A major emphasis in our group is directed towards understanding the mechanisms of neuroprotection by ischemic preconditioning (IPC) against cerebral ischemia (as elicited by a stroke or cardiac arrest). We have demonstrated in brain that IPC is mediated by two key signaling pathways. One of these pathways is a protein kinase C isozyme epsilon. Another signaling pathway involves the NAD+-dependent class III histone deacetylase SIRT1. Our laboratory is fully engaged in defining how these signaling pathways protect neurons against cell death. We are currently studying how these pathways alter synaptic plasticity and ameliorate mitochondrial function.
Another area of emphasis in our group is defining mechanisms by which some signaling pathways alter synaptic function following cardiac arrest. Cardiopulmonary arrest remains one of the leading causes of death and disability in the U.S.A. The chances of survival following cardiac arrest are poor, despite fast emergency responses and better techniques of defibrillation. Cardiac arrest with its consequent disruption of blood flow sets in motion a cascade of cellular derangements that result in brain damage.
A third area of emphasis in our group is the definition of the mechanisms of mitochondrial dysfunction following cerebral ischemia. It has been postulated that delayed cell death after brain ischemia may result from two different mechanisms: apoptosis and/or necrosis. In both pathways however, mitochondrial dysfunction appears to play a pivotal role. We are currently investigating the signaling pathways that lead to mitochondrial dysfunction following cerebral ischemia.