The brain is the most complex organ in the body and allows us to interact with the world around us.  Unlike many other tissues, neurons are not routinely or easily replaced.  When neurons are lost due to trauma or disease there is a significant loss of function.  In order to treat patients suffering neurologic dysfunction it will be necessary to accomplish several integrated goals including: (1) understanding the cellular death signaling pathways to reveal potential “drugable targets” for pharmaceutical intervention, (2) understanding endogenous survival pathways and learn how to induce these pathways to provide complimentary or alternative therapeutic targets, (3) to learn how nerves regenerate and find their appropriate targets, (4) to restore full function it may be necessary to replace the neurons that have been lost.
 
The research projects in my laboratory focus on these targets towards discovering new treatment strategies for neurologic injury with a focus on models of stroke and Parkinson’s disease.  Our Parkinson’s disease projects are focused on understanding how gene mutations result in disease.  To this end we use a combination of cell biology, protein biochemistry and genetically engineered animals.  Our neurotoxicity stroke model focuses on ischemic (loss of glucose and oxygen) and excitotoxic injury.  We have identified a highly choreographed signal cascade triggered by glutamate acting at the NMDA receptor, stimulating neuronal nitric oxide synthase that triggers lethal peroxynitrite generation and poly(ADP-ribose) polymerase activation.  We have recently described a new interaction between nuclear activation of poly(ADP-ribose) polymerase and mitochondrial release of apoptosis inducing factor, in the integration of the death signal.  In addition, we have gene discovery projects utilizing methods developed in the laboratory to understand which proteins are responsible for mediating the profound protection afforded to the brain by the phenomena of ‘preconditioning’.  We have found numerous new proteins whose function is not yet known that offer opportunities for discovery and identification of new therapeutic strategies to treat those who suffer the burden of brain disorders.