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Tony Giordano, Ph.D. Major Research Interests: Despite advances in identifying novel disease associated genes and mechanisms, many current cancer treatments are similar to those used decades ago in that they do not specifically target cancer cells, rather they target rapidly dividing cells or normal proteins over expressed in cancer cells. The focus of my lab is to determine the molecular mechanisms by which cancer cells efficiently translate RNAs, such as Her2/neu, that are in a poor context for translation and to identify small molecules that target these mechanisms as better cancer treatments. To understand these mechanisms, we use a combination of high throughput screens to identify small molecules that effect translation and then use these small molecule inhibitors to study effects on pathways and mechanisms giving rise to the cancer specific increased translational efficiency. Alzheimer's disease is not well understood nor are there any current treatments that are effective in a large number of patients. We are focusing on the role of APP and the amyloid peptide in changes in neuronal cell signaling. A major focus of the laboratory is the cloning of the receptors to which amyloid binds and how binding impacts signal transduction. As series of molecular targets are identified in these projects, RNAi is used to validate their relevance. The laboratory
has established ongoing collaborations with medicinal chemists to analyze target specific structure activity relationship
for lead optimization with the ultimate goal of developing novel, highly specific drugs. Recent Publications: Chopra, M., Pachuck, C., Satishchandran, C., Giordano, T. (2002) Using RNA interference to modulate gene expression. Targets 1: 102-108. Zhu, X., Giordano, T., Yu, Q., Holloway, H.W., Perry, T.A., Lahiri, D.K., Brossi, A., Greig , N.H. (2003) Thiothalidomides: Novel isoteric analogues of thalidomide with enhanced TNF- inhibitory activity. J. Med. Chem. 46:5222-5229. Greig , N.H. , Giordano, T., Zhu, X., Yu, Q.-S., Perry, T.A., Holloway, H.W., Utsuki, T., Brossi, A., Rogers , J.T., Sambamurti, K., Lahiri, D.K. (2004) Thalidomide-based TNF- inhibitors for neurodegenerative diseases. Acta. Neurobiol. Exp. 64:1-9. Contact Info:
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