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Gregory Sawyer

Gregory Sawyer
Gregory Sawyer, PhD

Associate Professor of Pharmaceutical Sciences

Contact

Texas A&M Irma Lerma Rangel College of Pharmacy
1010 W. Ave. B
Kingsville, TX 78363
Phone: 361.221.0641
Fax: 361.221.0793

Biography

Ever since I first learned about G protein-coupled receptors, I have been fascinated by them. Consequently, my research and teaching interests both focus on G protein-coupled receptors. Specifically their structure, function, cloning, expression, characterization, regulation, and anterograde trafficking.    

My primary research interests focused on muscarinic acetylcholine receptors. Muscarinic receptors are G protein-coupled receptors that elicit responses to the neurotransmitter acetylcholine and they mediate a wide range of responses in the brain and periphery. Drugs that bind muscarinic receptors can be used to treat sea sickness, overactive bladder, extrapyramidal symptoms of antipsychotic drugs, Sjögren’s syndrome, COPD, and asthma. The roles of muscarinic receptors in schizophrenia and depression are currently being investigated as are drugs that bind muscarinic receptors that improve cognitive deficits associated with Alzheimer’s disease.   

Using a variety of molecular, pharmacological and biochemical techniques we characterized the agonist-dependent regulation and anterograde trafficking of muscarinic receptors. Most studies were conducted in cell lines (CHO, HEK293 and mouse embryonic fibroblast) expressing wild-type or mutant receptors. Mutant receptors were created using a PCR-based method to change the nucleotide sequence of the cDNA encoding the receptor at specific positions (i.e., site-directed mutagenesis). The pharmacology (i.e., radioligand binding and second messenger signaling) and agonist-depending trafficking (i.e., the kinetics of internalization, downregulation, and recycling) of the mutant receptor was extensively characterized and compared to that of the wild type. Using this approach, we identified domains of muscarinic M1 receptors necessary for agonist-dependent internalization and downregulation, as well as a domain necessary for the receptor to exit the endoplasmic reticulum. 

We also expressed GFP-tagged muscarinic receptors in primary neocortical neurons using recombinant lentivirus. The cell surface expression of tagged receptor was assessed using radioligand binding and the cellular localization of the receptor was determined using confocal microscopy. The goal of this study was to learn more about the domains of muscarinic receptors that regulate sorting in polar cells like neurons.

Since arriving at the Texas A&M Irma Lerma Rangel College of Pharmacy, I joined the Office of Student Affairs. In my new role, I look forward to helping professional student pharmacists accomplish their personal, academic, and career goals. I also look forward to collaborating with the Offices of the Dean, Academic Affairs, and Finance and Administration to provide a welcoming, engaging, and student-centered learning environment.

Education and Training

  • School of Medicine, University of California, Los Angeles , Department of Molecular and Medical Pharmacology, Post-doctoral Research, 1999-2001
  • College of Medicine, University of California, Irvine, PhD, Pharmacology and Toxicology, 1995-1999
  • California State University, Fresno, Molecular Biology, 1993-1995
  • Florida Institute of Technology, Melbourne, Florida, Bachelor of Science in Biological Sciences, Minor Marine Biology, 1991

Teaching Interests

  • Medical Biochemistry
  • Molecular and Cellular Biology
  • Receptors I & II
  • Principles of Drug Action
  • Molecular Techniques

Awards, Recognition and Service

  • 1999 Henry Wood Elliot Award
  • 2007 INRC Young Investigator Travel Award
  • 2009 3rd Annual Julius Axelrod Early Career Poster Session Travel Award
  • 2010 Regent’s Distinguished Teaching Award, Oklahoma State University, Center for Health Sciences
  • 2010 Regent’s Distinguished Research Award, Oklahoma State University, Center for Health Sciences
  • 2008-2011 Effects of a Small Muscarinic M1 Receptor Domain on Internalization, AREA grant, NINDS (1R15NS057742)
  • 2010 Making a M1 receptor Knock-in Mouse, Oklahoma State University, Center for Health Sciences Intramural Grant
  • 2008 Dimerization of Muscarinic M1 Receptors. Oklahoma State University, Center for Health Sciences Intramural Grant
  • 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

Representative Publications

Book chapters

  • Sawyer, G.W. and Ehlert, F.J. Using In Vitro Mutagenesis to Characterize Structure-Function Relationships in G Protein-Coupled Receptors. In: Stevens, Craig W. (Ed.) “Methods for Characterizing G Protein-Coupled Receptors” Springer-Verlag, New York, NY (In press).
  • Sawyer, G. W.,  A novel method for determining the kinetics of G protein-coupled receptor plasma membrane expression. In: Stevens, Craig W. (Ed.) “Methods for the Discovery and Characterization of G Protein-Coupled Receptors”, Springer-Verlag, New York, NY (2011).
  • Olsen, R.W. and Sawyer, G.W. GABAA receptor proteins.  Encyclopedia of Biological Chemistry.  Eds. W.J. Lennarz and M.D. Lane.  Elsevier, San Diego (2004).

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.