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 including lncRNAs. The mutant mice are tested at the cellular, molecular, and whole animal levels for alterations in alcohol-induced responses. The second approach utilizes a variety of behavioral assaays and molecular techniques to investigate the epigenetic effects of alcohol on changes in gene expression and to explain effects of alcohol that persist across generations.
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 PCR, western blotting techniques, RNAseq, and numerous behavioral assays.
Blednov, Y.A., Borghese, C.M., Ruiz, C.I., Cullins, M.A., Da Costa, A., Osterndorff-Kahanek, E.A., Homanics, G.E., and Harris, R.A. (2017). Mutation of the inhibitory ethanol site in GABAA ρ1 receptors promotes tolerance to ethanol-induced motor incoordination. Neuropharmacology 123, 201-209.
Harris, R.A., Bajo, M., Bell, R.L., Blednov, Y.A., Varodayan, F.P., Truitt, J., de Guglielmo, G., Lasek, A.W., Logrip, M.L., Vendruscolo, L.F., et al. (2017). Genetic and pharmacologic manipulation of TLR4 has minimal impact on ethanol consumption in rodents. J Neurosci 37, 1139-1155.
Hill, S.Y., Rompala, G., Homanics, G.E., and Zezza, N. (2017). Cross-generational effects of alcohol dependence in humans on HRAS and TP53 methylation in offspring. Epigenomics 9, 1189-1203.
Homanics, G.E. (2018). Gene edited CRISPy Critters for alcohol research. Alcohol, In Press.
Rompala, G.R., Finegersh, A., Slater, M., and Homanics, G.E. (2017). Paternal preconception alcohol exposure imparts intergenerational alcohol-related behaviors to male offspring on a pure C57BL/6J background. Alcohol 60, 169-178.
Rompala, G.R., Mounier, A., Wolfe, C.M., Lin, Q., Lefterov, I., and Homanics, G.E. (2018). Heavy chronic intermittent ethanol exposure alters small noncoding RNAs in mouse sperm and epididymosomes. Frontiers in Genetics 9, 32.