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Greg W. Sawyer, Ph.D.Gregory W. Sawyer, Ph.D.
Associate Professor of Biochemistry

gregory.sawyer@okstate.edu
Office 918.561.1221 Room E-421
Lab 918.561.8441, Room E-465

Education | Professional Experience | Professional Societies | Honors and Awards | Instructional Activity at OSU-CHS | Representative Publications and Presentations | Major Research Interests

Education

1999-2001
Postdoctoral, University of California, Los Angeles, Los Angeles, CA

1999
Ph.D. (Pharmacology and Toxicology), University of California, Irvine, Irvine, CA

1993-1995
Molecular Biology, California State University, Fresno, Fresno, CA

1991
B.S. (Biological Sciences, Minor Marine Biology), Florida Institute of Technology, Melbourne, FL

Professional Experience

2007-Present
Associate Professor, Department of Biochemistry and Microbiology, Oklahoma State University, Center for Health Sciences, Tulsa, OK

2004-2007
Assistant Professor, Department of Biochemistry and Microbiology, Oklahoma State University, Center for Health Sciences, Tulsa, OK

2001-2004
Assistant Professor, Department of Pharmacology and Physiology, Oklahoma State University, Center for Health Sciences, Tulsa, OK

1999-2001
Postdoctoral Fellow, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, School of Medicine, Los Angeles, CA

1994-1995
Laboratory Technician, Department of Virology, California Veterinary Diagnostic Laboratory System, Fresno Branch, Fresno, CA

1993-1995
Teaching Assistant, Department of Biology, California State University, Fresno, Fresno, CA

Professional Societies

Society for Neuroscience
American Society for Pharmacology and Experimental Therapeutics (ASPET)

Honors and Awards

1999    Henry Wood Elliot Award
2007    INRC Young Investigator Travel Award
2009    3rd Annual Julius Axelrod Early Career Poster Session Travel Award

Grant Awards
2008-2011
Effects of a Small Muscarinic M1 Receptor Domain on Internalization, AREA grant, NINDS (1R15NS057742)

2008
Dimerization of Muscarinic M1 Receptors.  Oklahoma State University, Center for Health Sciences Intramural Grant (CHS-0803)

2007
Internalization of Muscarinic M1 Receptors.  Oklahoma State University, Center for Health Sciences Intramural Grant  

2003-2006
Trafficking and Signaling of Muscarinic Receptors.  Oklahoma Center for the Advancement of Science and Technology Health Research Grant (HR03-107S)

2000-2001
Labeling the Neuroactive Steroid Site of GABA Receptors.  NIH-NRSA Postdoctoral Fellowship (1F32NS11015-01)

1999
Regent’s Dissertation Fellowship

Instructional Activity at OSU-CHS

  • Medical Biochemistry – team taught MS I course
  • Molecular and Cellular Biology – team taught graduate course
  • Receptors I & II – team taught graduate courses

Representative Publications and Presentations

Peer-reviewed articles

Thangaraju, A. and Sawyer, G.W. Comparison of the kinetics and extent of muscarinic M1–M5 receptor internalization, recycling and downregulation in Chinese hamster ovary cells.  European Journal of Pharmacology.  650, 534-543, 2011.

Sawyer, G.W., Ehlert, F.J., and Shults, C.A.  A Conserved Motif in the Membrane Proximal C-Terminal Tail of Human Muscarinic M1 Acetylcholine Receptors Affects Plasma Membrane Expression.  Journal of Pharmacology and Experimental Therapeutics.  332(1)76-86, 2010.

Brasel, C.M., Sawyer, G.W., and Stevens, C.W.  A pharmacological comparison of the cloned frog and human mu opioid receptors reveals differences in opioid affinity and function.  European Journal of Pharmacology 599: 36-43, 2008.

