Administration & Faculty
John Harrelson, Ph.D.
Assistant Professor
Pharmaceutical Science
Teaching
I introduce the concepts of drug action and drug metabolism in block 502, which includes a review of pertinent organic chemistry. I also teach the medicinal chemistry component of the integrated, team-taught Medicinal Chemistry & Pharmacology blocks (505, 507-510). I am also involved in the toxicology block (511) during the P1 year. One of my goals for P1 students is that they continue to develop problem solving and critical thinking skills, as well as the ability to seek and integrate multiple information sources.
Research Interests
I study drug metabolizing enzymes that are a part of the cytochrome P450 (CYP) superfamily of enzymes. These enzymes are important in clearing drugs from organisms but are also involved in toxic processes (drug-induced liver toxicity, drug-drug interactions, carcinogenesis, and drug sensitivities) due to the generation of reactive metabolites. I am interested in understanding the mechanisms involved in substrate binding to CYP enzymes and how the presence of allosteric effectors (i.e., a second substrate or other effector) impacts substrate dynamics. An understanding of such mechanisms should contribute to the generation of more accurate kinetic models. These studies involve kinetic isotope effect experiments to generate information about substrate dynamics. I am also interested in the utilization of mechanism-based inactivators to probe P450 structure-function relationships. Students working in this lab have the opportunity to gain experience with a variety of techniques including: GC-MS, HPLC, enzyme kinetics, kinetic isotope effects, metabolite extraction, identification, and quantification, as well as organic synthesis and purification using established protocols.
Education and Relevant Experience
Ph.D., Medicinal Chemistry, 2005, University of Washington
B.S., Chemistry, 1994, Gonzaga University
Assistant Professor of Pharmaceutical Sciences, Pacific University (2006-Present)
Assistant Professor of Chemistry, Gonzaga University (2005-2006)
NIH Pharmacological Sciences Trainee (1999-2001; 2003-2004)
Executive Officer, Newport Chemical Depot, Newport, IN (2002-2003)
Production Chemist, Molecular Probes, Eugene, OR (1997-1998)
Chemical Officer, 1st Cavalry Division, Ft. Hood, TX (1994-1997)
Publications and Presentations
Harrelson JP, Nelson SD. Surveying The CYP2E1 and CYP2A6 Active Sites Using Intramolecular Kinetic Isotope Effects, 36 Drug Metabolism Reviews (2004) Abstract 145.
Harrelson JP, Henne KR, Alonso DO, Atkins WM, Nelson SD. Substrate Dynamics and Multiple-Ligand Binding in CYP2A6: Investigating Mechanisms of P450 Allosterism Using Deuterium Isotope Effects (poster), Gordon Research Conference on Drug Metabolism, Plymouth, NH (2006)
Harrelson JP, Henne KR, Alonso DO, Nelson SD. A comparison of substrate dynamics in human CYP2E1 and CYP2A6, Biochemical and Biophysical Research Communications 352 (2007) 843-849.
Harrelson JP, Atkins WM, Nelson SD. CYP2A6, The Major Nicotine Metabolizing Enzyme, Simultaneously Binds Multiple Xylene Ligands and Exhibits Allosteric Kinetics. Manuscript in preparation (2007).