Michael F. Miles, M.D., Ph.D.
Department: Department of Pharmacology and Toxicology
Phone: (804) 827-4054
Fax: (804) 828-6432
Molecular Medicine Research Building, Room 6036
1220 East Broad Street
- M.D., Northwestern University, 1983
- Ph.D., Northwestern University, Ph.D., 1982
- Director and co-founder, VCU Alcohol Research Center
- Molecular mechanisms underlying role of prefrontal cortex in progressive ethanol consumption
- Role of Gsk3b in ethanol consumption and as a potential target for therapeutic intervention in alcohol use disorder
- Role of myelin-related gene expression in genetic risk for alcohol use disorder and ethanol-related brain or peripheral nerve pathology
- Genetics of ethanol induced analgesia (Co-PI with Imad Damaj)
The laboratory primarily seeks to understand underlying genetic risk factors and adaptive molecular mechanisms of brain plasticity occurring with abuse of alcohol in order to identify new targets for therapeutic intervention. In particular, gene networks are used to identify and study novel genes modulating behavioral responses to ethanol either with acute exposure or chronic consumption. Approaches used include advanced mouse genetics, genomics (RNAseq and microarrays), viral vector stereotactic delivery, cell and region-selective gene targeting, bioinformatics and behavioral pharmacology. We collaborate with colleagues within the VCU Alcohol Research Center (VCU-ARC) or Department of Pharmacology and Toxicology to validate and integrate our findings through behavioral pharmacology and cross-species studies with invertebrate models and human genetics.
Thibault, C, Lai, C, Wilke, N, Duong, B, Olive, MF, Rahman, S., Dong, H, Lockhart DF and Miles MF (2000) Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression. Mol Pharm 52:1593-1600.
Kerns, R, Ravindranathan, A, Hassan, S, Cage, MP, Sikela, JM and *MILES, MF (2005) Ethanol-responsive brain region expression networks: Implications for behavioral responses to acute ethanol in DBA/2J versus C57BL/6J mice. J Neurosci, 25:2255-1166.
Wolen, AR, Phillips, CA, Langston, MA, Putman, AH, Vorster, PJ, Bruce, NA, York, TP, Williams, RW and *MILES, MF (2012) Genetic dissection of acute ethanol responsive gene networks in prefrontal cortex: Functional and mechanistic implications. PLoS ONE 7(4): e33575. doi:10.1371/journal.pone.0033575. PMCID: PMC3325236
Hait, NC, Wise, LE, Allegood, JC, O'Brien, M, Avni, D, Reeves, TM, Knapp, PE, Lu, J, Luo, C, MILES, MF, Milstien, S, Lichtman, AH, and *Spiegel, S. (2014) Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory. Nat Neurosci 17(7):971-80. PubMed PMID: 24859201; PMCID: PMC4256678
Putman, AH, Wolen, AR, Harenza, J, Yordanova, RK, Webb, BT, Chesler, EJ, and *MILES, MF. (2016) Identification of quantitative trait loci and candidate genes for an anxiolytic-like response to ethanol in BXD recombinant inbred strains. Genes Brain Behav doi: 10.1111/gbb.12289. PubMed PMID: 26948279 PMCID: PMC4852167.
van der Vaart, AD, *Wolstenholme, JT, Smith, ML, Harris, GM, Lopez, MF, Wolen, AR, Becker, HC, Williams, RW, and MILES, MF. The allostatic impact of chronic ethanol on gene expression: A genetic analysis of chronic intermittent ethanol treatment in the BXD cohort. (2017) Alcohol 58:93-106. doi: 10.1016/j.alcohol.2016.07.010. Epub 2016 Nov 1. PubMed PMID: 27838001; PMCID: PMC5253248.
Bogenpohl, JW, Mignogna, KM, Smith, ML and *MILES, MF. Integrative analysis of genetic, genomic and phenotypic data for ethanol behaviors: a network-based pipeline for identifying mechanisms and potential drug targets. (2017) Methods in Molecular Biology 1488:531-549. PubMed PMID: 27933543; PMCID: PMC5152688.
^van der Vaart, A, Meng, X, Bowers, MS, Batman, AM, Aliev, F, Farris, SP, Hill, JS, Green, TA, Dick, D and COGA Consortium, Wolstenholme, JT, and *MILES, MF. Glycogen synthase kinase 3 beta regulates ethanol consumption and is a risk factor for alcohol dependence. (2018) Neuropsychopharmacology. doi: 10.1038/s41386-018-0202-x. [Epub ahead of print] PubMed PMID: 30188517; PMCID: PMC6224501. ^contributed equally
[This manuscript highlighted by the Editors of Neuropsychopharmacology in the commentary: “GSK3beta in the prefrontal cortex: a molecular handle specific to addiction pathology?” Neuropsychopharmacology 43, 2497–2498 (2018) PMID: 30310121]
^O’Brien, MA, ^Weston, RM Sheth, NU, Bradley, S, Bigbee, J, Pandey, A, Williams, RW, and *MILES, MF. Alterations to the synaptic transcriptome in response to ethanol-induced behavioral sensitization in DBA/2J mice. (2018) Front Genetics;9:402. doi: 10.3389/fgene.2018.00402. eCollection 2018. PubMed PMID: 30319688; PubMed Central PMCID: PMC6166094 ^contributed equally
Bogenpohl, JW, Smith, ML, Farris, SP, Dumur, CI, Lopez, MF, Becker, HC, *Grant, KA, and *MILES, MF. Cross-Species Co-analysis of Prefrontal Cortex Chronic Ethanol Transcriptome responses in mice and monkeys. (2019) Front Mol Neurosci 12:197. doi: 10.3389/fnmol.2019.00197. eCollection 2019. PubMed PMID: 31456662; PubMed Central PMCID: PMC6701453.
Mignogna, KM, Bacanu, SA, Riley, BP, Wolen, AR, and *MILES, MF. Cross-species alcohol dependence- associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data. (2019) PLoS One. 14(4):e0202063. doi: 10.1371/journal.pone.0202063. eCollection 2019. PubMed PMID: 31017905; PubMed Central PMCID: PMC6481773