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John Gerdes
Associate Professor
Phone: (406) 243-4084
Email: john.gerdes@umontana.edu
After completing a B.S. in Chemistry at Colorado State University (1978), John Gerdes received a Ph.D. in Chemistry from the University of California at Riverside in 1982. Following a postdoctoral position at U. C. Berkeley, he joined Lawrence Berkeley National Laboratory (LBNL) as a staff scientist during 1986. In 1991 he began his industrial experience, working for Zeneca, Ltd., which was followed by a faculty post within the Department of Chemistry at Central Washington University (1995) where he was promoted to full professor in 2001. Subsequently, he joined the CFSN and the Department of Chemistry at the University of Montana (2001). He serves as the Director of the CSFN Molecular Computational Core Facility (2001-present). During 2006 he became a tenured faculty member within the Department of Biomedical and Pharmaceutical Sciences.
Our research encompasses a full spectrum of medicinal chemistry studies of central nervous system (CNS) pre-synaptic transporter proteins, including the serotonin transporter (SERT), norepinephrine transporter (NET) and select excitatory amino acid transporters (EAATs). A portion of our studies focuses upon computational modeling, involving superposition-consensus pharmacophore model generation, formation of comparative molecular field analysis (CoMFA) models, and protein homology models. Together, the various models serve as key criteria for the designs of new ligands and drugs for the transporter target proteins.
Model designed ligand libraries are routinely synthesized in our lab and then pharmacologically evaluated for target protein binding potency. By doing so, be are able to evaluate the predictive qualities of the models, and enhance the ligand pharmacological activities through iterative design. The small molecule agents novel therapeutic drugs, diagnostic probes and biochemical reagents.
Many of the new agents are assessed in vivo carried out with collaborators. For example, select candidate drugs are fashioned as dynamic brain imaging tracers for positron emission tomography (PET). Cerebral PET imaging provides the opportunity to utilize the radiolabeled forms of our ligands (tracers) to gain estimates of the density of the target CNS transporter proteins in living brain. Primate CNS PET measures afford deeper insights into aspects of tracer neuropharmacological kinetics and dynamics, modes of actions of CNS therapeutic interventions and biological psychiatry circuitry associated with various neurological and mental health disorders.
- Gerdes J.M., DeFina S.C., Wilson P.A., Taylor S.E.. Serotonin Transporter Inhibitors: Syntheses And Binding Potency of (rac)-2'- and (rac)-3'-Methyl-6-nitroquipazine. Bioorg Med Chem Lett 10:2643-46, 2000.
- O'Neil J.P., VanBrocklin H.F., Bolstad D.B., Gerdes J.M., Kusche B.R. Serotonin Transporter Ligands: Synthesis of (±)-[11C]2'-Methoxymethyl-6-nitroquipazine. J. Labelled Compds Radiopharm, 46:S171, 2003.
- Gerdes J.M., O'Neil J.P., Bolstad D.B., Kusche B.R., Taylor S.E., Weller M., VanBrocklin H.F. New Serotonin Transporter Radioligands: (±)-[18F]2'-Methoxy-6-nitroquipazine. NeuroImage, 22 Suppl2:T147, 2004.
- Poss M., Holley D.C., Biek R., Cox H., Gerdes J. Development of a Homology Model for Clade A Human Immunodeficiency virus type 1 gp120 to Localize Temporal Substitutions Arising in Recently Infected Women. J. Gen Virology, 85:1479, 2004.
- Thompson C.M., Davis E., Carrigan C.N., Cox H.D., Bridges R., Gerdes J.M. Inhibitors of the Glutamate Vesicular Transporter (VGLUT). Current Medicinal Chemistry 12:2041-2056, 2005.
- Gerdes J., O'Neil J., Taylor S., Eberling J., Bolstad D., Kusche B., VanBrocklin H. Design of High Affinity Tracers With Enhanced Signal-to-Noise Profiles: Novel Serotonin Transporter PET Radioligands. Molecular Imaging, 4: 220-221, 2005.
- Esslinger C.S., Agarwal S., Gerdes J., Wilson P.A., Davis E.S., Awes A.N., O'Brien E., Mavencamp T., Koch H.P., Poulsen D.J., Rhoderick J.F., Chamberlin A.R., Kavanaugh M.P., Bridges R. The Substituted Aspartate Analogue L-b-threo-Benzyl-aspartate Preferentially Inhibits the Neuronal Excitatory Amino Acid Transporter EAAT3. Neuropharmacology 49:850-861, 2005.
- Hassani M., Cai W., Holley D.C., Lineswala J.P., Maharjan B.R., Ebrahimian G.R., Seradj H., Stockdale M.G., Mohammadi F., Marivin C.C., Gerdes J.M., Beall H.D., Behforouz M. Novel Lavendaycin Analogues as Antitumor Agents: Synthesis, in vitro Cytotoxicity, Structure-Metabolism and Computational Molecular Modeling Studies with NAD(P)H:Quinone Oxidoreductase 1 (NQO1). Journal of Medicinal Chemistry, 48:7733-7749, 2005.