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Principal Investigator: TAMARA J. PHILLIPS
Organization: PORTLAND VA MEDICAL CENTER
Fiscal Year: 2024
Funding agency: Veterans Affairs
Project Summary/Abstract
Dr. Richards (Phillips) directs a research group within her laboratory, comprising a Senior Research Associate,
full-time laboratory technicians, a graduate student, and several summer interns. She also directs the
NIH/NIAAA-funded Portland Alcohol Research Center (PARC), which involves 14 research scientists and their
laboratory research personnel. The PARC is working toward the common goal of investigating the role of the
tetrapartite synapse, with components including the pre- and post-synaptic neuron, astroglial processes, and
the extracellular matrix (ECM), in risk for and the impact of chronic alcohol drinking. She has a research
component in the PARC and funded grants supporting methamphetamine (MA) research. Overall, her
laboratory develops and utilizes specialized genetic mouse populations, with the goal of understanding
multifaceted etiologies of risk for addiction and of identifying personalized treatments. The genetic mouse
populations model various aspects of addiction and are then subjected to in-depth study of the transcriptome,
single gene effects, genetically correlated behaviors and neural mechanisms. She studies multiple sensitivity
factors, including drug stimulant effects, reward, reinforcement, aversion, avoidance, cognitive factors, and
physiological correlates. Most recently, her work has placed a particular emphasis on resilient individuals with
strong genetic risk that do not choose high levels of drug intake. She believes that study of these individuals
will provide important information about opposing genes and mechanisms relevant to therapeutic development.
These protective effects are understudied in comparison to use-promoting rewarding drug effects. In fact,
human genetic studies do not include individuals who have experimented with a drug and found it to be
aversive, therefore avoiding its use. Nor have they delved into individual differences as much as population
effects (i.e., common is comparison of non-users and groups with use disorders). Dr. Richards' VA Merit
Review-funded research is focused on binge MA use and the impact of a single nucleotide polymorphism in
the trace amine-associated receptor 1 gene (Taar1m1J), discovered by her lab to account for 60% of the genetic
variance in voluntary MA intake in her selected line genetic animal model. Aims include identifying neurotoxic
effects of MA and the role of Taar1 variation in sensitivity to those effects; and identification of genetic
modifiers of the high risk, Taar1m1J/m1J genotype that predicts high levels of voluntary MA intake, using selective
breeding and transcriptomics. Her funded R01 grant was used to generate knock-in mice to prove that Taar1 is
a quantitative trait gene for MA intake and other MA traits that impact MA intake, including traits that index
sensitivity to MA reward and aversion. Recombinant inbred strains are being used to compare gene network
outcomes in mice that all possess the high risk Taar1m1J/m1J genotype, but exhibit different amounts of MA
intake. Targeted assessment of a potential interactive effect of the mu-opioid receptor gene (Oprm1) indicate
that Oprm1 allelic variation impacts the effect of Taar1 genotype on MA intake and other MA-related traits. Dr.
Richards' research project within the PARC is studying the risk transcriptome for alcohol preference using mice
selectively bred for high or low alcohol preference. She is also performing research designed to dissect
transcriptional differences associated with individual variation in response to genetic risk, by examining gene
expression networks in mice with differential levels of preference from the high alcohol preference line. Finally,
her research group is performing treatment-related research based on transcriptome findings, exploring new
pharmacotherapeutic avenues for alcohol use disorder.
