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Stuart R. Maudsley, Ph.D., Investigator Head, Receptor Pharmacology Unit |
Dr. Maudsley received his Ph.D. in 1997 in Pharmacology from the Department of Pharmacology at the University of Leeds where he studied the molecular mechanisms of tachykinin receptor activation and desensitization. With a Howard Hughes Medical Institute Fellowship, he moved to Duke University to work with Professor Robert J. Lefkowitz on the connectivity of G protein-coupled receptor (GPCR) signaling to tyrosine kinase pathways. During this period Dr. Maudsley developed new theories of GPCR signaling based upon the creation of higher order superstructures. Dr. Maudsley then accepted an Investigator position at the Medical Research Council at the University of Edinburgh in the United Kingdom. There he furthered the development of his concepts of the organization of GPCRs into discrete signaling structures for specific physiological functions. This work forms the basis of his research into the alteration of the GPCR signaling structures during healthy and pathological aging. |
Research Interests: For the majority of its experimental lifetime, information flow through G protein-coupled receptors (GPCRs) has been envisioned as unidirectional, i.e., changes in receptor conformation produced by extracellular agonist binding promotes the transfer of information from outside the cell inwards. Recent experimentation however, has demonstrated that receptor conformation is also controlled by protein-protein interactions occurring inside the cell. Receptor dimerization and interactions with intracellular scaffolding and signaling proteins can modify receptor structure and ligand selectivity and predetermine, from a menu of available options, which intracellular responses will predominate. In essence, the influences on receptor conformation are bi-directional; internal factors change the conformation of the receptor to reflect the status of the intracellular milieu, while extracellular factors, i.e., agonists, convey information to the cell about the external environment. This concept has critical implications for receptor theory and the design of therapeutics. Thus in complex physiological processes, e.g., aging or neurodegenerative disease, in which multiple proteins expression patterns are changed it is more likely than previously thought that GPCR signal conditioning could be affected. Therefore if indeed there is an alteration of GPCR pharmacology in these states then perhaps drug design should be targeted toward this new pharmacology rather than the standard models previously used. |
Contact Information:
Laboratory of Neurosciences Biomedical Research Center, 05C228 251 Bayview Boulevard, Suite 100 Baltimore, MD 21224-6825 Phone 410-558-8472 Fax 410-558-8323 E mail maudsleyst@grc.nia.nih.gov For more information about the Laboratory: http://www.grc.nia.nih.gov/branches/lns/index.html |
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