The activity of the Research Laboratory on Applied Metabolomics (LIMA) can be divided in two main research lines.
Development and application of metabolomic approaches for detection of biomarkers in different pathological conditions.
The main goals of this research line are (i) the development of appropriate analytical methodologies for the detection of changes produced in targeted metabolic pathways and (ii) their application to several fields related with health and disease. Regarding the applied strategy, this line is divided in:
1.- Targeted metabolomics. LIMA is specialized in the development and application of targeted metabolomics approaches. We have developed analytical strategies for the quantitative determination of key metabolic pathways such as:
- Steroidogenesis: Involved in several physiological processes. A large part of LIMA activity is related with steroids. We have developed analytical methods for the determination fo the steroid profile in several matrices such as urine, plasma, saliva, hair, breast milk or amniotic fluid.
- Monoamine neurotransmitters: Involved in several processes related with the central nervous system. LIMA has developed analytical approaches for the determination of these compounds including serotonin, dopamine and noradrenaline y urine, blood or brain.
- Polar Neurotransmitters: Involved in key processes of the central nervious system, the mass spectrometric determination of these analytes remains an analytical challenge. LIMA has developed analytical approaches for the quantification of these analytes (including GABA, glutamate, glutamine and acetylcholine) in plasma, brain and urine.
- Endocannabinoids: natural ligands of cannabinoid receptors and modulators of a number of physiological functions. LIMA has developed analytical approaches for the determination of these compounds including 2-AG and 2-AEA in blood or brain.
- Kynurenine pathway: Involved in inflammation processes and potentially related with pathological statuses such as depression and neurodegenerative disorders. LIMA has developed analytical methodology for the determination of these compounds in urine, plasma and brain
- Tricarboxylic Acids Cycle (Krebs Cycle): Metabolic cycle involved in energetic production. It is altered in several pathological conditions. LIMA has developed analytical methodology for the determination of these compounds in urine, plasma, liver, brain or formalin-fixed paraffin-embedded (FFPE) tissues.
- Lipidomics: Includes the study of multiple lipid families, which are not only building blocks of cell membranes and have energy storage functions, but they play also an increasingly key role as bioactive molecules. The LIMA is developing new targeted lipidomics methods and currently has the methodology to measure ceramides, hexosylceramides, diacylglycerols, monoacylglycerols, free fatty acids, lysophosphatidylcholines and sphingomyelins in different biological matrices (plasma, serum, liver, brain and cell cultures).
- Glycolysis: Involved in energetic production. Their mass spectrometric determination remains an analytical challenge due to the physico-chemical characteristics of the analytes. LIMA is developing analytical methodologies for the determination of these compounds in several matrices.
- ATP/ADP and other phosphorylated compounds: Responsible of the energetic generation and storage. LIMA is developing an analytical approach for their determination together with other phosphorylated compounds (thiamine, AMP) in different matrices.
One of the main goals of this research line is to transfer these approaches for their application in several pathological conditions. Currently, we have applied them to several fields including acute intermittent porphyria, light at night exposition, prediction of the effect of new psychoactive substances, effect of maternal separation, fetal growth restriction or prenatal diagnosis.
2.- Although most of the LIMA activity is focused on targeted metabolomics, we have also experience in untargeted metabolomics. LIMA has applied this experience to several fields including acute intermittent porphyria, prenatal diagnosis or the fight against doping.
Elucidation of alternative conjugation and evaluation of their clinical relevance.
The main goal of this research line is the characterization of conjugate metabolites and the determination of their clinical relevance. Currently, we have detected several conjugates previously unreported or underestimated such as:
- Progestogens conjugated with cysteine. We have detected for the first time the occurrence of that group of compounds. We have confirmed their adrenal origin. We are currently evaluating their potential as marker for antioxidant status.
- Steroids conjugated as bis-sulfates. We have developed a method for the open detection of this understudied class of metabolites. We have confirmed their presence in urine and plasma. We have postulated them as markers for several diseases related with the steroidogenesis.
- Monoamines conjugated with succinic acid. We have detected for the first time the conjugation of monoamines with succinic acid. We are currently exploring the potential of endogenous monoamines to form these conjugates and their implication in changes on brain neurotransmitters levels.
