Two overarching themes unite the Portland Alcohol Research Center (PARC) projects and cores. The first is genetic and epigenetic risk factors that contribute to the etiology of alcohol use disorders. The second is the role of genetic and epigenetic factors in the consequences of alcohol use. A major strength is the use of multiple species, which will result in more comprehensive analysis and provide important translational links. A significant focus is on neural mapping via imaging studies in non-human primates and humans, and brain region-specific gene expression studies in mice and macaques. Importantly, we retain our focus on genetic influences on level of chronic alcohol use and neuroadaptation in mice and monkeys, and also introduce a human Project (P001) that will consider genetic family history and brain response to an acute alcohol challenge. We expand our explorations to consideration of the impact of alcohol use on epigenetic marks and consequences for host gene expression. The genetic risk and protective markers, patterns of neural circuitry differences and changes, and epigenetic and gene network information will ultimately help us and others to develop strategies for the prevention and treatment of alcoholism. Our existing genetic and imaging network analyses in mice and/or non-human primates have provided important information about relevant brain regions and pathways, and important gene networks and hubs. This information provides the basis for validation steps to now be undertaken in a new Core (C001) designed for that purpose; C001 will also develop new approaches to study nominated neural mechanisms and pathways as they arise. Four research Projects (P001-P004), two service Cores (C001, C002), and a pilot project Core (C003) address the PARC themes, using mouse models, non-human primates and human subjects. An example of a proposed pilot project is one that will supplement circuit information arising from our expanded focus on imaging in non-human primates and humans, by further developing our ability to perform imaging in mice. An outreach Core (Information Dissemination Core, C004) continues to train pre-doctoral, post-doctoral and medical students in alcohol research, disseminates research findings to the public, and engages in a range of educational activities with elementary to high school students. Our bioinformatics efforts have enabled expansion of a key strength of our group from the analysis of the contributions of individual genes on behavioral functions of the whole organism to include gene network identification; this will continue in Core (C002). In addition, the PARC has an extensive network of collaborations with alcohol researchers at other institutions, including those linked to other Centers and consortia. In summary, the PARC seeks to identify genetic factors and epigenetic changes that place individuals at risk or protect them from alcoholism, and to identify genetic, epigenetic and neural consequences of excessive alcohol use. This knowledge will facilitate intervention and the development of better therapeutics to treat alcohol use disorders.

Public Health Relevance

The Portland Alcohol Research Center seeks to identify genetic and epigenetic factors that place individuals at risk or protect them from alcoholism, and to identify genetic, epigenetic and neural consequences of excessive alcohol use. This knowledge will facilitate intervention and the development of better therapeutics to treat alcohol use disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA010760-22
Application #
9201279
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Parsian, Abbas
Project Start
1996-12-01
Project End
2020-12-31
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
22
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Aoun, E G; Jimenez, V A; Vendruscolo, L F et al. (2018) A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans. Mol Psychiatry 23:1466-1473
Colville, Alexandre M; Iancu, Ovidiu D; Lockwood, Denesa R et al. (2018) Regional Differences and Similarities in the Brain Transcriptome for Mice Selected for Ethanol Preference From HS-CC Founders. Front Genet 9:300
Xu, Ting; Falchier, Arnaud; Sullivan, Elinor L et al. (2018) Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo. Cell Rep 23:429-441
Iancu, Ovidiu D; Colville, Alexander; Walter, Nicole A R et al. (2018) On the relationships in rhesus macaques between chronic ethanol consumption and the brain transcriptome. Addict Biol 23:196-205
Morales, Angelica M; Jones, Scott A; Ehlers, Alissa et al. (2018) Ventral striatal response during decision making involving risk and reward is associated with future binge drinking in adolescents. Neuropsychopharmacology 43:1884-1890
Gavin, David P; Hashimoto, Joel G; Lazar, Nathan H et al. (2018) Stable Histone Methylation Changes at Proteoglycan Network Genes Following Ethanol Exposure. Front Genet 9:346
Purohit, Kush; Parekh, Puja K; Kern, Joseph et al. (2018) Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice. Alcohol Clin Exp Res 42:879-888
Müller-Oehring, Eva M; Kwon, Dongjin; Nagel, Bonnie J et al. (2018) Influences of Age, Sex, and Moderate Alcohol Drinking on the Intrinsic Functional Architecture of Adolescent Brains. Cereb Cortex 28:1049-1063
Iancu, Ovidiu Dan; Colville, Alex M; Wilmot, Beth et al. (2018) Gender-Specific Effects of Selection for Drinking in the Dark on the Network Roles of Coding and Noncoding RNAs. Alcohol Clin Exp Res :
Kafkafi, Neri; Agassi, Joseph; Chesler, Elissa J et al. (2018) Reproducibility and replicability of rodent phenotyping in preclinical studies. Neurosci Biobehav Rev 87:218-232

Showing the most recent 10 out of 291 publications