Sawyer, G.W., Ehlert, F.J., and Shults, C.A.  Cysteine Pairs in the Third Intracellular Loop of the Muscarinic M1 Acetylcholine Receptor Play a Role in Agonist-Induced Internalization.  Journal of Pharmacology and Experimental Therapeutics. 324:196-205, 2008.

Li, G.D., Chiara, D.C., Sawyer, G.W., Husain, S.S., Olsen, R.W., and Cohen, J.B. Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog. Journal of Neuroscience. 26(45):11599-605, 2006.

Sawyer, G.W., Ehlert, F.J., and Hart, J.P. Determination of the Rate of Muscarinic M1 Receptor Plasma MembraneDelivery Using A Regulated Secretion/Aggregation System.  Journal of Pharmacological and Toxicological Methods. 53(3):219-33, 2006.
 
Sawyer, G.W. Chiara, D.C. Olsen, R.W. and Cohen, J.B. Identification of the bovine gamma-aminobutyric acid type A receptor alpha subunit residues photolabeled by the imidazobenzodiazepine [3H]Ro15-4513. Journal of Biological Chemistry. 277(51):50036-45, 2002.

Nymann-Andersen J., Sawyer G.W., and Olsen R.W. Interaction between GABAA receptor subunit intracellular loops: implications for higher order complex formation. Journal of Neurochemistry. 83(5):1164-71, 2002.

Ehlert, F.J., Ansari, K.Z., Shehnaz, D., Sawyer, G.W., and Griffin, M.T. Acetylcholine-induced desensitization of the muscarinic contractile response in guinea pig ileum is inhibited by pertussis toxin-treatment.  J. Pharmacol. Ex. Ther., 299: 1126-1132, 2001.

Sawyer, G.W., Lambrecht G., and Ehlert, F.J.  Functional role of muscarinic M2 receptors in a a,b-methylene ATP-induced, neurogenic contractions in guinea pig ileum.  Br. J. Pharmacol., 129:1458-1464, 2000.

Sawyer, G.W. and Ehlert, F.J.  M3 receptor inactivation reveals a pertussis toxin-sensitive contractile response in the guinea pig colon: evidence for M2/M3 receptor interactions. J. Pharmacol. Ex. Ther. 289:464-476, 1999.

Ehlert, F.J., Griffin, M.T., and Sawyer, G.W., and Bailon, R.  A simple method for estimations of agonist activity at receptor subtypes: comparison of native and cloned M3 muscarinic receptors in guinea pig ileum and transfected cells. J. Pharmacol. Ex. Ther. 289:981-992, 1999.

Ehlert, F.J., Sawyer, G.W., and Esqueda, E.E.  Contractile role of M2 and M3 muscarinic receptors in gastrointestinal smooth muscle.  Life Sci. 64:387-394, 1999.

Sawyer, G.W. and Ehlert, F.J.  Pertussis toxin increases isoproterenol-induced relaxation in field-stimulated ileum.  European J. Pharmacol. 367:81.84, 1999.

Sawyer, G.W. and Ehlert, F.J.  Contractile roles of the M2 and M3 muscarinic receptors in the guinea pig colon. J. Pharmacol. Ex. Ther. 284:269-277, 1998.

Ehlert, F.J., Ostrom, R.S., and Sawyer, G.W.  Subtypes of the muscarinic receptor in smooth muscle.  Life Sci. 61:1729-1740, 1997.

Selected Meeting Abstracts

Sawyer, G.W. and Shults, C.A., Mutation of amino acid residues in the C-terminal tail and near the base of transmembrane spanning domain 1 affect M1 receptor plasma membrane expression. Annual Society for Neuroscience Meeting, Chicago, Il., October 17-21, 2009.

Thangaraju, A. and Sawyer, G.W., Receptor domains involved in agonist-dependent muscarinic M1 receptor recycling. Annual Society for Neuroscience Meeting, Chicago, Il., October 17-21, 2009.

