Alan G. Hinnebusch

National Institutes of Health


Election Year: 2015
Primary Section: 26, Genetics
Membership Type: Member

Biosketch

Alan Hinnebusch is a molecular geneticist recognized for his work on mechanisms controlling gene expression at the translational and transcriptional levels. He is particularly known for elucidating a dual regulatory response to nutrient starvation and stress involving the phosphorylation of translation initiation factor 2, which induces translation of transcription factors via short upstream open-reading-frames in their mRNAs while suppressing the translation of most genes. Hinnebusch was born in Pittsburgh, Pennsylvania in 1954 and grew up outside of Pittsburgh (Monroeville) and later in Canton, Ohio. He graduated from the University of Dayton with a degree in biology in 1975 and from Harvard University in 1980 with a PhD in biochemistry and molecular biology. He was a postdoctoral fellow studying yeast genetics with Gerald R. Fink, first at Cornell University and later at M.I.T., and became an independent investigator at the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health in Bethesda, Maryland in 1983. He is also a fellow of the American Academy of Microbiology, the American Association for the Advancement of Science, and the American Academy of Arts and Sciences.

Research Interests

Alan Hinnebusch's laboratory investigates the process of translation initiation and mechanisms of general and gene-specific translational control, and the molecular basis of transcriptional activation and its role in nutrient control of gene expression, by exploiting the powerful genetic system of budding yeast Saccharomyces cerevisiae. His laboratory elucidated the mechanism of translational control by eIF2 phosphorylation via upstream open reading frames in mRNAs, and is currently focused on the general mechanism of translation initiation, including recruitment of initiator tRNA and mRNA to the ribosome, ribosomal scanning of the mRNA, and accurate recognition of the AUG start codon. The roles of RNA helicases and accessory proteins in determining translational efficiencies genome-wide, and the structure and regulation of the eIF2 kinase Gcn2, also are under study. In the area of transcriptional control, his group helped to define the structure of transcriptional activation domains and their roles in cofactor recruitment, functions of cofactors in assembly of initiation complexes and transcription elongation, and cyclin-dependent kinases that phosphorylate RNA Polymerase II during the transcription cycle. They are currently focused on identifying the co-factors responsible for the remodeling and eviction of nucleosomes from gene promoters, as a key step in transcriptional activation, throughout the genome.

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