FOCUSOur laboratory studies ways in which the brain protects itself from and repairs injury, especially injury due to stroke or neurodegeneration. We investigate both molecular and cellular mechanisms. The underlying premise is that we may be able to adapt the brain's own protection and repair strategies to design new treatments for neurological disease. Current projects are summarized below. CURRENT RESEARCH PROJECTSNew Gene Expression in Cell Culture Models of Ischemia Primary neuronal cell culture models are used to investigate the neurocidal or neuroprotective effects of gene products whose expression is altered by cerebral ischemia. The long-term objective is to identify endogenous mechanisms of neuronal death and neuroprotection that can be exploited in the treatment of stroke. VEGF in Neuroprotection and Neurogenesis Vascular endothelial growth factor (VEGF or VEGF-A) is a hypoxia-inducible secreted protein that interacts with receptor tyrosine kinases on endothelial cells to promote angiogenesis. VEGF also acts directly on neurons to produce neurotrophic and neuroprotective effects, and on neuronal precursor cells in the adult brain to stimulate neurogenesis. The goal of this work is to understand how VEGF affects neurons and their cellular precursors, and to identify possible therapeutic roles for VEGF in stroke and other neurological disorders. Cannabinoids and Neuroprotection Endogenous cannabinoid (endocannabinoid) signaling pathways have been implicated in normal brain functions, such as adult neurogenesis, as well as in neuroprotection following cerebral ischemia. We hypothesize that these roles can be exploited to design new treatments for stroke and neurodegenerative disease. Injury-Induced Neurogenesis Acute and chronic neurodegenerative disorders stimulate the production of new neurons (neurogenesis) in the adult brain. However, the principles that govern injury-induced neurogenesis are poorly understood. We hypothesize that identifiable features of injury in the adult brain determine whether and where the injury will stimulate neurogenesis, and regulate the phenotypic and geographic fate of the new neurons that are produced. Our long-term goal is to achieve a better understanding of the biological mechanisms involved in injury-induced neurogenesis, so they can be manipulated for therapeutic purposes. Neuroglobin and Neuroprotection We are studying the cytoprotective properties of neuroglobin, a protein expressed primarily in neurons and induced by hypoxia or ischemia. We have produced a neuroglobin-overexpressing transgenic mouse and are characterizing its phenotype, as well as crossing it with transgenic mouse models of neurodegenerative disease. The aim is to determine how neuroglobin exerts its neuroprotective effect and whether therapeutic induction of neuroglobin expression might be possible.
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