Dr. Downes is a Staff Scientist in the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California. Dr. Downes has extensive experience spanning over 14 years of research in the nuclear receptor field. Early work centered on understanding the roles of nuclear hormone receptors (NHRs) in muscle differentiation and progressed to studying the molecular mechanism of NHR-mediated repression. Dr. Downes, in conjunction with Dr. Peter Ordentlich, isolated the first novel full-length clones of the co-repressor SMRT and an RNA-binding co-repressor associating factor, termed SHARP. Subsequent characterization of these co-repressors led to the identification of HDAC5 and HDAC7. Dr. Downes recently developed a novel chemical tool, termed fexaramine, as a specific agonist of the bile acid receptor FXR. The development of fexaramine allowed the determination of the first structure of the active conformation of the receptor, providing insight into the interactions of the natural low-affinity bile acid ligands. Dr. Downes received his PhD in Biochemistry at the University of Queensland, Australia.