Total Synthesis

Phosphatase Activity Modulators: We are currently interested in natural products that interact with the serine-threonine protein phosphatases PP1 and PP2A. Protein phosphatases catalyze the removal of phosphates from amino acid residues in proteins. These enzymes, along with kinases, regulate certain cellular signaling pathways. The proper modulation of protein phosphatase activity is central to the study of these cell signaling pathways and to the development of new therapeutic compounds.

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Glutamate-Containing Natural Products: L-glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system. We are interested in understanding the process of glutamate excitotoxicity, a common final pathway of such conditions as Alzheimer's disease, ALS, stroke, Huntington's disease, hypoglycemia, and multiple sclerosis. Glutamate-containing natural products have been used as tools to gain a better mechanistic understanding of excitotoxicity, which may lead to therapeutic intervention for diseases involving dysfunctional glutamate receptors.


Correolide: Current immunosuppressants can have devastating side effects such as neurotoxicity, nephrotoxicity, vasculitis and myocardial necrosis. These toxicities are of obvious concern as they impose severe limitations in the therapeutic use of these drugs. The Kv1.3 potassium channels, found in T cells, have been targeted in the development of new immunosuppressive agents that may exhibit much lower toxicities than those currently in use. Correolide is a known inhibitor of these channels, making it an attractive target in the search for new non-toxic therapies.