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.
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.
