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 Tae H. JiProfessor of Chemistry
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Research interestsAlzheimer’s Disease (AD): Kalirin-7 is a protein of 1,663 amino acids, which is predominantly expressed in the adult brain and plays crucial roles in growth and maintenance of neurons. Our group has discovered that Kalirin-7 mRNA and protein are under-expressed in the hippocampus specimens from 19 AD (Alzheimer’s disease) patients compared to the specimens from 15 controls. In addition, we have found that Kalirin-7 associates with iNOS in the hippocampus, and therefore, Kalirin-7 is complexed with iNOS less in AD hippocampus than in control hippocampus. In cultured cells, Kalirin-7 associates with iNOS and down-regulates the enzyme activity. Remarkably, the iNOS (inducible NO synthase) activity is considerably higher in the hippocampus specimens from AD patients than the specimens from controls. Our study suggests that the under-expression of Kalirin in AD hippocampus contributes to the increased production of deleterious NO in AD brain, further damaging the AD brain. In addition, we demonstrate that the highly conserved 33 amino acid sequence, K617-H649, of the >1,660 amino acid Kalirin is responsible for the iNOS suppression and that the short peptide mimic corresponding to the K617-H649 sequence down-regulates the iNOS activity in cultured cells. Our results may provide a novel approach to the AD therapeutics. Signal Generation by Receptors: It is generally thought that, to activate a receptor molecule, it has to bind hormone and the hormone-bound receptor or receptor complex activates itself (cis-activation). In contrast to this cis-activation, there is the emerging evidence that a free (nonliganded) receptor molecule can be activated by another receptor molecule that is complexed with hormone (trans-activation). Trans-activation is difficult to test, because it has to be differentiated from cis-activation and signal generation needs to be distinguished from hormone binding. We have established a large library of two groups of mutant receptors (>1,000), one deficient in hormone binding and the other deficient in signal generation. Co-expression of a binding-deficient mutant and a signal-deficient mutant in a cell rescues signal generation, which has established trans-activation. What was surprising was that trans-activation and cis-activation generate different hormone signals. Our studies provide a novel approach to inducing a specific hormone signal without invoking other signals associated with the hormone.
PublicationsMore Information on our Research GroupPostdoctoral Positions |
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