Defining JNKs: Targets for drug discovery

“If you are going to be successful as a scientist, you want to have fun while you do it,” Roger Davis said, reflecting on the curiosity and enthusiasm that have fueled his four decades in research.

Roger Davis

After earning his Ph.D. at the University of Cambridge, Davis moved to the United States and has spent the past 40 years as a professor at the University of Massachusetts Chan Medical School.

A pioneer in defining Jun N-terminal kinase, or JNK, Davis is being honored with the American Society for Biochemistry and Molecular Biology's Bert and Natalie Vallee Award in Biomedical Science, recognizing his discovery of this signaling protein and the decades of insight that followed.

In his letter of support, Michael P. Czech, also a professor at UMass Chan, wrote, “The discovery of JNK by Davis has had enormous impact, leading to him being the most highly cited scientist in all fields subsequent to the discovery … Honoring the discovery of JNKs is deserving … and will be well received by basic biomedical scientists across the globe.”

Davis’s lab is best known for studying stress signaling. “We came into this from basic biochemistry and protein phosphorylation, identifying sites of phosphorylation and mutating them to understand function,” he said. A strange proline-directed phosphorylation site with two prolines caught their attention, leading to further work exploring MAP kinases and eventually the initial cloning of the Jun kinases, followed by work on p38 MAP kinases.

Initially, scientists thought JNK was oncogenic, but Davis’s work revealed that it can also act as a tumor suppressor, depending on the tumor microenvironment.

“It is exciting that there may be a way to use the role of JNK in the tumor microenvironment to develop therapies against cancer,” Davis said.

In other diseases, JNK signaling affects communication among organs such as the brain, liver, and fat tissue, influencing satiety, metabolism and inflammation in type 2 diabetes.

“There’s this intricate crosstalk,” Davis said. “And we’re just beginning to figure out how JNK fits into it.”

Davis and his team showed that JNK is not a single protein but a family encoded by three genes, diversified through a process called alternative splicing. In some tissues, this can produce up to 10 isoforms.

At the 2026 ASBMB Annual Meeting, Davis will present his work showing that swapping exon 7a or 7b changes the shape of JNK’s docking site, determining which proteins it interacts with and ultimately altering the signaling output.

“We have really good mouse models to study where we can control the splicing genetically and force the kinase in specific cell types to include only exon 7a or 7b,” Davis said. “If you can more precisely target the spliced isoform that’s mediating the biology you’re studying, I think we may have more selective and better drugs.”

Despite his many awards and honors, Davis is quick to credit his trainees. “Very little of the work was done by me,” he said. “It’s the students and postdocs. They did science, and many have gone on to lead labs of their own.”