Nuclear Hormone Receptors and Regulation of Gene Expression

Understanding how gene expression is regulated in response to signals from both inside and outside the body plays a critical role in allowing us to adapt to changes in the environment. Importantly the genetic response to environmental signals is often disturbed in people with heart disease, infectious diseases, cancer, and diabetes. Research in our laboratory focuses on the regulation of gene expression by nuclear hormone receptors; a superfamily of DNA-binding transcription factors that turn on or turn off genes in response to the direct binding of small molecules.

Included in this superfamily are the well-known receptors for male and female sex hormones, however, other members of the superfamily regulate pathways that control metabolism. In particular, the liver x receptors (LXRalpha and LXRbeta) directly bind cholesterol metabolites that accumulate when cholesterol levels are high. In response to binding these ligands, LXRs regulate genes that control the body’s ability to transport and eliminate cholesterol. The laboratory employs a combination of state of the art techniques including genome-wide analysis of transcription, measures of gene expression in single cells, metabolite profiling and animal models of diseases. We believe that the combination of these approaches will provide an unprecedented look at regulation of gene expression in response to changes in diet and in the environment.