Chemist Receives $450,000 NIH Award to Study Critical Family of Enzymes

University of Arkansas / University Relations

Chenguang Fan

U of A biochemist Chenguang Fan has received a $450,000 grant from the National Institutes of Health to investigate the role of a specific family of enzymes in the formation of cancer.

By explaining the novel mechanisms of cancer formation, the project could help guide cancer treatment.

Fan's study is the first to look at the effects of lysine acetylation on human threonyl-tRNA synthetase, a family of essential enzymes for protein synthesis. These enzymes also play important role in regulating gene expression.

Lysine acetylation, the process of transferring acetyl-groups from acetyl-coA or acetyl-phosphate to lysine residues in proteins, leads to neutralizing lysine's electrostatic charge, thus affecting enzyme structures, functions and interactions.

Mutations of human threonyl-tRNA synthetase have been found in many human diseases, including mitochondrial diseases, neuropathies, a wide range of cancers and various infectious diseases. For this reason, the enzymes have been a target for drug development and medical therapies.

Human threonyl-tRNA synthetase's bacterial homologue has been known to be regulated by acetylation, so researchers hypothesize that lysine acetylation can also affect the human enzyme. To test this assumption, researchers in Fan's laboratory will identify the effects of lysine acetylation on the function and structure of threonyl-tRNA synthetase. They will also identify the impacts of its acetylation on both global translation and translation of oncogenic proteins and tumor suppressors in living cells.

As an Academic Research Enhancement Award for Undergraduate-Focused Institutions (AREA), the research team for this project is composed primarily of undergraduate students. Both well-established methods and new techniques will be applied in this project to strengthen undergraduate student research experience.