José M Mato
jmmato
José M Mato
GENERAL DIRECTOR
IMI2 Programme
IMI2 Programme
General Director Office &
Precision Medicine and Metabolism Lab
Address: Bizkaia Science and Technology Park, building 801A, Derio (Bizkaia)
omillet
Óscar Millet
Group Leader

Precision Medicine and Metabolism Lab
Address: Bizkaia Science and Technology Park, building 800, Derio (Bizkaia)

José M Mato is founder and General Director of the Centers bioGUNE (Bilbao) and biomaGUNE (San Sebastián), and Research Professor of the Spanish National Research Council (CSIC), Spain. A graduate in Biochemistry at the Complutense University of Madrid, Professor Mato received a PhD degree from Leiden University and was awarded the CJ Kok prize for his thesis. He was a postdoctoral fellow at the Biozentrum of the University of Basel and the National Institutes of Health, and a faculty member at the Jiménez Díaz Foundation in Madrid before been named Research Professor at the CSIC. He has been Professor of the Faculty of Medicine of the University of Navarra and Visiting Professor at the University of Pennsylvania and Thomas Jeff erson University. From 1992 to 1996 Professor Mato was President of the CSIC and in 2004 was awarded the Spanish National Research Prize in Medicine.

Latest Publications

2023

2022

The Precision Medicine and Metabolism Laboratory is dedicated to advancing precision medicine through a detailed study of metabolism. Utilizing cutting-edge techniques such as NMR-based metabolomics, the laboratory analyzes extensive cohorts of urine and serum samples, enabling the examination of metabolic profiles across more than 10,000 individuals. This comprehensive approach aims to enhance the understanding of population-level metabolism and ultimately develop personalized medical treatments that are more effective and tailored to individual metabolic profiles.

In addition to its focus on precision medicine, the laboratory is deeply involved in investigating metabolism and liver diseases. The team employs advanced methods, including metabolomics and molecular biology, to unravel the molecular mechanisms underlying metabolic disorders and liver conditions, with the goal of identifying potential therapeutic strategies. Collaborating with local, national, and international institutions, the lab strives to drive innovation and scientific discovery, contributing to both the scientific community and public health by developing new diagnostic methods and advanced therapies. Our laboratory is currently exploring the following topics:

Research line 1: Metabolism
Metabolism describes the chemical reactions involved in maintaining the living state of the cells and the organism. In our laboratory, we are interested in the metabolic pathways that result in liver disease when ill-functioning and the biosynthetic pathway of the heme group. To that end, we use a combination of cellular, biochemical and biophysical techniques and, most specially, NMR spectroscopy. For instance, we have recently developed a methodology to describe the metabolism in a nutshell by using 31P-NMR spectroscopy.

Research line 2: Metabolomics
Metabolomics is the large-scale study of small molecules, commonly known as metabolites, within cells, biofluids, tissues or organisms. In our laboratory, we employ NMR-based metabolomics (methodology and applications) of urine and serum samples, targeting large cohorts (i. e. > 10.000 individuals). The final goal is to describe the population at the metabolic level and advance towards a precision medicine program within the region. To that end, we have a fully equipped laboratory including two IVDr 600 MHz spectrometers and a SamplePro robot.

Research line 3: Metabolomic rare diseases
Rare diseases (~7000 identified to date) are an area of significant medical need affecting an estimated 350 million people worldwide, with ~95% having no currently approved drug treatment. They are often produced by inherited mutations affecting the activity of a protein and it is becoming increasingly evident that, most frequently, a mutation destabilizes the protein/enzyme, ultimately affecting its intracellular homeostasis. In this context, pharmacological chaperones (small molecules which bind to the protein, restoring stability and activity without affecting its function) can be applied to many diseases. Inherited metabolic disorders represent a heterogeneous collection of genetic diseases caused by rare mutations that affect the function of individual proteins. In our laboratory we are interested in using NMR spectroscopy for the early detection of inborn errors of metabolism and to explore the mechanism and therapeutic intervention in two metabolic rare diseases: congenital erythropoietic porphyria, a disorder of the heme biosynthetic pathway and tyrosinemia type I, a disease related to the accumulation of tyrosine by-products. To that end, we make use of a plethora of techniques including CRISPR/Cas9, specific animal models and in-house designed NMR-based metabolic and fluxomic experiments.

Research line 4: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Our research emphasizes the use of metabolomics and lipidomics to identify biomarkers and develop non-invasive diagnostic tests for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The laboratory's work aims to understand the metabolic pathways and molecular mechanisms underlying liver diseases, which is critical for developing new therapeutic strategies and improving patient outcomes.

