Professor Jeremy K Nicholson
Chair In Biological Chemistry, Head of Department
Department of Surgery & Cancer
Tel: +44 (0)20 7594 3195
Professor Jeremy K Nicholson
- Molecular physio-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.
- Surgical metabonomics, real-time diagnostics and integrative patient modelling.
Membership of societies
Fellow of the Academy of Medical Sciences
Fellow of the Institute of Biology
Fellow of the Royal College of Pathologists
Fellow of the Royal Society of Chemistry
Fellow of the British Toxicological Society
Selected Honours and Awards etc.:
Honorary Professor of Systems Biology, Shanghai Jiao Tong University;
Honorary Professor of Analytical Chemistry, Chinese Academy of Sciences, Dalian, China;
Honorary Professor of Chemistry, Tsinghua University, Beijing, China;
Honorary Professor of Medicine, Zhe Jaing University, Hongzhou, China;
Honorary Professor of Systems Biology Shanghai TCM University, China;
Honorary Professor of Biological Spectroscopy, State Key Laboratory of Magnetic Resonance and Molecular & Atomic Physics, Chinese Academy of Sciences, Wuhan, China;
Honorary Director of the Metabonomics Research Centre, Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China;
Honorary Director of Wuhan Magnetic Resonance Research Centre, Chinese Academy of Sciences, Dalian, China.
Honorary Fellow of the Metabolomics Society
Honorary Member of the US Society of Toxicology
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 Disciplinary Prize (2006)
The Royal Society of Chemistry (2007) - Theophilus Redwood Lecturer
The Royal Society of Chemistry (2008) – Interdisciplinary award
NIH: Stars in Cancer and Nutrition Distinguished Lecturer (2010)
Semmelweis – Budapest Prize (2010)
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 InteractionsThe 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.
Gut microbial influence in melamine toxicity is melamine toxicity.
The recent health scare in China, where there was an outbreak of renal injury leading to death in some infants following ingestion of melamine-tainted milk, was shown to be related to gut microbial activity. Cyanuric acid, responsible for forming renal stones in the renal tubules, is a product of bacterial conversion of melamine. Klebsiella terrigena, isolated from faeces of rats treated with melamine, was shown to directly convert melamine to cyanuric acid. The prevalence of Klebsiella in human infant faeces (ca 1%) approximately matches the percentage of adverse reactions to the melamine-contaminated milk product.
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.
- Sands CJ; Coen M; Ebbels TM; Holmes E; Lindon JC; Nicholson JK. (15 Mar 2011). Data-driven approach for metabolite relationship recovery in biological 1H NMR data sets using iterative statistical total correlation spectroscopy. Anal Chem. 83:2075-2082. Author weblink DOI.
- Swann JR; Want EJ; Geier FM; Spagou K; Wilson ID; Sidaway JE; Nicholson JK; Holmes E. (15 Mar 2011). Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc Natl Acad Sci U S A. 108 Suppl 1:4523-4530. Author weblink DOI.
- Heinzmann SS; Brown IJ; Chan Q; Bictash M; Dumas ME; Kochhar S; Stamler J; Holmes E; et alElliott P; Nicholson JK. (Aug 2010). Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption. Am J Clin Nutr. 92:436-443. Author weblink DOI.
- Fonville JM; Maher AD; Coen M; Holmes E; Lindon JC; Nicholson JK. (1 Mar 2010). Evaluation of full-resolution J-resolved 1H NMR projections of biofluids for metabonomics information retrieval and biomarker identification. Anal Chem. 82:1811-1821. Author weblink DOI.
- Clayton TA; Baker D; Lindon JC; Everett JR; Nicholson JK. (25 Aug 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. 106:14728-14733. Author weblink DOI.
- Holmes E; Loo RL; Stamler J; Bictash M; Yap IK; Chan Q; Ebbels T; De Iorio M; et alBrown IJ; Veselkov KA; Daviglus ML; Kesteloot H; Ueshima H; Zhao L; Nicholson JK; Elliott P. (15 May 2008). Human metabolic phenotype diversity and its association with diet and blood pressure. Nature. 453:396-400. Author weblink DOI.
- Li M; Wang B; Zhang M; Rantalainen M; Wang S; Zhou H; Zhang Y; Shen J; et alPang X; Zhang M; Wei H; Chen Y; Lu H; Zuo J; Su M; Qiu Y; Jia W; Xiao C; Smith LM; Yang S; Holmes E; Tang H; Zhao G; Nicholson JK; Li L; Zhao L. (12 Feb 2008). Symbiotic gut microbes modulate human metabolic phenotypes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 105:2117-2122. Author weblink DOI.
- Martin F-PJ; Wang Y; Sprenger N; Yap IKS; Lundstedt T; Lek P; Rezzi S; Ramadan Z; et alvan Bladeren P; Fay LB; Kochhar S; Lindon JC; Holmes E; Nicholson JK. (1 Jan 2008). Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. MOLECULAR SYSTEMS BIOLOGY. 4. Author weblink DOI.
- Claus SP; Tsang TM; Wang Y; Cloarec O; Skordi E; Martin FP; Rezzi S; Ross A; et alKochhar S; Holmes E; Nicholson JK. (Oct 2008). Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes. Molecular Systems Biology. 4.
- Martin F-PJ; Wang Y; Sprenger N; Yap IKS; Rezzi S; Ramadan Z; Pere-Trepat E; Rochat F; et alCherbut C; van Bladeren P; Fay LB; Kochhar S; Lindon JC; Holmes E; Nicholson JK. (1 Jul 2008). Top-down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model. MOLECULAR SYSTEMS BIOLOGY. 4. Author weblink DOI.
- Clayton TA; Lindon JC; Cloarec O; Antti H; Charuel C; Hanton G; Provost JP; Le Net JL; et alBaker D; Walley RJ; Everett JR; Nicholson JK. (20 Apr 2006). Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature. 440:1073-1077. Author weblink DOI.
- Nicholson JK; Holmes E; Wilson ID. (May 2005). Gut microorganisms, mammalian metabolism and personalized health care. Nat Rev Microbiol. 3:431-438. Author weblink DOI.
- Nicholson JK; Connelly J; Lindon JC; Holmes E. (Feb 2002). Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov. 1:153-161. Author weblink DOI.