling of Plasma Metabolic and Lipoprotein Biomarkers of SARS-CoV-2 Infection in Spanish and Australian COVID-19 Patient Cohorts, Journal of Proteome Research, Vol:20, ISSN:1535-3893, Pages:4139-4152
Gray N, Lawler NG, Zeng AX, et al., 2021, Diagnostic potential of the plasma lipidome in infectious disease: application to acute SARS-CoV-2 infection, Metabolites, Vol:11, ISSN:2218-1989, Pages:1-17
Wei GZ, Martin KA, Xing PY, et al., 2021, Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor, Proceedings of the National Academy of Sciences of the United States of America, Vol:118, ISSN:0027-8424, Pages:1-10
Bergamaschi L, Mescia F, Turner L, et al., 2021, Longitudinal analysis reveals that delayed bystander CD8<sub>+</sub> T cell activation and early immune pathology distinguish severe COVID-19 from mild disease, Immunity, Vol:54, ISSN:1074-7613, Pages:1257-+
Holmes E, Wist J, Masuda R, et al., 2021, Incomplete Systemic Recovery and Metabolic Phenoreversion in Post-Acute-Phase Nonhospitalized COVID-19 Patients: Implications for Assessment of Post-Acute COVID-19 Syndrome, Journal of Proteome Research, Vol:20, ISSN:1535-3893, Pages:3315-3329
Lawler NG, Gray N, Kimhofer T, et al., 2021, Systemic perturbations in amine and kynurenine metabolism associated with acute SARS-CoV-2 infection and inflammatory cytokine responses, Journal of Proteome Research, Vol:20, ISSN:1535-3893, Pages:2796-2811
Lodge S, Nitschke P, Kimhofer T, et al., 2021, Diffusion and relaxation edited proton NMR spectroscopy of plasma reveals a high-fidelity supramolecular biomarker signature of SARS-CoV-2 infection, Analytical Chemistry, Vol:93, ISSN:0003-2700, Pages:3976-3986
Lodge S, Nitschke P, Kimhofer T, et al., 2021, NMR spectroscopic windows on the systemic effects of SARS-CoV-2 infection on plasma lipoproteins and metabolites in relation to circulating cytokines., Journal of Proteome Research, Vol:20, ISSN:1535-3893, Pages:1382-1396
Nicholson JK, 2021, Molecular Phenomic Approaches to Deconvolving the Systemic Effects of SARS-CoV-2 Infection and Post-acute COVID-19 Syndrome., Phenomics, Vol:1, Pages:143-150
Gray N, Lawler NG, Yang R, et al., 2020, A simultaneous exploratory and quantitative amino acid and biogenic amine metabolic profiling platform for rapid disease phenotyping via UPLC-QToF-MS, Talanta, ISSN:0039-9140
Loo RL, Lodge S, Kimhofer T, et al., 2020, Quantitative In-Vitro Diagnostic NMR Spectroscopy for Lipoprotein and Metabolite Measurements in Plasma and Serum: Recommendations for Analytical Artifact Minimization with Special Reference to COVID-19/SARS-CoV-2 Samples, Journal of Proteome Research, Vol:19, ISSN:1535-3893, Pages:4428-4441
Vonhof EV, Piotto M, Holmes E, et al., 2020, Improved spatial resolution of metabolites in tissue biopsies using high-resolution magic-angle-spinning slice localization NMR spectroscopy., Analytical Chemistry, Vol:92, ISSN:0003-2700, Pages:11516-11519
Kimhofer T, Lodge S, Whiley L, et al., 2020, Integrative modelling of quantitative plasma lipoprotein, metabolic and amino acid data reveals a multi-organ pathological signature of SARS-CoV-2 infection, Journal of Proteome Research, Vol:19, ISSN:1535-3893, Pages:4442-4454
Garcia Perez I, Posma JM, Serrano Contreras JI, et al., 2020, Identifying unknown metabolites using NMR-based metabolic profiling techniques, Nature Protocols, Vol:15, ISSN:1750-2799, Pages:2538-2567
Posma JM, Garcia Perez I, Frost G, et al., 2020, Nutriome-metabolome relationships provide insights into dietary intake and metabolism, Nature Food, Vol:1, ISSN:2662-1355, Pages:426-436
Garcia Perez I, Posma JM, Chambers E, et al., 2020, Dietary metabotype modelling predicts individual responses to dietary interventions, Nature Food, Vol:1, ISSN:2662-1355, Pages:355-364
Kundu P, Lee HU, Garcia-Perez I, et al., 2019, Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice., Science Translational Medicine, Vol:11, ISSN:1946-6234, Pages:1-13