Research line 5: Protein stability
Protein stability (thermodynamic and kinetic) drives the biophysical properties of the polypeptide chain (protein folding) and the protein's concentration in the cellular environment (protein homeostasis). It is the result of a delicate balance between inter- and intramolecular interactions, which can be easily altered by mutations and/or upon changes in the composition of the surrounding media. In this context, NMR spectroscopy offers a plethora of suitable experiments to investigate protein stability.

Collaborations
Jeremy Nicholson & Julien Wist (Murdoch University). Ulrich Guenther (Lubeck University). Simon Mallal & Markus Voehler (Vanderbilt University). Gary Frost & Elaine Holmes (Imperial College). Manfred Spraul & Harmut Schaeffer (Bruker). Quentin Anstee (Newcastle University). Shelly Lu & Mazen Nouredin (Cedars Sinai). Quentin Anstee (Newcastle University). Toni Vidal (Cambridge University). Luca Valenti (University of Milan). Keneth Cusi (University of Florida). Nicholas Davidson (Washington University). Marco Arrese (Univ. Católica de Chile). Scott Friedman (Mount sinai). Arun Sanyal (Virginia University). Robert Desnick (Mount Sinai). Emmanuel Richard & Jean Marc Blouin (Université de Bordeaux). Dolores Corella (Universitat de Valencia). Eduardo Anguita (Hospital Clínico San Carlos). Juan Arriaga (Hospital de Basurto). Pedro España (Hospital de Galdakao). Miguel Ángel Morán (Hospital de Txagorritxu). Maria Luisa Seco (Osarten). Rubén Nogueiras & Miguel López (CIMUS). Beatriz Macías (Universidad de Extremadura). Jesús Bañales (Biodonostia). Antonio Martín-Duce (Hospital Príncipe de Asturias). Manuel Romero (Hospital Valme).

Links
https://www.omilletlab.com/

Latest Publications

Genetic algorithms applied to translational strategy in metabolic-dysfunction associated steatohepatitis (MASH). Learning from mouse models

Martínez-Arranz, I; Alonso, C; Mayo, R; Mincholé, I; Mato, JM; Lee, DJ;

COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE

2024-10-01

The role of forkhead box M1-methionine adenosyltransferase 2A/2B axis in liver inflammation and fibrosis.

Yang, Bing; Lu, Liqing; Xiong, Ting; Fan, Wei; Wang, Jiaohong; Barbier-Torres, Lucia; Chhimwal, Jyoti; Sinha, Sonal; Tsuchiya, Takashi; Mavila, Nirmala; Tomasi, Maria Lauda; Cao, DuoYao; Zhang, ...

Nature communications

2024-09-27

Letter to the Editor: Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF)

Noureddin, M; Truong, E; Mayo, R; Martínez-Arranz, I; Mincholé, I; Banales, JM; Arrese, M; Cusi, K; Arias-Loste, MT; Bruha, R; Romero-Gómez, M; Iruzubieta, P; Aller, R; Ampuero, J; Calleja, ...

HEPATOLOGY

2024-09-26

Pseudophosphorylation of single residues of the J-domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system

Velasco-Carneros, L; Bernardo-Seisdedos, G; Maréchal, JD; Millet, O; Moro, F; Muga, A;

PROTEIN SCIENCE

2024-08-01

MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics

Gil-Redondo, R; Conde, R; Bruzzone, C; Seco, ML; Bizkarguenaga, M; González-Valle, B; de Diego, A; Lain, A; Habisch, H; Haudum, C; Verheyen, N; Obermayer-Pietsch, B; Margarita, S; Pelusi, S; ...

CARDIOVASCULAR DIABETOLOGY

2024-07-24

Seroprevalence of adeno-associated virus types 1, 2, 3, 4, 5, 6, 8, and 9 in a Basque cohort of healthy donors

Navarro-Oliveros, M; Vidaurrazaga, A; Guerra, GS; Castellana, D; Embade, N; Millet, O; Marigorta, UM; Abrescia, NGA;

SCIENTIFIC REPORTS

2024-07-10

Preovulatory follicular fluid secretome added to in vitro maturation medium influences the metabolism of equine cumulus-oocyte complexes

Luis-Calero, M; Ortiz-Rodríguez, JM; Fernández-Hernández, P; Muñoz-García, CC; Pericuesta, E; Gutiérrez-Adán, A; Marinaro, F; Embade, N; Conde, R; Bizkarguenaga, M; Millet, O; González-Fernández, ...

