Dr. Wecker's general interests are to understand how brain chemistry affects or determines behaviors with an emphasis on the etiology and treatment of neuropsychiatric and neuromotor disorders. Multidisciplinary approaches are used to elucidate how age, drugs of abuse, and environmental and genetic factors affect both brain chemistry and behavior. A major emphasis has focused on cholinergic mechanisms in the brain, particularly on the role and regulation of nicotinic receptors. Early studies demonstrated that sustained supplementation of rats with choline supports the synthesis of acetylcholine during conditions of increased neuronal demand and increases the density of neuronal nicotinic receptors in the brain. Since that time studies have focused on characterizing the regulation of alpha4beta2 nicotinic receptors and have demonstrated that these receptors are regulated by phosphorylation/dephosphorylation mechanisms that alter receptor formation, maturation and expression, and that sustained nicotinic receptor activation modifies these events.
Current studies are investigating the role of neuronal nicotinic receptors in ataxia, and mechanisms mediating the neurotrophic actions of nicotinic agonists. Concurrent investigations are elucidating the role of these receptors in mediating both nicotine and alcohol addiction, and how perturbations in receptor expression during adolescence can predispose the adult brain to drug-seeking behavior. Results from these studies will further our understanding of the role and regulation of these receptors in neuropsychiatric and neuromotor disorders, and may lead to new strategies for the treatment of these disorders.
Awards/Honors
State University of New York College at Cortland Distinguished Alumni Award (State University of New York - 2016)
Outstanding Faculty Award (USF - 2013)
Fifth Annual Theodore M. Brody Distinguished Lecturer (Michigan State University - 2012)
Elected Fellow (American Association for the Advancement of Science - 2012)
Interprofessionalism Award (USF Health School of Physical Therapy & Rehabilitation Sciences - 2011)
Presidential Faculty Award for Excellence (USF - 2003)
Faculty Outstanding Teacher Award (USF College of Medicine - 1999)
Professorial Excellence Program Award (USF - 1998)
Invited Member (The Dana Alliance for Brain Initiatives - 1998)
Sophomore Class Outstanding Instructor (USF College of Medicine Class of 1999 - 1998)
Most Outstanding Pre-Clinical Professor Award (USF College of Medicine Class of 1998 - 1997)
Distinguished Teaching Award (USF College of Medicine Class of 1996 - 1996)
Distinguished Research Professor (University of South Florida - 1995)
Alumni Honor Roll (State University of New York - 1995)
Young Environmental Scientist Health Research Grant Award (National Institute of Environmental Health Sciences - 1979)
Outstanding Young Scientist Award (Smith Kline and French Laboratories - 1979)
Distinguished Young Alumnus Award (State University of New York College at Cortland - 1978)
Andrew W. Mellon Foundation Teacher-Scientist Award (Andrew W. Mellon Foundation - 1975)
Memberships
Chair of the Section on Pharmaceutical Sciences (American Association for the Advancement of Science, 2017 - 2018)
Treasurer (Federation of American Societies for Experimental Biology (FASEB), 2012 - 2014)
President (American Society for Pharmacology and Experimental Therapeutics (ASPET), 2011 - 2012)
Treasurer-elect (Federation of American Societies for Experimental Biology (FASEB), 2011 - 2012)
President-elect (American Society for Pharmacology and Experimental Therapeutics (ASPET), 2010 - 2011)
Secretary/Treasurer (American Society for Pharmacology and Experimental Therapeutics (ASPET), 2006 - 2007)
Program Committee Chair (American Society for Pharmacology and Experimental Therapeutics (ASPET), 1999 - 2002)
Recent Publications
Wecker L, Marrero-Rosado B, Engberg ME, Johns BE, Philpot RM. 3-Acetylpyridine neurotoxicity in mice.Neurotoxicology. 58: 143-152, 2017.
Zesiewicz TA, Stephenson JB, Kim SH, Sullivan KL, Jahan I, Huang Y, Salemi JL, Wecker L, Shaw JD, Gooch CL. Longitudinal gait and balance decline in Friedreich''s Ataxia: A pilot study.Gait & posture. 55: 25-30, 2017.
Schroeder RA, Wecker L, Philpot RM. Obstacles and Opportunities for Cholinergic Drug Development in the Treatment of Cognitive Disorders.Current Pharmaceutical Design. 22(14) : 1981-5, 2016.
Young MF, Wecker L. Regulation of Gait and Balance: The Underappreciated Role of Neuronal Nicotinic Receptor Agonists.Current Pharmaceutical Design. 22(14) : 1998-2003, 2016.
Philpot RM, Ficken M, Wecker L. Doxorubicin and cyclophosphamide lead to long-lasting impairment of spatial memory in female, but not male mice.Behavioural Brain Research. 307: 165-75, 2016.
Wecker L. Where are the women?Academic medicine : journal of the Association of American Medical Colleges. 90(8) : 1003, 2015.
Stephenson J, Zesiewicz T, Gooch C, Wecker L, Sullivan K, Jahan I, Kim SH. Gait and balance in adults with Friedreich''s ataxia.Gait and Posture. 41(2) : 603-7, 2015.