Sawyer, G.W.  Use of a regulated secretion/aggregation system to determine the rate of muscarinic M1 and M2 receptor plasma membrane insertion.  3rd Annual Julius Axelrod Poster Session, Annual Society for Neuroscience Meeting, Chicago, Il., October 18, 2009.  

Brasel, C.M., Sawyer, G.W. and Stevens, C.W. A comparison of agonist-dependent activity in the cloned frog and human mu opioid receptors. International Narcotics Research Conference (INRC) Annual Meeting, Portland, Oregon, USA. July 12-17, 2009. 

Sawyer, G.W. and Shults, C.A., Amino acid residues in transmembrane domain 1 and in the membrane proximal C-tail of muscarinic M1 receptors are necessary for transport-competent folding.  Experimental Biology (ASPET) Meeting, New Orleans, LA, U.S.A., April 18-22, 2009. 

Thangaraju, A. and Sawyer, G.W. Comparison of agonist-dependent internalization, downregulation and recycling of M1-M5 receptors in CHO cells.  Experimental Biology (ASPET) Meeting, New Orleans, LA, U.S.A., April 18-22, 2009.

Sawyer, G.W. Cysteine Residues in the Third Intracellular Loop of Muscarinic M1 Receptors Play a Role in Internalization.  Recent Advances in Muscarinic Receptor Pharmacology & Therapeutics, San Diego, CA, U.S.A., April 4-5th, 2008.

Stevens, C.W., Brasel, C.M., and Sawyer, G.W., Characterization of receptor internalization and inhibition of cAMP in cell lines expressing amphibian or human mu opioid receptors. Experimental Biology (ASPET) Meeting, San Diego, CA, U.S.A., April 5-9, 2008.

Brasel, C.M., Sawyer, G.W., and Stevens, C.W.  Comparison of agonist-induced internalization profiles in the amphibian and human mu opioid receptors.  Annual Society for Neuroscience Meeting, 2007.

Sawyer, G.W.  A small domain in the C-terminal tail of muscarinic M1 and M4 receptors is necessary for expression on the plasma membrane. Annual Society for Neuroscience Meeting, 2007.

 Sawyer, G.W., C.W. Stevens, and Brasel, C.M, Pharmacological comparison of human and frog MOR. International Narcotics Research Conference (INRC) Annual Meeting, Berlin, Germany, July 8-13, 2007.

C.W. Stevens, Sawyer, G.W., and Brasel, C.M, Pharmacological comparison of human and frog mu opioid receptors. Committee on Problems of Drug Dependence (CPDD) Annual Meeting, Quebec City, Canada, June 16-21, 2007.

Major Research Interests

Our laboratory is interested in learning more about the agonist-dependent regulation and trafficking of muscarinic receptors.  Muscarinic receptors elicit responses to the endogenous neurotransmitter acetylcholine and mediate a wide range of responses in the central nervous system and periphery.  Muscarinic receptors are targets for sea sickness, overactive bladder, and asthma medications.    

We use a variety of molecular, pharmacological and biochemical techniques to study the agonist-dependent regulation and trafficking of muscarinic receptors.  Most studies are conducted in cell lines (CHO, HEK293 and mouse embryonic fibroblast) expressing wild-type or mutant receptors.  Mutations are introduced into muscarinic receptor sequences using PCR and mutant receptors are expressed in cell lines using a lipid reagent.  We also express muscarinic receptors in primary neocortical neurons using a recombinant lentivirus.  The cell surface expression of muscarinic receptor is accessed using radioligand binding assays and the cellular localization of recombinant GFP-tagged receptor is determined using epi-fluorescence microscopy.  The functional responses of muscarinic receptors expressed in cell lines or tissue is characterized using either phosphoinositide hydrolysis or adenylyl cyclase assays and agonists like carbachol or oxotremorine-M.

Our current research focuses on identifying and characterizing mutations that affect the agonist-dependent regulation (i.e., internalization, desensitization, and downregulation) of muscarinic M1 receptors and the kinetics of muscarinic M1 and M2 receptor plasma membrane insertion.