Thomas J. Montine, MD, PhD
Professor, Department of Pathology
Research in this laboratory focuses on mechanisms of disease and therapeutic targets in age-related neurodegeneration. Our basic premise is that production of molecules that are injurious to brain accompanies advancing age and certain diseases, such as Parkinson’s disease and Alzheimer’s disease. Our goals are to understand the means of production and inactivation of endogenous neurotoxins, and in doing so discover new methods for halting or slowing the progression of these neurodegenerative diseases. Currently our efforts are focused in three areas. The first are oxygenated lipids, such as eicosanoids, that are generated to excess in diseased regions of brain in patients with Alzheimer’s disease. Our work has shown that some of these lipids modify the innate immune response in cerebrum, potently destabilize the neuronal cytoskeleton, and enhance excitotoxic neurodegeneration. Another class of molecules, called catechol thioethers, is produced in diseased regions of brain in patients with Parkinson’s disease. These molecules are neurotoxic in experimental models, and our current efforts are attempting to determine their contribution to the progression of Parkinson’s disease. Finally, we are using proteomic techniques to pursue the mechanisms by which inheritance of the epsilon 2 allele of APOE is neuroprotective from a variety of insults. Techniques used in the Montine laboratory include analytical biochemistry with a variety of chromatographic and mass spectrometric detection methods, protein biochemistry and proteomics, and molecular biology. Our models include, in vitro, cell and tissue culture, and transgenic mice as well as evaluation of tissue obtained from patients participating in clinical trials.