The National Institutes of Health awarded Chenguang Fan, an associate professor of chemistry and biochemistry at the University of Arkansas, $562,500 to investigate the impact of lysine aminoacylation, a chemical modification of metabolism-driven proteins, on cellular metabolism. This research could reveal the mechanisms behind this chemical modification, tools for studying it, and its role in diseases such as cancer.

Lysine aminoacylation is a chemical modification of lysine, an amino acid in proteins. It acts like a fine-tuning switch for a cell's metabolism, much like adding an attachment to a tool can modify how it functions. This chemical modification is one way a cell can rewire proteins in response to metabolic changes, and when that wiring goes awry, it can lead to major diseases. Fan says, "It's a novel type of protein modification, and its role in human health remains largely unknown. It has been found in the tumor tissues of liver cancer patients and human kidney cancer cells, indicating the potential association with cancers."

Fan and his lab have established orthogonal translation systems (OTS), which are custom protein-making machinery, for four types of aminoacylation, paving the way for genetic code expansion (GCE) testing. GCE is a way for scientists to upgrade a cell's protein-making instructions so it can include new building blocks in proteins. "In this project, we use GCE to bypass a cell's naturally existing modification pathway to artificially produce proteins with lysine aminoacylation, thus making investigation of the chemical process much easier," says Fan.

This work is a complementary fit for Fan's lab, whose research focus includes protein chemistry, bacterial pathogenesis, cancer biology, and synthetic biology. Fan says, "One of my lab's major research directions is to use the genetic code expansion technique to study protein modifications in both bacteria and humans."  His goal is to provide evidence of the role of lysine aminoacylation in regulating metabolism in human cells, and to develop tools that his lab and other researchers in this field can use to study this chemical modification.  Lysine is often a "hotspot" for protein regulation, and modifying it can signal changes in a protein's stability, its location in the cell, and the molecules it interacts with. When the lysine aminoacylation process goes wrong, it has been linked to conditions like cancer, metabolic disorders, and neurodegenerative diseases. Since it is reversible, there is potential to target it with drugs to restore healthy protein function.

Prior to receiving this award, Fan was a Research Project Leader (RPL) with the Arkansas Integrative Metabolic Research Center. His research as an RPL investigated the role of phosphorylation, or protein modification, of isocitrate dehydrogenase (IDH) in breast cancer. While his new project is different from his RPL research, both projects involve investigating protein modifications that serve a similar purpose - regulating metabolism by tweaking proteins - and the role these modifications play in diseases of cell and tissue metabolism, which is a key focus of the AIMRC. Fan says, "My experience as a Research Project Leader with the AIMRC enabled me to refocus my research to cell metabolism, and it provided me with sufficient expertise and ample preliminary results for this project."

The AIMRC was founded in 2021 by Kyle Quinn with support from the University and an NIH Centers of Biomedical Research Excellence (COBRE) award. It is now led by Narasimhan Rajaram, a professor of biomedical engineering, who became the center director in the summer of 2025.

The AIMRC has established research cores specializing in bioenergetics, imaging and spectroscopy, and data science to aid campus researchers like Fan. By combining technical expertise and providing access to advanced equipment in these core areas, along with a cross-disciplinary faculty development and mentoring program, the AIMRC aims to foster a cohort of independent researchers with federally funded projects related to metabolism.

For more information on becoming an AIMRC Project Leader, or for other AIMRC funding opportunities, please visit the center website at or contact Kimberley Fuller at fullerk@uark.edu