Ryan Gumpper received his PhD in Chemistry from Georgia State University where he studied the structural biology of negative-stranded RNA viruses. After his PhD, Ryan spent a short time working as a data scientist in the tech industry, where he refined his computational skills. In May of 2020, Ryan began his postdoc in Bryan Roth’s lab in the Department of Pharmacology at UNC Chapel Hill, where he worked on a wide array of projects related to G-protein coupled receptors. During his postdoc, Ryan used a combination of pharmacological, computational, and structural biology techniques to characterize the molecular mechanisms of DREADDs, taste receptors, and serotonin receptors, to name a few. Beginning in 2023, Ryan began as the project manager of a large DARPA project in the Roth lab, which is developing non-hallucinogenic 5-HT2A agonists for the treatment of depression. In July 2024, Ryan was able to stay in Chapel Hill and became an Assistant Professor in the Division of Chemical Biology and Medicinal Chemistry in the Eshelman School of Pharmacy, officially beginning his lab. The Gumpper lab is driven by a singular goal: to understand how molecular interactions between psychedelic compounds and their receptors inform their downstream biological effects.

X: @rgumpper

Linked-in: https://www.linkedin.com/in/rgumpper/

Website: https://tarheels.live/gumpperlab/

The structural diversity of psychedelic drug actions revealed

There is currently a resurgence in exploring the utility of classical psychedelics to treat depression, addiction, anxiety disorders, cluster headaches and many other neuropsychiatric disorders. The biological target of these compounds, and a hypothesized target for their therapeutic actions, is the 5-HT2A serotonin receptor. Here we present 7 new cryo-EM structures covering all major compound classes of psychedelic and non-psychedelic agonists including a novel β-arrestin biased compound RS130-180. Identifying the molecular interactions between various psychedelics and the 5-HT2A receptor reveals both common and unique motifs among the examined psychedelic chemotypes. These findings lead to a broader mechanistic understanding of 5-HT2A activation, which has catalyzed the development of novel chemotypes with the potential for therapeutic utility and fewer side-effects.