Lambert CS, Philpot RM, Engberg ME, Johns BE, Wecker L. Analysis of gait in rats with olivocerebellar lesions and ability of the nicotinic acetylcholine receptor agonist varenicline to attenuate impairments.Behav Brain Res. 291: 342-350, 2015.
Lambert CS, Philpot RM, Engberg ME, Johns BE, Kim SH, Wecker L. Gait analysis and the cumulative gait index (CGI): Translational tools to assess impairments exhibited by rats with olivocerebellar ataxia.Behav Brain Res. 274: 334-43, 2014.
Philpot, R.M., Engberg, M.E. and Wecker, L. Ethanol Conditioned Place Preference and Alterations in ΔFosB Following Adolescent Nicotine Administration Differ in Rats Exhibiting High or Low Behavioral Reactivity to a Novel EnvironmentBehav Brain Res. 262: 101-8, 2014.
Fernandez JW, Grizzell JA, Philpot RM, Wecker L. Postpartum depression in rats: differences in swim test immobility, sucrose preference and nurturing behaviors.Behav Brain Res. 272: 75-82, 2014.
Fernandez, J.W., Grizzell, J.A. and Wecker, L. The role of estrogen receptor and nicotinic cholinergic receptors in postpartum depressionProg. Neuropsychopharm. Biol. Psychiat.. 40: 199-206, 2013.
Wecker L, Engberg ME, Philpot RM, Lambert CS, Kang CW, Antilla JC, Bickford PC, Hudson CE, Zesiewicz TA, Rowell PP. Neuronal nicotinic receptor agonists improve gait and balance in olivocerebellar ataxia.Neuropharmacology. 73: 75-86, 2013.
Zesiewicz TA, Greenstein PE, Sullivan KL, Wecker L, Miller A, Jahan I, Chen R, Perlman SL. A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3.Neurology. 78(8) : 545-50, 2012.
Philpot RM, Engberg ME, Wecker L. Effects of nicotine exposure on locomotor activity and pCREB levels in the ventral striatum of adolescent rats.Behavioural Brain Res. 230(1) : 62-8, 2012.
Papke RL, Wecker L, Stitzel JA. Activation and inhibition of mouse muscle and neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.The Journal of pharmacology and experimental therapeutics. 333(2) : 501-18, 2010.
Ikonomovic MD, Wecker L, Abrahamson EE, Wuu J, Counts SE, Ginsberg SD, Mufson EJ, Dekosky ST. Cortical alpha7 nicotinic acetylcholine receptor and beta-amyloid levels in early Alzheimer disease.Archives of Neurology. 66(5) : 646-51, 2009.
Philpot RM, Wecker L, Kirstein CL. Repeated ethanol exposure during adolescence alters the developmental trajectory of dopaminergic output from the nucleus accumbens septi.International Journal of Developmental Neuroscience : The official journal of the International Society for Developmental Neuroscience. 27(8) : 805-15, 2009.
Pollock VV, Pastoor T, Katnik C, Cuevas J, Wecker L. Cyclic AMP-dependent protein kinase A and protein kinase C phosphorylate alpha4beta2 nicotinic receptor subunits at distinct stages of receptor formation and maturation.Neuroscience. 158(4) : 1311-25, 2009.
Philpot RM, Wecker L. Dependence of adolescent novelty-seeking behavior on response phenotype and effects of apparatus scaling.Behavioral neuroscience. 122(4) : 861-75, 2008.
Pollock VV, Pastoor TE, Wecker L. Cyclic AMP-dependent protein kinase (PKA) phosphorylates Ser362 and 467 and protein kinase C phosphorylates Ser550 within the M3/M4 cytoplasmic domain of human nicotinic receptor alpha4 subunits.Journal of neurochemistry. 103(2) : 456-66, 2007.
Severance EG, Zhang H, Cruz Y, Pakhlevaniants S, Hadley SH, Amin J, Wecker L, Reed C, Cuevas J. The alpha7 nicotinic acetylcholine receptor subunit exists in two isoforms that contribute to functional ligand-gated ion channels.Molecular pharmacology. 66(3) : 420-9, 2004.
Pacheco MA, Pastoor TE, Wecker L. Phosphorylation of the alpha4 subunit of human alpha4beta2 nicotinic receptors: role of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC).Brain research. Molecular brain research. 114(1) : 65-72, 2003.
Guo X, Wecker L. Identification of three cAMP-dependent protein kinase (PKA) phosphorylation sites within the major intracellular domain of neuronal nicotinic receptor alpha4 subunits.Journal of neurochemistry. 82(2) : 439-47, 2002.
Wecker L, Guo X, Rycerz AM, Edwards SC. Cyclic AMP-dependent protein kinase (PKA) and protein kinase C phosphorylate sites in the amino acid sequence corresponding to the M3/M4 cytoplasmic domain of alpha4 neuronal nicotinic receptor subunits.Journal of neurochemistry. 76(3) : 711-20, 2001.
