William Dean Matthew
Adjunct Professor in the Department of Neurology
Dr. Matthew's research is targeted at improving recovery from neural injury and slowing the progression of neurodegenerative diseases. A central goal in his work is to understand how injured neural cells respond to growth factors within a complex in vivo environment, where multiple molecular cues may potentiate or antagonize growth factor function. Apolipoprotein E (apoE), which is traditionally defined as a cholesterol trafficking protein, has recently been shown to play a variety of protective functions after neural trauma. The expression of apoE is increased many-fold following acute or chronic neural injuries and during development. Experiments in Dr. Matthew's lab have led to the hypothesis that apoE can modulate growth factor activities; in some experimental conditions apoE potentiates biological activities (namely neurotrophic factors) and in other paradigms apoE suppresses factors (for instance, proinflammatory cytokines). Understanding the function of apoE after injury has significant clinical relevance in the nervous system and other organs as well. There are three human alleles of APOE - E2, E3 and E4, which differ at two amino acid sites. The inheritance of APOE4 is associated with an increased incidence of Alzheimer's Disease and poor recovery from neural injuries. Also, as a major secretory product of macrophage, apoE is likely to play a role in recovery from all tissue injuries. Current experiments are exploring the mechanism by which apoE modulates the biologic effects of growth factors. Through an understanding of how apoE isoforms are neuroprotective, one can anticipate strategies to protect against neural degeneration after injury, to slow the progression of neurodegenerative diseases, and to facilitate neural regeneration and tissue repair.
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