Endocrine Abstracts

Dr Hager received his PhD in Genetics at the University of Washington, and pursued postdoctoral studies with Dick Epstein at the Institut de Biologie Moleculaire in Geneva and with Dr William Rutter at the University of California-San Francisco. After moving to the NIH, he developed the mouse mammary tumor virus (MMTV) system as a model to study hormonal regulation of gene expression, and utilized this system to describe the first known hormone responsive sequences. He reported the first evidence that nucleosomes were positioned at specific sites across a regulatory region, and showed that nucleosome reorganization was central to the mechanism of glucocorticoid receptor (GR) action, the first formal argument that nucleoprotein transitions were involved in gene regulation by nuclear receptors.

In 2000, Dr Hager and colleagues reported the first direct observation of a transcription factor binding to an authentic regulatory sequence in living cells. Using this system, he discovered that the GR undergoes rapid exchange with regulatory elements in the continued presence of ligand, developing the ‘hit-and-run’ hypothesis for transcription factor action. This highly unexpected development challenged the classic view of transcription factors as statically bound to regulatory elements, and opened a new paradigm in the study of gene regulation.

Dr Hager has been extensively involved in genome wide characterization of epigenetic states, and the dynamics of chromatin transitions. He demonstrated that several transcription factors fail to produce footprints incellular chromatin because of their brief residence times, and developed the concept of ‘dynamic assisted loading,’ a mechanism central to regulatory element function. This concept combines data from genome wide factor localization studies, investigation of chromatin remodeling factors, and real time dynamic studies in living cells.

Dr Hager is currently Chief of the Laboratory of Receptor Biology and Gene Expression, and Chair of the Center of Excellence in Chromosome Biology at the NCI.