Development and Application of Nicotinic Acetylcholine Receptor Targeted Peptides for Biomedical Research

Our research focuses on nicotinic acetylcholine receptors (nAChRs), a diverse family of ligand-gated ion channels known for their role in modulating the release of central nervous system neurotransmitters and their involvement in brain disorders including addiction. Recent studies have highlighted their pivotal roles beyond the central nervous system, influencing significant disease processes such as peripheral neuropathic pain, inflammation, tumorigenesis, and stress-induced pathologies. Over the next five years, our goals include: • Developing a unique library of probes targeted to nAChR subtypes that lack selective ligands. We will accomplish this through structure-activity-relationship studies and mining the plethora of nAChR- targeted peptides refined over millions of years of evolution by carnivorous cone snails. • Exploiting existing ligands as tools to elucidate the structural, functional, and regulatory mechanisms of nAChRs. • Determining the functional role of nAChR subtypes in the pathophysiology of neuropathic pain states. Understanding this mechanism may offer ways to prevent pain development rather than merely masking symptoms and provide an alternative to opioid-based therapies. Our program addresses a critical need by providing potent, precision ligands that selectively target individual nAChRs. By creating highly selective probes and making them widely available to the research community, we will enable researchers to answer fundamental questions. These ligands will not only advance scientific understanding but also drive the development of new therapeutics, potentially serving as lead compounds for innovative treatments. Since specific subtypes of nicotinic receptors are utilized in a broad array of organs and tissues, the wider impact of our work may be felt across multiple fields, accelerating progress in both basic and applied research. Project Number: 1R35GM162026-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: J MCINTOSH | Institution: UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH, SALT LAKE CITY, UT | Award Amount: $500,500 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award B Study Section[MRAB] View on NIH RePORTER: https://reporter.nih.gov/project-details/11265929