During my career, I have been involved in various research topics. In my doctoral and early postdoctoral studies, my focus was primarily on protein folding in the endoplasmic reticulum, redox homeostasis in the cellular secretory pathway, the contribution of chaperone proteins, and a novel molecular mechanism associated with disulfide bond formation through the protein ERp44. This mechanism allows the formation of protein quaternary structures. The signaling mechanisms between ERp44 and its substrates were investigated in detail.
In the past 9 years, my primary focus has been on oncology, specifically addressing various themes:
- Metabolism of tumor cells: Tumor osteosarcoma cells exposed to microenvironmental acidity undergo significant biochemical and metabolic reprogramming, leading to the accumulation of lipid vesicles and overall alterations in cellular metabolism. The altered lipid metabolism, in turn, contributes to high tumorigenic potential.
- Tumor-stroma interaction: We observed a metabolic coupling between stromal cells and osteosarcoma cells. Specifically, lactate secretion by stromal cells activates biochemical and metabolic pathways leading to increased intracellular levels of citrate and acetyl-CoA, precursors of fatty acids and lipid vesicles essential for tumor survival in an acidic microenvironment.
- Microenvironmental acidity and the consequent lactate production have been the basis of my studies in recent years, with a particular focus on lipid metabolism and the metabolic shift from oxidative phosphorylation to glycolytic metabolism.
- 3D models: All our metabolic studies are conducted in 3D systems, considering that cellular behavior varies significantly when cultured in 2D or 3D. Recent studies have focused on 3D spheroids of osteosarcoma cells mixed with mesenchymal stromal cells in an acidic microenvironment, strongly influencing cellular metabolism.
- Molecular mechanisms of stress response: Microenvironmental acidity induces significant cellular stress and metabolic rewiring. Therefore, we are investigating the role of the Unfolded Protein Response, one of the most important cellular signaling pathways, in determining cell survival under conditions of severe environmental stress.
