James Checco

James Checco is Associate Professor of Chemistry at the University of Nebraska–Lincoln, where his group asks how endogenous peptides carry messages between cells and which molecular details decide the receptor that hears them. Neuropeptides and peptide hormones underlie physiology and behavior across the animal kingdom, yet for many of them the receptor is unknown and the basis of recognition is uncharted.

Much of his work centers on an understudied post-translational modification: the enzyme-catalyzed isomerization of a single L-residue to its D-form. Because the change leaves the mass untouched, D-amino acid-containing peptides are nearly invisible to standard peptidomic workflows. In 2023 his group showed that in the Aplysia allatotropin-related peptide system, the stereochemistry of one residue steers the neuropeptide between two distinct G protein-coupled receptors. They identified a new receptor selective for the D2 form, which carries a single D-phenylalanine, and established isomerization as a natural switch for receptor selectivity, a mechanism other neuropeptide systems may well share.

Questions like these depend on finding receptors in the first place, and the lab builds chemical tools for that problem, including affinity-driven aryl diazonium chemistry that labels peptide receptors on the surface of living cells. The group combines chemical peptide synthesis, mass spectrometry and cell-based signaling assays. With hibernation biologist Matthew Andrews, Checco has used quantitative peptidomics to follow seasonal changes in neuropeptides and peptide hormones in the hypothalamus and pituitary of the thirteen-lined ground squirrel, work with implications for organ preservation and obesity.

Checco earned a B.A. in chemistry and mathematics at St. Olaf College and a Ph.D. in 2015 at the University of Wisconsin–Madison with Samuel Gellman, designing non-natural peptide foldamers to inhibit protein–protein interactions. As a Beckman Institute Postdoctoral Fellow at the University of Illinois Urbana-Champaign with Jonathan Sweedler, he turned to the functions of D-amino acid-containing neuropeptides. He joined Nebraska in 2019, where he is also a project leader in the Nebraska Center for Integrated Biomolecular Communication. In 2024 he received a COBRE Rising Star Award from the National Association of IDeA Principal Investigators, and his teaching has earned a College of Arts and Sciences Distinguished Teaching Award.

His path, from designing peptides that nature never made to decoding the ones it does, makes him a natural voice for the symposium’s theme of connecting chemistry and biology.