Alan R. Brash, Ph.D.
Professor, Department of Pharmacology
Research Description
The major focus of Alan Brash’s research is the mechanism of biosynthesis of oxygenated metabolites of essential fatty acids and their biological role. Unsaturated fatty acids are easily oxidized, and enzymes (fatty acid oxygenases) convert them to signaling molecules, including prostaglandins, leukotrienes, and other oxygenated lipids. A long-standing interest is how the enzymes (lipoxygenase, cyclooxygenase, and P450s) control the stereochemistry of these reactions. We are also unraveling the pathophysiology of two fatty acid oxygenases whose mutations cause disruption of the skin permeability barrier: the inactivating gene mutations result in ichthyosis (congenital scaly skin) in afflicted families, and neonatal lethality in mice. A further area of interest is metabolism of fatty acid peroxides by atypical cytochrome P450s and catalases, the latter a defense enzyme that normally metabolizes hydrogen peroxide. The Brash lab employs a wide variety of analytical methods: molecular cloning and expression of enzymes; synthesis of fatty acid analogs; structural analysis of novel substrates and enzymic products by HPLC, UV-Visible spectroscopy, GC-MS and LC-MS, and NMR.
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