Imperial College London

ProfessorJeremyNicholson

Faculty of MedicineDepartment of Surgery & Cancer

Chair in Biological Chemistry, Head of Department
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

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

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

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.

ost-Gut Microbiota Metabolic Interactions

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.

stunted growth

 

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.

lab

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.

Patient Journey

Selected Publications

Journal Articles

Sands CJ, Coen M, Ebbels TMD, et al., 2011, Data-Driven Approach for Metabolite Relationship Recovery in Biological H-1 NMR Data Sets Using Iterative Statistical Total Correlation Spectroscopy, Analytical Chemistry, Vol:83, ISSN:0003-2700, Pages:2075-2082

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

Heinzmann SS, Brown IJ, Chan Q, et al., 2010, Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption, American Journal of Clinical Nutrition, Vol:92, ISSN:0002-9165, Pages:436-443

Fonville JM, Maher AD, Coen M, et al., 2010, Evaluation of Full-Resolution J-Resolved H-1 NMR Projections of Biofluids for Metabonomics Information Retrieval and Biomarker Identification, Analytical Chemistry, Vol:82, ISSN:0003-2700, Pages:1811-1821

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

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

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, ISSN:1744-4292

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

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

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