My research focuses on the molecular mechanisms regulating cholesterol metabolism and inflammatory signalling, and on their dysregulation in neurodegenerative, cardiovascular, autoimmune, and infectious diseases. The overarching goal is to elucidate the interplay between lipid homeostasis and inflammation and to identify novel pharmacological and nutraceutical strategies capable of modulating these pathological processes. Current research activity is organised into three main areas:
1. In vitro studies on cholesterol metabolism and inflammatory pathways. This research investigates the molecular mechanisms governing intracellular cholesterol homeostasis and their alterations under pathological conditions. Particular attention is devoted to the regulation of lipoprotein receptors and transporters, cholesterol synthesis, uptake and efflux, as well as intracellular cholesterol trafficking and plasma membrane distribution. A major research focus is the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the regulation of brain cholesterol metabolism and neuroinflammation. Ongoing studies aim to characterize the molecular mechanisms linking PCSK9 to lipid homeostasis and inflammatory signalling pathways and to identify innovative lipid-based therapeutic targets for Alzheimer's disease and other neurodegenerative disorders. More recently, this research has expanded to investigate cholesterol metabolism and inflammatory responses in vascular ageing, as well as host lipid metabolism during viral infections, with the objective of identifying host-directed antiviral therapeutic strategies.
2. Ex vivo functional studies of lipoproteins in human biological fluids. This research evaluates the functional properties of lipoproteins isolated from cerebrospinal fluid and serum of patients with neurodegenerative diseases (including Alzheimer's disease) and populations at increased cardiovascular risk, such as patients with rheumatoid arthritis. Studies focus on assessing the capacity of cerebrospinal fluid HDL particles to promote cholesterol efflux from human astrocytes, a key process for maintaining neuronal cholesterol homeostasis. In parallel, serum HDL functionality is investigated through the evaluation of cholesterol efflux capacity (CEC), the first and rate-limiting step of reverse cholesterol transport, together with serum cholesterol loading capacity (CLC), which reflects the ability of circulating lipoproteins to induce intracellular cholesterol accumulation. Additional investigations examine qualitative changes in HDL particles, including their enrichment with serum amyloid A (SAA) and the activity of the HDL-associated antioxidant enzyme paraoxonase-1 (PON1), as biomarkers of impaired anti-inflammatory and antioxidant functions.
3. Ex vivo characterisation of inflammatory and lipid biomarkers. Research in this area employs human and murine biological samples, including serum and tissue biopsies (brain, liver, adipose tissue, and vascular tissue), to characterise lipid metabolism, immune activation, and inflammatory responses. Current studies also investigate macrophage polarization, cellular senescence, activation of innate immune pathways, and inflammatory mediators associated with chronic diseases. In parallel, advanced biochemical and molecular approaches are used to isolate and quantify lipid species, lipoprotein-associated proteins, and inflammatory biomarkers, with the aim of identifying novel mechanistic insights and translational biomarkers relevant to disease progression and therapeutic response.
