Dr. Homanics’ laboratory is focused on understanding the molecular mechanism(s) of action of alcohol.  Despite being the most widely used and abused drug, it is largely unknown how alcohol exerts its effects on the brain to cause alcohol-induced behavioral changes.  If we could understand alcohol’s mechanism of action, we may ultimately be able to develop safe and effective treatments for preventing / combatting alcohol use disorders and alcoholism.

Two basic approaches are utilized by the Homanics laboratory for investigating alcohol action.  The first approach employs genetically engineered mice.  Mutant mice are created that harbor precise alterations in genes that encode putative alcohol targets.  The mutant mice are tested at the cellular, molecular, and whole animal levels for alterations in alcohol-induced responses.  The second approach utilizes molecular biology to investigate the epigenetic effects of alcohol on changes in gene expression.

Trainees in Dr. Homanics’ laboratory have the opportunity to use molecular biology and embryonic stem cell techniques to create genetically engineered mice.  Such mice are subsequently analyzed using molecular biology, pharmacology, histology, and numerous whole animal behavioral assays.  Studies of the epigenetic effects of alcohol action utilize chromatin immunoprecipitation, quantitative real time PCR, and western blotting techniques.  

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Important Publications

Blednov YA, CM Borghese, ML McCracken, JM Benavidez, CR Geil, E Osterndorff-Kahanek, DF Werner, S Iyer, A Swihart, NL Harrison, GE Homanics and RA Harris.  Loss of ethanol conditioned taste aversion and motor stimulation in knockin mice with ethanol-insensitive alpha2-containing GABA(A) receptors.  J Pharmacol Exp Ther 336:145-154, 2011.

Iyer SV, R Benavides, D Chandra, JM Cook, S Rallapalli, HL June and GE Homanics.  a4-containing GABAA receptors are required for antagonism of ethanol-induced motor incoordination and hypnosis by the imidazobenzodiazepine Ro15-4513.  Frontiers in Pharmacology 2:18, 2011.

Werner DF, A Swihart, V Rau, F Jia, CM Borghese, ML McCracken, S Iyer, MH Fanselow, I Oh, JM Sonner, EI Eger, NL Harrison RA Harris and GE Homanics.  Inhaled anesthetic responses fo recombinant receptors and knockin mice harboring alpha2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane.  J Pharmacol Exp Ther 336:134-144, 2011.

Chandra D, LM Halonen, AM Linden, P Procaccini, K Hellsten, GE Homanics and ER Korpi.  Prototypic GABA(A) receptor agonist muscimol acts preferentailly through forebrain high-affinity binding sites.  Neuropsychopharmacology 35:999-1007, 2010.

Werner DF, AR Swihart, C Ferguson, WR Lariviere, NL Harrison and GE Homanics.  Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive alpha1 GABA A receptors.  Alcohol Clin Exp Res 33:289-299, 2009.

Chandra D, DF Werner, RW Olsen, NL Harrison and GE Homanics.  Normal acute behavioral responses to moderate/high dose ethanol in GABAA receptor a4 subunit knockout mice.  Alcohol Clin Exp Res 32:10-18, 2008.

Glykys J, Z Peng, D Chandra, GE Homanics, CR Houser, I Mody. A novel naturally occuring GABAA receptor partnership with high sensitivity to ethanol. Nature Neuroscience 10:40-48, 2007.