Research Summary
Dr. Wood's laboratory is studying cholesterol regulation in brain, the role of cholesterol in cell structure and function, its involvement in neurodegenerative diseases, and mechanisms of neuroprotection afforded by cholesterol lowering drugs. Cholesterol plays many roles in brain and it is required for optimal functioning. As with cholesterol outside of brain, regulation of this molecule in brain can go awry as demonstrated most pointedly in human malformation syndromes of inborn errors of cholesterol synthesis and Niemann-Pick type C disease. Furthermore, there is evidence suggestive of cholesterol being a factor in neurodegenerative diseases such as Huntington's disease, Alzheimer's disease, and pathophysiology occurring with increasing age. Dr. Wood's group uses several different approaches (e.g., molecular and cellular biology, transgenic animal and cell lines) in understanding dynamics of brain cholesterol. There are two major projects in the Wood lab. One project is examining how the Golgi complex in astrocytes regulates cholesterol trafficking, modulation by a protein thought to be a culprit in Alzheimer's disease and consequences of such actions on neuronal structure and function in brain cells of mice expressing human apolipoproteins 2, 3, and 4. Apolipoprotein E4 is a risk factor for Alzheimer's disease. The second project is focused on understanding the mechanisms whereby statins (cholesterol lowering drugs) afford neuroprotection to brain cells. The lab has recently made the novel discovery that statins both in vivo and in vitro stimulate gene expression and protein levels of one of the foremost anti-apoptotic molecules, Bcl-2. Currently, studies are focused on mechanisms of statin-induction of Bcl-2.