Program 
Abstract
Genetic characterization of robust ethanol-responsive gene networks in mouse prefrontal cortex
 
Michael F. Miles, M.D., Ph.D.
Associate Professor
Departments of Pharmacology/Toxicology, Human Genetics and Neurology and the Center for Study of Biological Complexity
 
Identifying genes underlying or influencing complex traits such as alcoholism has been an extremely time-consuming and difficult task.  Despite the identification of hundreds of behavioral quantitative trait loci (QTL), very few cognate quantitative trait genes (QTG) have been robustly validated.  Recently, a number of laboratories have utilized the combination of behavioral genetics together with whole genome expression profiling across large genetic panels of animals to narrow the search for QTGs.  Such an approach still depends on the sensitivity, specificity and heritability of the behavioral data in order to connect phenotypes to genes.  As an alternative approach, our laboratory has performed a genetic analysis of genome-wide expression responses to acute ethanol in order to identify robust networks of ethanol-responsive genes. We identified genetic loci that influence ethanol regulation for networks of genes.  Several of these loci appear to have significant epistatic interactions, thus identifying an extended network of ethanol responders and potential mechanisms.  Our near term goal is to modulate these ethanol-response networks and then study consequent influences on ethanol evoked behaviors, thus going from gene network to behavior. 

 

Biosketch
Michael F. Miles, M.D., Ph.D.

Attended University of Notre Dame for undergraduate studies and Northwestern University for MD and Ph.D. degrees.  Postgraduate studies included a residency in Neurology and postdoctoral work with Richard Scheller in molecular neurobiology at Stanford University.

Faculty member in Neurology at University of California, San Francisco from 1987 until 1991, where worked at the Ernest Gallo Clinic and Research Center, a research center dedicated to studying the molecular neurobiology of alcoholism.  Joined VCU in August, 2001.

Since becoming a faculty member at UCSF, interests have focused on the molecular basis for brain plasticity seen with ethanol and other drugs of abuse.  Such plasticity is responsible for the development of behaviors such as tolerance, dependence and addiction.  In particular, studies have concerned the study of gene regulation at the transcriptional level by ethanol as a primary mechanism underlying brain molecular adaptations seen with alcoholism.