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My research involves the structure and mechanism of action of monooxygenase systems, especially those involved in metabolism of neurotransmitter and hormone signals. This fundamental research has direct medical relevance as aberrant behavior of oxygen utilizing enzymes has been implicated to varying degrees in many neurodegenerative diseases including Amyotrophic Lateral Sclerosis (Lou Gehrig's disease), Parkinson's disease, and Alzheimer's disease. To study these enzymes my laboratory employs organic synthesis to produce enzyme inhibitors, biochemistry to measure the effects of the inhibitors and probe enzyme mechanism, molecular biology to probe the effects of changes in protein sequence on enzyme properties, and spectroscopy and crystallography to study the structure and physical properties of the enzymes. In addition to using small molecules to study enzymes, we also use enzymes to synthesize and study interesting small molecules on a research (200 mg) scale. Ongoing projects in the lab include the characterization of CYP46, a cyt. P450 that hydroxylates cholesterol prior to its removal from the brain. CYP46 has recently been linked to Alzheimer's Disease. Other projects include characterization of novel bacterial model P450 systems involved in the biosynthesis of natural anti-cancer agents and cancer promoting mycotoxins.
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