The altered function of any epigenetic modification also causally affects the physiological homeostasis in different pathophysiological conditions such as cancer,neurodegenerative disorders,diabetes,asthma,COPD etc.Am...The altered function of any epigenetic modification also causally affects the physiological homeostasis in different pathophysiological conditions such as cancer,neurodegenerative disorders,diabetes,asthma,COPD etc.Among the different epigenetic enzymes we focus on three important classes:lysine acetyltransferases,arginine methyltransferases and aurora kinases in the context of cancer and neurodegenerative diseases.Our laboratory has discovered several small molecule modulators of these enzymes,which may serve as lead scaffolds to design new generation therapeutics.We have shown that specific as well as broad spectrum inhibitors of lysine acetyltransferases repress the oral,liver as well as prostate cancer progression in the xenografted animal model system.Furthermore,we have shown that one of the p300 specific inhibitors discovered in our laboratory potently inhibit the multiplication of HIV in a cellular system.By using a novel histone acetyltransferase activator molecule,we find that p300/CBP mediated acetylation of histones is an important inducing factor for robust neurogenesis;which presumably contributes to long-term spatial memory.Remarkably,the p300/CBP activator treatment efficiently enhances the memory of Tau mice almost to the normal level.The molecular basis of this phenomenon is being understood.展开更多
文摘The altered function of any epigenetic modification also causally affects the physiological homeostasis in different pathophysiological conditions such as cancer,neurodegenerative disorders,diabetes,asthma,COPD etc.Among the different epigenetic enzymes we focus on three important classes:lysine acetyltransferases,arginine methyltransferases and aurora kinases in the context of cancer and neurodegenerative diseases.Our laboratory has discovered several small molecule modulators of these enzymes,which may serve as lead scaffolds to design new generation therapeutics.We have shown that specific as well as broad spectrum inhibitors of lysine acetyltransferases repress the oral,liver as well as prostate cancer progression in the xenografted animal model system.Furthermore,we have shown that one of the p300 specific inhibitors discovered in our laboratory potently inhibit the multiplication of HIV in a cellular system.By using a novel histone acetyltransferase activator molecule,we find that p300/CBP mediated acetylation of histones is an important inducing factor for robust neurogenesis;which presumably contributes to long-term spatial memory.Remarkably,the p300/CBP activator treatment efficiently enhances the memory of Tau mice almost to the normal level.The molecular basis of this phenomenon is being understood.
