Research Projects

Neutrophils have evolved as true sentinel cells for detecting sites of tissue damage, act as effectors of innate immune system and provide pivotal contribution to the acute inflammatory response. Apart from their role on invading pathogens, recent studies have demonstrated that neutrophils are versatile cells, capable of regulating various biological processes associated with the tissue microenvironment thus impacting both human health and disease. Although 70% of acute strokes are ischemic strokes, their underlying pathophysiological role is not fully understood. Role of neuronal and endothelial acute inflammation is even less understood. Dysregulated immune function of neutrophils due to immunosenescence, contribute to the increased susceptibility of the elderly to events leading stroke. Immunosenescence may control how the neutrophils activate, release cytokines, undergo Netosis and influence/interact with the endothelial cells during ischemic stroke. Since neutrophils already express deregulated cell-cycle proteins (CDK4/CDK8, p21, p27, p53 and etc.) leading to their cell-cycle arrest, understanding of setting of senescence disturbing their innate immunity function is critical. Simultaneously, impact of senescing neutrophils on the endothelial cells in the plaque milieu as these endothelial cells also control interaction with platelets, undertake elastic and contractile function through the expression of cell-surface and cytoskeletal proteins. Therefore, to address questions of influence of neutrophils on intra-arterial plaques that leads to occlusion and impact on the microenvironment of endothelial cells, we formulated following objectives: 1. isolate and characterize neutrophils to identify immunosenescence and cell cycle markers in band and mature stages. 2. evaluate the Neutrophil-Endothelial Axis During Inflammation and Immunosenescence in co-culture models and 3. investigate therapeutic strategies targeting neutrophil senescence in ischemic in-vivo model. We believe that our investigations will unravel mechanisms of immunosenescence due to disturbed immunohaemostasis during ischemic stroke and will unravel new targets for using senolytic agents.