87% of stroke cases are ischemic and a common cause is the rupture of an atherosclerotic plaque. Atherosclerotic plaque is a deposit of fat and cellular material on the vessel wall that can rupture and cause thromboembolic complications. When a plaque shows an increased risk of rupture, it is defined as vulnerable. Diagnostic tests commonly conducted on atherosclerotic patients, such as Doppler ultrasound, do not clearly identify vulnerable plaques. The complement system is an inflammatory process involved in the morphological evolution of the plaque. Our laboratory’s work aims to identify circulating biomarkers of the complement system that can predict plaque vulnerability and the risk of ischemic stroke. In particular, we have observed that high levels of certain initiating proteins of the lectin pathway of complement, called collectins, are associated with the presence of a vulnerable plaque in patients. Our work is dedicated to validating complement biomarkers, identifying active complement products with the highest predictive sensitivity, and understanding the inflammatory mechanisms within the plaque associated with these identified molecules. The availability of a circulating marker for plaque vulnerability would improve the early identification and treatment of ischemic risk patients.

Alpha-synuclein (αSyn) is a protein crucial for various cellular functions, such as the regulation of neurotransmitter release and modulation of communication between neurons. Although it is mainly known for its involvement in neurodegenerative diseases like Parkinson's disease, its role is emerging in post-ischemic brain damage. The research project aims to investigate αSyn’s contribution to brain damage resulting from ischemia and vascular recovery. To achieve this, we will investigate whether the absence of aSyn alleviates microvascular dysfunction following primary acute damage and if this is associated with the accumulation of extracellular toxic forms of αSyn. The ultimate goal of the project is to propose αSyn as a therapeutic target in the post-acute phase of ischemic stroke, where treatment options are limited.

Wiskott-Aldrich Syndrome (WAS) is a rare genetic disorder caused by a deficiency of the WAS protein, an important regulator of immune cell development. The most common clinical manifestations are autoimmune diseases and bleeding, but neurological manifestations may also occur. The mechanisms responsible for neurological events are poorly understood, but it is hypothesized that resident immune cells, such as microglia, may be involved. The WAS gene is constitutively expressed by microglia. Microglia plays a physiological role in continuous surveillance of brain homeostasis and participates in synaptic remodeling during development, which underpins the formation of the neural network. In pathological conditions, its activation and dysregulation can directly contribute to neurological damage. The project aims to investigate: 1) whether WAS is implicated in the physiological processes of brain development coordinated by microglia; 2) whether WAS deficiency induces specific neurological consequences associated with behavioral alterations. Among the proposed experimental models, the project includes the use of reprogrammed pluripotent stem cells (iPSCs), which will be induced to mature into brain cell populations. This technology will enable future precision pharmacological studies based on peripheral cells non-invasively obtained from patients themselves. The ultimate goal is to identify potential pharmacological targets to limit the neurological consequences associated with Wiskott-Aldrich Syndrome and improve the life expectancy of affected patients. Nel Laboratorio di Ricerca sul Danno Cerebrale e Cardiovascolare acuto progettiamo, coordiniamo ed eseguiamo studi clinici multicentrici randomizzati e controllati per valutare l'efficacia di trattamenti innovativi nella medicina d'urgenza e nelle malattie cardiovascolari. Questi studi vengono utilizzati per raccogliere campioni di sangue e tessuti in una biobanca certificata. L'obiettivo principale del laboratorio, utilizzando la biobanca, è identificare i biomarcatori presenti nel sangue, che forniscono informazioni sulla gravità e sulla progressione della malattia, contribuendo così allo sviluppo di trattamenti personalizzati e più efficaci.