Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Berger, Shelley L.
Location University of Pennsylvania
Primary Field Medical Genetics, Hematology and Oncology
Secondary Field Cellular and Developmental Biology
 Election Citation
Berger is a leader in the field of eukaryotic gene regulation, unifying understanding of transcription and chromatin regulation. Her pioneering studies elucidated mechanisms of histone modifications, modifier enzymes, their complexes and their coordination. Her research has provided mechanistic understanding of histone and factor modifications in development, behavior, and cancer.
 Research Interests
Shelley Berger's laboratory is interested in chromatin mechanisms, and principally in histone and transcription factor post-translational modifications, in regulating transcription. Modifications include acetylation, methylation and ubiquitylation, and their combinations and antagonism provide an intricate gene regulatory language. Modifications are translated into emergent properties of normal physiology and disease, including cancer, senescence and aging, and control of memory and complex social behavior. In her laboratory, investigation of epigenetic regulation across this array of questions involves animal models encompassing budding yeast, human cells in culture, mouse, and eusocial ant. Wild type and mutant p53 utilize many chromatin enzymes and epigenetic pathways in normal and cancer cells; such enzymes provide robust, "druggable" targets. During aging there is broad epigenome dysregulation, including disruption of the nuclear lamina with associated chromatin domains, leading to tissue deterioration. Histone acetylation has a crucial role in regulating memory and behavior. Rapid and dynamic histone acetylation in brain neurons is powered by gene-located production of the co-factor acetyl-CoA to fuel acetylation enzymes to induce gene activation - as a potentially unique attribute of differentiated and nondividing cells. The histone acetylation landscape in the normal human aging brain reveals epigenetic protection compared to Alzheimer's disease. Histone acetylation critically alters ant brain function to instruct complex social behavior within the colony. ~

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