Research Projects

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, often leading to systemic inflammation and multiorgan failure. A key consequence of this inflammatory dysregulation is the disruption of the body’s natural hemostatic balance, resulting in an increased risk of thrombotic and thromboembolic complications such as myocardial infarction, venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC), which are major contributors to sepsis-associated mortality. We hypothesized that during sepsis, heightened inflammatory signalling leads to reactive oxygen species (ROS) bursts in both neutrophils and platelets, promoting mitochondrial damage, release of mtDNA and also fosters the formation of platelet aggregation and platelet–neutrophil aggregates leading to enhanced NETosis and increased thrombotic events. Platelets actively participate in immune responses and promote NETosis through direct interaction with neutrophils NETs are web-like structures composed of cell-free DNA, histones, and granule proteins, which are inherently prothrombotic in nature and contribute to microvascular thrombosis. Elevated NET levels in sepsis patients have been associated with higher thrombotic burden and worse clinical outcomes. We will use Cecal Ligation and Puncture (CLP) mouse modelling sepsis condition, which closely mimics human polymicrobial sepsis, offers an ideal system to experimentally probe these mechanisms alongside patient-derived plasma and cellular assays. Given these interconnected mechanisms, identifying molecular signatures associated with NETosis and mitochondrial dysfunction may provide valuable diagnostic biomarkers for thrombotic complications in sepsis. Therefore, this proposal aims to identify and characterize diagnostic molecule associated with thrombotic or thromboembolic complications in sepsis patients with a particular focus on the role of dysregulated mitochondrial function in platelets and neutrophils. This could pave the way for early detection and improved therapeutic strategies to reduce thrombotic and thromboembolic burden and mortality in septic patients. Novelty: This study will provide the early diagnostic marker and mechanism-based strategy to reduce the thrombotic complications in sepsis patients.