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Nokomis Ramos-Gonzalez, PhD

Ramos-Gonzalez PFDS24 Headshot
Postdoctoral Fellowship in Drug Discovery, 2024 Washington University in St. Louis

Exploring the Structural Basis for Efficacy and Ga Subtype Selectivity at the Kappa Opioid Receptor

Abstract

The most effective analgesics are drugs targeting the mu opioid receptor; yet, these have a battery of side effects including dependence, tolerance, euphoria and respiratory depression, leading to high abuse and overdose liability; there is a need for safer analgesics. We hypothesize that kappa opioid receptor drugs with low efficacy and reduced ß-arrestin recruitment may be the answer. We also propose to explore mechanisms of Ga subtype specificity at the kappa receptor as there is evidence from other class A GPCRs that Ga subtype selectivity can lead to reduced side effects. Ga subtype selectivity has not been fully explored at kappa and the underlying mechanism is unknown. We will explore this with a multidisciplinary approach to drug discovery: we will use in vitro, structural, computational, and biophysical techniques to explore the structural basis for decreased efficacy and ß-arrestin1/2 recruitment as well as Ga subtype specificity, and design new kappa opioid receptor drugs.

The PhRMA Foundation postdoctoral fellowship will allow me to drive my own research goals to further explore molecular and structural pharmacology. This fellowship will provide a fantastic platform to continue toward my goal of independent academic research.

Nokomis Ramos-Gonzalez

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