1. Pulmonary Arterial Hypertension (PAH) and the Kynurenine Pathway
- Our work focuses on elucidating the metabolic changes associated with PAH development. Studies highlight the role of the kynurenine pathway in PAH pathogenesis and its correlation with disease progression, pulmonary vascular changes, and right ventricular dysfunction.
- Notably, we have shown that an increased kynurenine-to-tryptophan (kyn/trp) ratio precedes clinical PAH diagnosis in systemic sclerosis patients, making it a potential early biomarker.
2. Biomarker Discovery in Neonatal and Pediatric Conditions
- In neonatal encephalopathy (NE), our research has identified plasma metabolites associated with long-term neurodevelopmental outcomes. This work has provided novel insights into amino acid pathways (e.g., arginine, histidine) and their predictive value in clinical models.
- In neonatal cardiac surgery, our metabolomics studies revealed perioperative metabolic profiles associated with adverse outcomes such as cardiac injury, acute kidney injury, and mortality. This work has implications for improving perioperative care.
3. Amino Acid Metabolism
- In PAH, our studies revealed significant shifts in amino acid metabolism across the pulmonary vasculature. For example, branched-chain amino acids (BCAAs) were found to be decreased in circulation but increased intracellularly in pulmonary endothelial cells, reflecting metabolic dysregulation.
- We also explored the metabolic profiles of human milk, showing that D-amino acids are present in preterm milk and decrease as lactation progresses. This study underscores the potential nutritional and regulatory roles of amino acid enantiomers.
4. Integration of Metabolomics in Disease Pathophysiology
- In Type 2 Diabetes, we applied metabolomics to study the effect of intensive lifestyle interventions on sex hormones. This work demonstrated how weight loss influences estradiol, testosterone, and sex hormone-binding globulin differently in men and women, linking metabolic changes to broader health risks.
5. Advanced Analytical and Methodological Expertise
- Across our studies, we employed targeted and untargeted metabolomics using high-resolution LC-MS/MS, enabling the identification and quantification of a broad spectrum of metabolites.
- Our ability to integrate metabolomics with clinical, genetic, and physiological data has helped elucidate complex disease mechanisms and identify novel therapeutic targets.
6. Translational and Clinical Relevance
- We have significantly contributed to understanding metabolic pathways' role in health and disease, with applications ranging from biomarker discovery to potential therapeutic targets. For example:
- The kynurenine pathway was identified as a modifiable target in PAH, with implications for early diagnosis and intervention.
- Perioperative metabolic markers in neonates were shown to improve risk stratification, providing a foundation for tailored treatment.
7. Collaborative and Interdisciplinary Research
- Our bibliography reflects contributions across multiple teams and disease areas, including cardiovascular, neonatal, and neurological research. This showcases our ability to collaborate effectively and integrate metabolomics into diverse fields.