Title: Unraveling the mechanisms of endogenous cell-cell signaling peptides
Abstract: Endogenous peptides (neuropeptides and peptide hormones) act as cell-to-cell signaling molecules to carry out complex tasks in living systems, including regulating metabolism, pain perception, stress response, circadian rhythm, and more. Characterizing the molecular mechanisms of endogenous peptides represents a significant goal to understand how living systems function in both healthy and disease states, and may identify novel therapeutic targets. Understanding cellular communication requires not only knowledge of the transmitter (i.e., the peptide ligand), but also information regarding the cognate receptor that mediates signaling on the partner cell. However, there exist a relatively large number of biologically active peptides whose cell-surface receptor(s) are not known, primarily because of a lack of techniques to reliably identify peptide receptors de novo.
To better understand the molecular mechanisms of intercellular communication, our group focuses on developing and utilizing chemical biology approaches to understand endogenous peptides and probe peptide-receptor interactions. One major project in the group is focused on developing methods to label neuropeptide receptors on the surface of living cells for the purpose of probing known peptide-receptor interactions and discovering novel receptors for bioactive peptides. We are also exploring the impact of an understudied endogenous peptide post-translational modification (L- to D-residue isomerization) on receptor recognition and signaling in nature. Overall, our research combines approaches from chemical biology, bioanalytical chemistry, and synthetic chemistry to advance our understanding of specific cell-cell signaling pathways, identify new pathways for further exploration, and provide innovative starting points for future therapeutics.
Bio: James Checco grew up in the Twin Cities, Minnesota and obtained his B.A. in Chemistry and Mathematics from St. Olaf College in 2010, and played clarinet in the St. Olaf Band. James received his Ph.D. in Chemistry from the University of Wisconsin-Madison in 2015 under the mentorship of Sam Gellman, where his research focused on developing methods to inhibit protein-protein interactions using non-natural peptide “foldamers”. After completing his Ph.D., James was a Beckman Institute Postdoctoral Fellow at the University of Illinois at Urbana-Champaign under the mentorship of Jonathan Sweedler, where he studied the molecular functions of neuropeptides.
In 2019, James joined the Department of Chemistry at the University of Nebraska-Lincoln, where his lab studies the molecular details of cell-to-cell communication by endogenous peptides. The ultimate goals of this research are both to understand fundamental processes in cellular communication and to identify novel targets for therapeutic intervention. The Checco lab has received funding from the NIH, NSF, and industry. In 2024, James earned a COBRE Rising Star Award from the National Association of IDeA Principal Investigators.
Keywords: Peptides, cell-cell signaling, mass spectrometry, chemical biology
Host: Professor Samuel Gellman