Summary of Current Research 

The ongoing research in my laboratory is focused on the genetic dissection of behavioral traits associated with risk for the development of alcohol and drug use disorders. Through both single gene and gene network analyses, our ultimate goal is to identify druggable targets for innovative and effective therapeutics. Our research utilizes genetic animal models to study simple and complex addiction-related traits. Some examples of simpler traits include acute stimulation and depression; changes in coordination; and altered body temperature. More complex traits include operant self-administration as a measure of drug reinforcement; voluntary free-choice consumption as a measure directly translational to human drug use; conditioned place preference as a measure of drug reward; conditioned taste aversion as a measure of sensitivity to aversive drug effects; and sensitization and tolerance as measures of behavioral and neural adaptation. In addition, some behaviors are measured to examine their co-morbidity with drug susceptibility measures, such as elevated zero maze, light:dark box, and open field behavior as measures of anxiety-like behavior; forced swim as a measure of depression-like behavior; and Morris water maze and novel object recognition as measures of cognitive ability. Mice with naturally-occurring genetic variants or engineered or selectively bred to possess genetic alterations are utilized in pharmacological, genetic mapping, and gene expression studies to identify mechanisms underlying differences in drug risk and response. We are currently focusing most of our attention on two drugs, alcohol and methamphetamine, due to my current directorship of the Portland Alcohol Research Center (PARC) and my past role as scientific director of the Methamphetamine Abuse Research Center (MARC).   

The genetic studies in my lab have the potential to identify common and unique genetic and neurochemical mechanisms underlying the motivational and neuroadaptive effects of addictive drugs. Genetic models we use include selectively bred mouse lines, panels of inbred strains, transgenic mice, knockout mice, recombinant inbred strains, and congenic strains. We recently utilized the services of the OHSU transgenic core to replace a mutated gene with the common form of the same and demonstrated reversal of several methamphetamine-related phenotypes in animals with this single gene change.

My laboratory collaborates with local and more distant investigators to enhance the scope of our research. For example, our collaborators have provided expertise in immunohistochemistry, radioligand binding assays, measures of immune function, electrophysiology, microdialysis, next generation sequencing for the global measurement of gene expression, and more. My laboratory also has an interest in the co-occurrence of drug use disorders. For example, we have performed several studies examining independent, compared to combined, alcohol and nicotine effects. These drugs are commonly co-abused and one reason for this may be that there are common underlying genetic mechanisms determining risk for addiction to the two drugs. Another possibility is that the drugs taken together create a stronger rewarding experience, or one drug reduces some of the negative consequences of the other. These are all hypotheses that we are exploring.  

Finally, our recent research has primarily been focused on methamphetamine, because of a unique genetic finding. We utilized selective breeding to create lines of mice with either high levels or low levels of voluntary methamphetamine intake. We then utilized DNA samples from these selected lines to map the locations of genes underlying genetic risk. Remarkably, we determined that a single gene, the trace amine-associated receptor 1 (Taar1) gene, accounts for >50% of the genetic variance in methamphetamine intake. We are currently performing research to determine other impacts of the spontaneously occurring mutation in this gene that results in production of a non-functional receptor and is associated with enhanced methamphetamine intake. There are polymorphisms in the human TAAR1 gene that may be relevant to risk for methamphetamine addiction. 

Previous Positions 

Postdoctoral Research Associate, Rutgers University

Assistant Professor, Department of Medical Psychology, OHSU

Associate Professor, Department of Behavioral Neuroscience, OHSU  

Non-Academic Interests 

Tennis