Hsu YN, Edwards SC, Wecker L. Nicotine enhances the cyclic AMP-dependent protein kinase-mediated phosphorylation of alpha4 subunits of neuronal nicotinic receptors.Journal of neurochemistry. 69(6) : 2427-31, 1997.
Clark MA, Williams JF, Gottschall PE, Wecker L. Effects of phenobarbital and interleukin-6 on cytochrome P4502B1 and 2B2 in cultured rat hepatocytes.Biochemical pharmacology. 51(5) : 701-6, 1996.
Hsu YN, Amin J, Weiss DS, Wecker L. Sustained nicotine exposure differentially affects alpha 3 beta 2 and alpha 4 beta 2 neuronal nicotinic receptors expressed in Xenopus oocytes.Journal of neurochemistry. 66(2) : 667-75, 1996.
Yu ZJ, Wecker L. Chronic nicotine administration differentially affects neurotransmitter release from rat striatal slices.Journal of neurochemistry. 63(1) : 186-94, 1994.
Anandatheerthavarada HK, Williams JF, Wecker L. Differential effect of chronic nicotine administration on brain cytochrome P4501A1/2 and P4502E1.Biochemical and biophysical research communications. 194(1) : 312-8, 1993.
Anandatheerthavarada HK, Williams JF, Wecker L. The chronic administration of nicotine induces cytochrome P450 in rat brain.Journal of neurochemistry. 60(5) : 1941-4, 1993.
Zawia N, Arendash GW, Wecker L. Basal forebrain cholinergic neurons in aged rat brain are more susceptible to ibotenate-induced degeneration than neurons in young adult brain.Brain research. 589(2) : 333-7, 1992.
Coutcher JB, Cawley G, Wecker L. Dietary choline supplementation increases the density of nicotine binding sites in rat brain.The Journal of pharmacology and experimental therapeutics. 262(3) : 1128-32, 1992.
Dolezal V, Wecker L. Modulation of acetylcholine release from rat striatal slices: interaction between 4-aminopyridine and atropine.The Journal of pharmacology and experimental therapeutics. 258(3) : 762-6, 1991.
Wecker L. The synthesis and release of acetylcholine by depolarized hippocampal slices is increased by increased choline available in vitro prior to stimulation.Journal of neurochemistry. 57(4) : 1119-27, 1991.
Dolezal V, Wecker L. Muscarinic receptor blockade increases basal acetylcholine release from striatal slices.The Journal of pharmacology and experimental therapeutics. 252(2) : 739-43, 1990.
Wecker L, Cawley G, Rothermel S. Acute choline supplementation in vivo enhances acetylcholine synthesis in vitro when neurotransmitter release is increased by potassium.Journal of neurochemistry. 52(2) : 568-75, 1989.
Miller LG, Greenblatt DJ, Roy RB, Lopez F, Wecker L. Dietary choline intake modulates benzodiazepine receptor binding and gamma-aminobutyric acidA receptor function in mouse brain.The Journal of pharmacology and experimental therapeutics. 248(1) : 1-6, 1989.
Wecker L, Reinhardt RR. Adenosine inhibits choline kinase activity and decreases the phosphorylation of choline in striatal synaptosomes.Journal of neurochemistry. 50(6) : 1945-51, 1988.
Wecker L. Influence of dietary choline availability and neuronal demand on acetylcholine synthesis by rat brain.Journal of neurochemistry. 51(2) : 497-504, 1988.
Wecker L, Rothermel S, Cawley G. Chronic choline supplementation attenuates the behavioral effects of pentobarbital.Pharmacology, biochemistry, and behavior. 28(4) : 469-75, 1987.
Flynn CJ, Wecker L. Concomitant increases in the levels of choline and free fatty acids in rat brain: evidence supporting the seizure-induced hydrolysis of phosphatidylcholine.Journal of neurochemistry. 48(4) : 1178-84, 1987.
Flynn CJ, Wecker L. Elevated choline levels in brain. A non-cholinergic component of organophosphate toxicity.Biochemical pharmacology. 35(18) : 3115-21, 1986.
Wecker L. Neurochemical effects of choline supplementation.Canadian journal of physiology and pharmacology. 64(3) : 329-33, 1986.
Wecker L, Trommer BA. Effects of chronic (dietary) choline availability on the transport of choline across the blood-brain barrier.Journal of neurochemistry. 43(6) : 1762-5, 1984.
Reinhardt RR, Wecker L, Cook PF. Kinetic mechanism of choline kinase from rat striata.The Journal of biological chemistry. 259(12) : 7446-52, 1984.
Reinhardt RR, Wecker L. Evidence for membrane-associated choline kinase activity in rat striatum.Journal of Neurochemistry. 41(3) : 623-9, 1983.
Schmidt DE, Wecker L. CNS effects of choline administration: evidence for temporal dependence.Neuropharmacology. 20(6) : 535-9, 1981.
Wecker L, Dettbarn WD, Schmidt DE. Choline administration: modification of the central actions of atropine.Science (New York, N.Y.). 199(4324) : 86-7, 1978.
