William P. Melega, Ph.D.

Work Address:
Los Angeles, CA 90095

Professor, Jane and Terry Semel Institute for Neuroscience and Human Behavior
Professor In-Residence, Molecular & Medical Pharmacology
Member, Brain Research Institute, Molecular Pharmacology GPB Home Area
Research Interests
This research program is focused on molecular mechanisms of basal ganglia neuroplasticity associated with neurodegenerative diseases and drug abuse. Analytical techniques include a wide range of biochemical, molecular and behavioral approaches. Specific projects include: 1- Biochemical studies on the acute and long term effects of methamphetamine. Studies are investigating mechanisms of neuronal adaptation following long term methamphetamine exposure in rodents. 2- Intervention strategies for neurodegenerative diseases. Rodent models of Parkinson's disease are evaluated after specific intervention procedures (antioxidants, growth factors, immunomodulation). This work will establish the methodology for central nervous system - intervention strategies that can be used to restore functional brain activity in humans with neurodegenerative diseases.

A selected list of publications:

Melega WP, Lacan G, Gorgulho AA, Behnke EJ, De Salles AA   Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model PLoS ONE , 2012; 7(1): e30672, 1-8.
Yong J, Lacan G, Dang H, Hsieh T, Middleton B, Wasserfall C, Tian J, Melega WP, Kaufman DL   BCG vaccine-induced neuroprotection in a mouse model of Parkinson's Disease PLoS ONE, 2011; 6(1): e16610.
Lacan G, Plenevaux A, Rubins D, Way BM, Defraiteur C, Gillet S, Lemaire C, Aerts J, Luxen, A, Cherry SR, Melega WP.   Cyclosporine, a p-glycoprotein modulator, increases 18F-MPPF binding in rat brain and peripheral tissues: Micropet and ex vivo studies, Eur. J. Nuc. Med. Mol. Imaging, 2008; .
Chin MH, Qian W-J, Wang H, Petyuk VA, Bloom JS, Sforza DM, Lacan G, Liu D, Khan AH, Cantor RM, Bigelow DJ, Melega WP, Camp II DG, Richard D. Smith RD, Smith DJ.   miRNAs and codon usage regulate striatal gene and protein expression in two mouse models of Parkinson's disease, J Proteome Res, 2008; 7: 666-677.
Melega WP, Cho AK, Harvey DC, Lacan G   Methamphetamine blood concentrations in human abusers: application to pharmacokinetic modeling, Synapse, 2007; 61: 216-220.
O'Neil ML,Kuczenski R, Segal DS, Cho AK, Lacan G, Melega WP   Escalating dose pretreatment induces pharmacodynamic and not pharmacokinetic tolerance to a subsequent high-dose methamphetamine binge, Synapse, 2006; 60: 465-473.
Segal DS, Kuczenski R, O'Neil ML, Melega WP, Cho AK   Prolonged exposure of rats to intravenous methamphetamine: behavioral and neurochemical characterization, Psychopharmacology (Berl), 2005; 180: 501-512.
Segal DS, Kuczenski R, ONeil ML, Melega WP, Cho AK.   Escalating dose methamphetamine pretreatment alters the behavioral and neurochemical profiles associated with exposure to a high dose methamphetamine binge, Neuropsychopharmacology, 2003; 28: 1730-40.
Cho AK, Melega WP   Patterns of methamphetamine abuse and their consequences Journal of addictive diseases , 2002; 21(1): 21-34.
Segal, DS Kuczenski, R O'Neil, ML Melega, WP Cho, AK   Prolonged exposure of rats to intravenous methamphetamine: behavioral and neurochemical characterization Psychopharmacology, 2005; 180(3): 501-12.
Rubins, DJ Melega, WP Lacan, G Way, B Plenevaux, A Luxen, A Cherry, SR   Development and evaluation of an automated atlas-based image analysis method for microPET studies of the rat brain NeuroImage, 2003; 20(4): 2100-18.
Brown, VM Ossadtchi, A Khan, AH Yee, S Lacan, G Melega, WP Cherry, SR Leahy, RM Smith, DJ   Multiplex three-dimensional brain gene expression mapping in a mouse model of Parkinson's disease Genome research, 2002; 12(6): 868-84.
Cho, AK Melega, WP Kuczenski, R Segal, DS   Relevance of pharmacokinetic parameters in animal models of methamphetamine abuse Synapse (New York, N.Y.) , 2001; 39(2): 161-6.
Harvey, DC Lacan, G Tanious, SP Melega, WP   Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss Brain research. , 2000; 871(2): 259-70.
Cho, AK Melega, WP Kuczenski, R Segal, DS Schmitz, DA   Caudate-putamen dopamine and stereotypy response profiles after intravenous and subcutaneous amphetamine Synapse (New York, N.Y.) , 1999; 31(2): 125-33.
Melega, WP Cho, AK Schmitz, D Kuczenski, R Segal, DS   l-methamphetamine pharmacokinetics and pharmacodynamics for assessment of in vivo deprenyl-derived l-methamphetamine The Journal of pharmacology and experimental therapeutics, 1999; 288(2): 752-8.
Kuczenski R, Segal DS, Melega WP, Lacan G, McCunney SJ   Human methamphetamine pharmacokinetics simulated in the rat: behavioral and neurochemical effects of a 72-hour binge Neuropsychopharmacology, 2009; 34: 2430–2441.
Lacan Goran, Dang Hoa, Middleton Blake, Horwitz Marcus A, Tian Jide, Melega William P, Kaufman Daniel L   Bacillus Calmette-Guerin vaccine-mediated neuroprotection is associated with regulatory T-cell induction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease Journal of neuroscience research, 2013; 91(10): 1292-302.
Lacan Goran, Hadamitzky Martin, Kuczenski Ronald, Melega William P   Alterations in the striatal dopamine system during intravenous methamphetamine exposure: effects of contingent and noncontingent administration Synapse (New York, N.Y.), 2013; 67(8): 476-88.
Mulgaonkar Amit P, Singh Rahul S, Babakhanian Meghedi, Culjat Martin O, Grundfest Warren S, Gorgulho Alessandra, Lacan Goran, De Salles Antonio A F, Bystritsky Alexander, Melega William P   A prototype stimulator system for noninvasive Low Intensity Focused Ultrasound delivery Studies in health technology and informatics, 2012; 173(8): 297-303.