Lahiri S, Kim H, Garcia-Perez I, et al., 2019, The gut microbiota influences skeletal muscle mass and function in mice, Science Translational Medicine, Vol:11, ISSN:1946-6234
Jimenez B, Holmes E, Heude C, et al., 2018, Quantitative lipoprotein subclass and low molecular weight metabolite analysis in human serum and plasma by 1H NMR spectroscopy in a multilaboratory trial, Analytical Chemistry, Vol:90, ISSN:0003-2700, Pages:11962-11971
Hoyles L, Fernández-Real JM, Federici M, et al., 2018, Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women, Nature Medicine, Vol:24, ISSN:1078-8956, Pages:1-17
Inglese P, McKenzie JS, Mroz A, et al., 2017, Deep learning and 3D-DESI imaging reveal the hidden metabolic heterogeneity of cancer, Chemical Science, Vol:8, ISSN:2041-6539, Pages:3500-3511
Wilson ID, Nicholson JK, 2016, Gut microbiome interactions with drug metabolism, efficacy, and toxicity, Translational Research, Vol:179, ISSN:1931-5244, Pages:204-222
Nicholson JK, Holmes E, Kinross J, et al., 2012, Host-gut microbiota metabolic interactions., Science, Vol:336, Pages:1262-1267
Swann JR, Want EJ, Geier FM, et al., 2011, Systemic gut microbial modulation of bile acid metabolism in host tissue compartments, Proceedings of the National Academy of Sciences of the United States of America, Vol:108, ISSN:0027-8424, Pages:4523-4530
Clayton TA, Baker D, Lindon JC, et al., 2009, Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism, Proceedings of the National Academy of Sciences of the United States of America, Vol:106, ISSN:0027-8424, Pages:14728-14733
Claus SP, Tsang TM, Wang Y, et al., 2008, Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes, Molecular Systems Biology, Vol:4
Martin F-PJ, Wang Y, Sprenger N, et al., 2008, Top-down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model, Molecular Systems Biology, Vol:4, ISSN:1744-4292
Holmes E, Loo RL, Stamler J, et al., 2008, Human metabolic phenotype diversity and its association with diet and blood pressure, Nature, Vol:453, ISSN:0028-0836, Pages:396-U50
Li M, Wang B, Zhang M, et al., 2008, Symbiotic gut microbes modulate human metabolic phenotypes, Proceedings of the National Academy of Sciences of the United States of America, Vol:105, ISSN:0027-8424, Pages:2117-2122
Martin F-PJ, Wang Y, Sprenger N, et al., 2008, Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model, Molecular Systems Biology, Vol:4, ISSN:1744-4292
Clayton TA, Lindon JC, Cloarec O, et al., 2006, Pharmaco-metabonomic phenotyping and personalized drug treatment, Nature, Vol:440, ISSN:0028-0836, Pages:1073-1077
Nicholson JK, Holmes E, Wilson ID, 2005, Gut microorganisms, mammalian metabolism and personalized health care, Nature Reviews Microbiology, Vol:3, ISSN:1740-1526, Pages:431-438
Nicholson JK, Connelly J, Lindon JC, et al., 2002, Metabonomics: a platform for studying drug toxicity and gene function, Nature Reviews Drug Discovery, Vol:1, ISSN:1474-1776, Pages:153-161
Gavaghan CL, Holmes E, Lenz E, et al., 2000, An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences:: application to the C57BL10J and Alpk:ApfCD mouse, FEBS Letters, Vol:484, ISSN:0014-5793, Pages:169-174
Nicholson JK, Lindon JC, Holmes E, 1999, 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data, Xenobiotica, Vol:29, ISSN:0049-8254, Pages:1181-1189
Liu ML, Nicholson JK, London JC, 1996, High-resolution diffusion and relaxation edited one- and two-dimensional H-1 NMR spectroscopy of biological fluids, Analytical Chemistry, Vol:68, ISSN:0003-2700, Pages:3370-3376
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NICHOLSON JK, FOXALL PJD, SPRAUL M, et al., 1995, 750-MHZ H-1 AND H-1-C-13 NMR-SPECTROSCOPY OF HUMAN BLOOD-PLASMA, Analytical Chemistry, Vol:67, ISSN:0003-2700, Pages:793-811
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