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