Vishnu Hosur
Vishnu Hosur wins the 2010 John and Evelyn Neumeyer Research Award.
Vishnu recently completed his doctoral training in pharmacology under Professor Ralph Loring. The title of his dissertation is “Genetic regulation of endoplasmic reticulum chaperones and pro-inflammatory cytokines by neuronal α4β2 nicotinic receptors”.
Smokers and animals exposed to nicotine show increased expression of nicotinic receptors in some, but not all, brain areas, and this effect is strongest for the α4β2 nicotinic receptor subtype. Nicotine-induced α4β2 receptor up-regulation has been known for almost thirty years, but how it occurs is still controversial. Further, animals without 2 subunits do not self-administer nicotine, suggesting that the α4β2 receptor is important for the addictive effects of nicotine. Vishnu led a team using microarray analysis investigating whether nicotine changes expression of chaperone molecules that could lead to greater α4β2 nicotinic expression. Not only did he find that nicotine altered gene expression for several potential chaperones that may influence α4β2 nicotinic receptor subunit folding and assembly in the endoplasmic reticulum, but unexpectedly also found that nicotine treatment suppressed gene expression for several pro-inflammatory cytokines. Nicotine is known to be anti-inflammatory and neuroprotective acting through other receptors, but this work showed that α4β2 nicotinic receptors work similarly. This part of his thesis was published in the Journal of Neurochemistry http://www3.interscience.wiley.com/journal/122582638/abstract. Follow-up work demonstrated that nicotine, acting through α4β2 nicotinic receptors, can block production of inflammatory cytokines caused by bacterial lipopolysaccharides. Nicotinic receptors are ion channels when activated, but the anti-inflammatory actions of nicotine do not occur due to calcium influx or changes in the signaling molecule cAMP. Instead, nicotine acting at α4β2 nicotinic receptors, at least partially blocks the transcription factor NF-kB which is required for inflammatory cytokine synthesis. This part of Vishnu's thesis has been submitted for publication.