BMC VETERINARY RESEARCH

2024-06-25

Electrostatics introduce a trade-off between mesophilic stability and adaptation in halophilic proteins

Herrero-Alfonso, P; Pejenaute, A; Millet, O; Ortega-Quintanilla, G;

PROTEIN SCIENCE

2024-06-01

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)

Vacca, M; Kamzolas, I; Harder, LM; Oakley, F; Trautwein, C; Hatting, M; Ross, T; Bernardo, B; Oldenburger, A; Hjuler, ST; Ksiazek, I; Lindén, D; Schuppan, D; Rodriguez-Cuenca, S; Tonini, MM; ...

NATURE METABOLISM

2024-06-01

Congenital erythropoietic porphyria

To-Figueras, J; Erwin, AL; Aguilera, P; Millet, O; Desnick, RJ;

LIVER INTERNATIONAL

2024-05-08

Stratification of Sepsis Patients on Admission into the Intensive Care Unit According to Differential Plasma Metabolic Phenotypes

Lodge, S; Litton, E; Gray, N; Ryan, M; Millet, O; Fear, M; Raby, E; Currie, A; Wood, F; Holmes, E; Wist, J; Nicholson, JK;

JOURNAL OF PROTEOME RESEARCH

2024-03-21

Cross-Validation of Metabolic Phenotypes in SARS-CoV-2 Infected Subpopulations Using Targeted Liquid Chromatography-Mass Spectrometry (LC-MS)

Whiley, L; Lawler, NG; Zeng, AX; Lee, A; Chin, ST; Bizkarguenaga, M; Bruzzone, C; Embade, N; Wist, J; Holmes, E; Millet, O; Nicholson, JK; Gray, N;

JOURNAL OF PROTEOME RESEARCH

2024-03-14

Characterization of preovulatory follicular fluid secretome and its effects on equine oocytes during in vitro maturation

Luis-Calero, M; Marinaro, F; Fernández-Hernández, P; Ortiz-Rodríguez, JM; Casado, JG; Pericuesta, E; Gutiérrez-Adán, A; González, E; Azkargorta, M; Conde, R; Bizkarguenaga, M; Embade, N; Elortza, ...

RESEARCH IN VETERINARY SCIENCE

2024-03-11

Impaired Hepatic Very Low-Density Lipoprotein Secretion Promotes Tumorigenesis and Is Accelerated with Fabp1 Deletion

Newberry, EP; Molitor, EA; Liu, AL; Chong, KMY; Liu, XL; Alonso, C; Mato, JM; Davidson, NO;

AMERICAN JOURNAL OF PATHOLOGY

2024-02-28

Serum and Urine Metabolomic Profiling of Newly Diagnosed Treatment-Naive Inflammatory Bowel Disease Patients

Aldars-García, L; Gil-Redondo, R; Embade, N; Riestra, S; Rivero, M; Gutiérrez, A; Rodríguez-Lago, I; Fernández-Salazar, L; Ceballos, D; Benitez, JM; Aguas, M; Baston-Rey, I; Bermejo, F; Casanova, ...

INFLAMMATORY BOWEL DISEASES

2024-02-01

Quantitative Analysis of the Human Semen Phosphorometabolome by 31P-NMR

Serrano, R; Martin-Hidalgo, D; Bilbao, J; Bernardo-Seisdedos, G; Millet, O; Garcia-Marin, LJ; Bragado, MJ;

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

2024-02-01

Effect of age and dietary habits on Red Blood Cell membrane fatty acids in a Southern Europe population (Basque Country)

Marrugat, G; Cano, A; Amézaga, J; Arranz, S; Embade, N; Millet, O; Ferreri, C; Tueros, I;

PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS

2024-01-01

Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF)

Noureddin, M; Truong, E; Mayo, R; Martínez-Arranz, I; Banales, JM; Mincholé, I; Arrese, M; Cusi, K; Arias-Loste, MT; Bruha, R; Romero-Gómez, M; Iruzubieta, P; Aller, R; Ampuero, J; Calleja, ...

HEPATOLOGY

2024-01-01

S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver

Barbier-Torres, L; Chhimwal, J; Kim, SY; Ramani, K; Robinson, A; Yang, HP; Van Eyk, J; Liangpunsakul, S; Seki, E; Mato, JM; Lu, SC;

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES

2024-01-01

Dysfunctional VLDL metabolism in MASLD.

Marigorta, Urko M; Millet, Oscar; Lu, Shelly C; Mato, Jose M;

NPJ metabolic health and disease

2024-01-01