Thomas E. Dever, Ph.D.

Senior Investigator

Section on Protein Biosynthesis

NICHD/DIR

6/228
6 Center Dr
Bethesda, MD 20892

301-496-4519

thomas.dever@nih.gov

Research Topics

Mechanism and Regulation of Eukaryotic Protein Synthesis

We study the mechanism and regulation of protein synthesis, focusing on GTPases, protein kinases, translation factors and mRNA features that control this fundamental cellular process. We use molecular-genetic and biochemical studies in yeast and human cells to dissect the structure-function properties of translation factors, elucidate mechanisms that control protein synthesis, and characterize how mutations in the protein synthesis apparatus cause human disease. Of special interest are the translation initiation factors eIF2, a GTPase that binds methionyl-tRNA to the ribosome, and eIF5B, a second GTPase that catalyzes ribosomal subunit joining in the final step of translation initiation. We also investigate stress-responsive protein kinases that phosphorylate eIF2alpha, viral regulators of these kinases, and how cellular phosphatases are targeted to dephosphorylate eIF2alpha. We are characterizing eIF2gamma mutations that are associated with MEHMO syndrome, a novel X-linked intellectual disability syndrome, and we are investigating the function of the translation factor eIF5A with a focus on its ability to stimulate the peptidyl transferase activity of the ribosome and facilitate the reactivity of poor substrates such as proline. We are also examining the role of the hypusine modification on eIF5A and the role of this factor in polyamine-regulated gene-specific translational control mechanisms.

Biography

Dr. Thomas Dever is head of the Section on Protein Biosynthesis in the Laboratory of Gene Regulation and Development of the NICHD, a position he has held since 1994. The Dever lab studies the mechanism and regulation of eukaryotic protein synthesis. Using a combination of yeast and mammalian molecular genetic, biochemical, and structural techniques they are gaining new insights into the process of cellular protein synthesis, dissecting the structure-function properties of the cellular factors that promote translation, elucidating mechanisms that control protein synthesis, and characterizing how mutations in the protein synthesis apparatus cause human disease. They are also studying viral regulators of the eIF2 alpha kinases in an effort to understand at the molecular level how these kinases regulate protein synthesis and how their activities can be modulated in response to environmental or developmental cues. Dr. Dever received his B.S. in Chemistry from Gannon University, Erie, Pennsylvania in 1984. He received his Ph.D. in Biochemistry in 1990 from Case Western Reserve University in Cleveland, Ohio where he initiated his studies on eukaryotic translation in the laboratory of Dr. Bill Merrick. He studied as a postdoctoral fellow in the laboratory of Dr. Alan Hinnebusch in the NICHD from 1990 to 1994. In addition to his research activities Dr. Dever serves on the editorial board of the journal Molecular Cell.

Selected Publications

  1. Ivanov IP, Shin BS, Loughran G, Tzani I, Young-Baird SK, Cao C, Atkins JF, Dever TE. Polyamine Control of Translation Elongation Regulates Start Site Selection on Antizyme Inhibitor mRNA via Ribosome Queuing. Mol Cell. 2018;70(2):254-264.e6.

  2. Shin BS, Katoh T, Gutierrez E, Kim JR, Suga H, Dever TE. Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis. Nucleic Acids Res. 2017;45(14):8392-8402.

  3. Gutierrez E, Shin BS, Woolstenhulme CJ, Kim JR, Saini P, Buskirk AR, Dever TE. eIF5A promotes translation of polyproline motifs. Mol Cell. 2013;51(1):35-45.

  4. Skopkova M, Hennig F, Shin BS, Turner CE, Stanikova D, Brennerova K, Stanik J, Fischer U, Henden L, Müller U, Steinberger D, Leshinsky-Silver E, Bottani A, Kurdiova T, Ukropec J, Nyitrayova O, Kolnikova M, Klimes I, Borck G, Bahlo M, Haas SA, Kim JR, Lotspeich-Cole LE, Gasperikova D, Dever TE, Kalscheuer VM. EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO. Hum Mutat. 2017;38(4):409-425.

  5. Borck G, Shin BS, Stiller B, Mimouni-Bloch A, Thiele H, Kim JR, Thakur M, Skinner C, Aschenbach L, Smirin-Yosef P, Har-Zahav A, Nürnberg G, Altmüller J, Frommolt P, Hofmann K, Konen O, Nürnberg P, Munnich A, Schwartz CE, Gothelf D, Colleaux L, Dever TE, Kubisch C, Basel-Vanagaite L. eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation. Mol Cell. 2012;48(4):641-6.


This page was last updated on October 25th, 2018