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Dr. Palmer Taylor
Molecular Recognition in the Cholinergic Nervous System
Palmer Taylor, Ph.D.
Sandra and Monroe Trout Professor of Pharmacology
Founding and Emeritus Dean
Skaggs School of Pharmacy & Pharmaceutical Sciences
Research Summary: Neuropharmacology Synapses and Receptor Mechanisms
Dr. Taylor’s studies have employed spectroscopic physical methods, X ray crystallography, sequence and three dimensional structural determinations to investigate the principles of molecular recognition. He has worked with nicotinic acetylcholine receptors and acetylcholinesterase since the mid-1970’s with current interests directed to structure and dynamics as they relate to ligand design. For acetylcholinesterase (AChE), reactivating antidotes to organophosphate nerve agent and insecticide exposure are designed to confer oral bioavailability and CNS reactivation capabilities. These studies evolved from collaboration with Barry Sharpless of TSRI using AChE as the first target template for freeze-frame, click chemistry to synthesize in situ selective cholinesterase inhibitors and reactivator antidotes. Collaborative studies with nicotinic receptors also employ click-chemistry in structure- guided drug design. In this case, a soluble surrogate for the extracellular domain of the nicotinic receptor is used as the template for the in situ synthesis of novel nicotinic receptor ligands directed to the α7 subtype. More recently, Taylor has conducted studies into the structure and function of a post-synaptic adhesion protein homologous to AChE, neuroligin, and its pre- synaptic partner, neurexin. Studies employ both crystallographic and solution-based techniques and are directed to macromolecular recognition of ectodomain adhesion molecules.
B.S and Ph.D. in Physical Pharmacy University of Wisconsin; Post-doctoral fellowships NIH and Cambridge University, United Kingdom.
Highlighted Honors and Awards:
1981-82 Fogarty Fellow, Darwin College, Cambridge University; 1988 – Elected, President, American Society for Pharmacology & Experimental Therapeutics; 1995 – Elected to Honorary Membership, American Society for Clinical Investigation; 1998 – Elected to the National Academy of Sciences; 1999-2009 – NIGMS Merit Award; 2003 – Torald Sollmann Award in Pharmacology; 2007 – Elected Fellow, AAAS; Univ. of Bologna, Alma Mater Studiorum; 2009 – Julius Axelrod Award in Research, American Society for Pharmacology in Experimental Therapeutics; 2011 – Inaugural Andrej Zupancic SINAPSA Lecture (FENS); 2012 – Scholar Endowed Lectures in Psychopharmacology, Baylor Univ.; 2012 – Univ. of Wisconsin Citation in Pharmacy Education; Theodore Brody Award, Michigan State University; 2013 – Chevalier dans l’Ordre de la Legion d'Honneur, France; 2014 Asian Heritage Award in Medicine; 2015 International Associated Laboratory (LIA) CNRS France; 2016 – Revelle Award, University of California San Diego.
Founding Chair, Dept. of Pharmacology UCSD (1987-2003); Founding Dean, Skaggs School of Pharmacy & Pharm. Sci. (2002-14); President, Amer. Soc. For Pharmacology & Exp. Therapeutics (1995); NIH National Advisory Councils NIGMS (1988-92), NIEHS (2009-13).
- Lectures and course directorships in pharmacology and toxicology to medical, pharmacy and Ph.D. students.
- Co-editor and co-author: Goodman & Gilman’s, Pharmacological Basis of Therapeutics, Pratt and Taylor Principles of Drug Action.
Selected Recent Publications (from >400 peer-reviewed articles, reviews and chapters)
- Miller, M.T., et al (2011). The crystal structure of the α-neurexin-1 extracellular region reveals a hinge point for mediating synaptic adhesion and function. Structure, 19, 767-778 Cover Article
- Grimster, N.P., et al (2012). Generation of candidate ligands for nicotinic acetylcholine receptors via in situ click chemistry with a soluble acetylcholine binding protein template. J Amer. Chem. Soc., 134:6732- 6740.
- Radic, Z., et al (2012). Refinement of structural leads for centrally acting oxime reactivators of phosphylated cholinesterases. J. Biol. Chem. 287: 11798-11809
- Kaczanowska, K., et al (2014). Structural basis for cooperative interactions of substituted 2- aminopyrimidines with the acetylcholine binding protein. Proc. Natl. Acad. Sci. 111:10749-54
- Sit, R.K., et al (2014). Imidazole aldoximes effective in assisting butyrylcholinesterase catalysis of organophosphate detoxification. J. Med. Chem 57:1378-89