Molecular Biosciences

Research Summary: 

Our group studies the genetic determinants of common heritable disorders including: schizophrenia, autism, anxiety disorder, bipolar disorder, Alzheimer s disease and cardiovascular disease. We are interested in novel genomic and bioinformatic approaches to realize this goal, and when possible, we use mouse models to inform the search for human disease genes. In the study of human anxiety disorders, for example, we study a well-characterized fear-related phenotype, fear conditioning, in both humans and in mice. Short term selective breeding paradigms are used to generate phenotypic extremes for fear conditioning, to map quantitative trait loci, and to explore alterations in gene expression related to fear-conditioning. Trait-related genes identified from such studies are then genotyped in a random human population scored for attributes of fear conditioning to identify human trait alleles, which, in turn are genotyped in families segregating several different anxiety disorders. In collaboration with computational scientists, we are using similar strategies to predict and evaluate pathway candidate genes in the study of atherogenic lipid profiles related to cardiovascular disease, and in the study of Alzheimer s disease and age-related memory loss. In all these studies the common goal is to (1) harness the vast stores of information embedded in the DNA sequence of scores of organisms including the human, (2) use animal models to inform the human studies, (3) explore heritable endophenotypes to focus and simplify the search for disease-related genetic determinants, and (4) integrate these various approaches in a standardized and systematic way to optimize the search for genetic determinants of common genetic disorders.