Terms: <ARHGEF5><ARHGEF5 gene><Abstinence><Accounting><Alcohol Chemical Class><Alcohol dependence><Alcohols><Alleles><Allelomorphs><Amines><Animal Genetics><Animal Model><Animal Models and Related Studies><Armed Forces Personnel><Award><Behavioral Mechanisms><Biological Markers><Brain><Brain Nervous System><Breeding><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Candidate Disease Gene><Candidate Gene><Cas nuclease technology><Causality><Cell-Extracellular Matrix><Chemical Dependence><Chromosome 10><Chronic><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Cognitive><Collaborations><Combined Modality Therapy><Consumption><Crystal Meth><Crystal methamphetamine><Data><Deoxyephedrine><Desoxyephedrine><Differences between sexes><Differs between sexes><Disease><Disorder><Drug Addiction><Drug Controls><Drug Dependence><Drug Dependency><Drug usage><Drugs><ECM><Encephalon><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Etiology><Exhibits><Extracellular Matrix><Family><Funding><GEF5><Gene Expression><Genes><Genetic><Genetic Diversity><Genetic Models><Genetic Risk><Genetic Variation><Genetic predisposing factor><Genetic study><Genome><Genomics><Genotype><Goals><Grant><Health><Human><Human Genetics><Incentives><Individual><Individual Differences><Institution><Intake><Intervention><Intervention Strategies><Investigation><Investigators><KI mice><Knock-in Mouse><Laboratories><Laboratory Research><Laboratory Technicians><METH effect><METH use><Mechanisms of Behavior and Behavior Change><Medical><Medication><Mental disorders><Mental health disorders><Methamphetamine><Methylamphetamine><Mice><Mice Mammals><Military><Military Personnel><Modality><Modeling><Modern Man><Multimodal Therapy><Multimodal Treatment><Murine><Mus><N-Methylamphetamine><NIAAA><NIH><National Institute on Alcohol Abuse and Alcoholism><National Institutes of Health><Network Analysis><Opiates><Opioid><Outcome><P60><Pathway Analysis><Pharmaceutical Preparations><Pharmacological Treatment><Phenotype><Physiologic><Physiological><Population><Population Genetics><Postdoc><Postdoctoral Fellow><Process><Psychiatric Disease><Psychiatric Disorder><Psychiatry><Psychological reinforcement><Publications><Quantitative Genetics><R-Series Research Projects><R01 Mechanism><R01 Program><RNA Seq><RNA sequencing><RNAseq><Receptor Gene><Receptor Protein><Recombinant Inbred Strain><Reinforcement><Reporting><Research><Research Associate><Research Design><Research Grants><Research Personnel><Research Project Grants><Research Projects><Researchers><Rewards><Risk><Risk Factors><Role><Scientific Publication><Scientist><Sex Differences><Sexual differences><Single Base Polymorphism><Single Nucleotide Polymorphism><Stimulant><Study Type><Synapses><Synaptic><TIM1><Toxic effect><Toxicities><United States National Institutes of Health><Variant><Variation><Veterans><Work><addiction><addictive disorder><alcohol addiction><alcohol dependency><alcohol dependent><alcohol misuse><alcohol related research><alcohol research><alcohol use disorder><amine><behavior mechanism><bio-markers><biologic marker><biomarker><career><causation><chronic EtOH drinking><chronic alcohol consumption><chronic alcohol drinking><chronic alcohol ingestion><chronic alcohol use><chronic ethanol consumption><chronic ethanol drinking><chronic ethanol ingestion><combination therapy><combined modality treatment><combined treatment><contingency management><craving><customized therapy><customized treatment><develop therapy><differential expression><differentially expressed><disease causation><drug reward><drug use><drug/agent><early experience><epigenetically><ethanol misuse><ethanol research><ethanol use disorder><evidence base><gene network><genetic risk factor><global gene expression><global transcription profile><graduate student><high risk><human model><indexing><individual heterogeneity><individual variability><individual variation><individualized medicine><individualized patient treatment><individualized therapeutic strategy><individualized therapy><individualized treatment><inherited factor><intervention development><interventional strategy><knockin mice><mental illness><meth><meth abuse><methamphetamine abuse><methamphetamine effect><methamphetamine use><military population><model of animal><model of human><mouse model><mu opioid receptors><multi-modal therapy><multi-modal treatment><murine model><neural mechanism><neuromechanism><neuropsychiatric disease><neuropsychiatric disorder><neuropsychopharmacology><neurotoxic><patient specific therapies><patient specific treatment><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><pharmacologic><post-doc><post-doctoral><post-doctoral trainee><post-synaptic nerves><post-synaptic neurons><postsynaptic nerves><postsynaptic neurons><pre-synaptic nerve><pre-synaptic neurons><preference><presynaptic nerve><presynaptic neurons><programs><protective effect><psychiatric illness><psychologic><psychological><psychological disorder><psychosocial><receptor><research associates><resilience><resilient><response><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><single nucleotide variant><social role><study design><substance use><substance using><summer intern><summer internship><synapse><tailored medical treatment><tailored therapy><tailored treatment><therapeutic agent development><therapeutic development><therapy development><trait><transcriptional differences><transcriptome><transcriptome sequencing><transcriptomic sequencing><transcriptomics><treatment development><unhealthy alcohol use><unique treatment><μ opioid receptors><μ-OR><μOR>