Development of Hsp90 Isoform-Selective Inhibitors as a Novel Opioid Dose-Reduction Therapy

Development of Hsp90 Isoform-Selective Inhibitors as a Novel Opioid Dose-Reduction Therapy is a research project anchored in translational pharmacology and drug discovery, positioned at the intersection of neuroscience, endocrinology and therapeutic development. The project builds on a longstanding research program focused on mechanisms of drug action, adverse events, and novel therapeutic discovery. 

The lab investigates pharmacologic mechanisms underlying central nervous system regulation of whole-body physiology and explores new strategies to improve safety and efficacy of existing therapeutics. Her prior work includes studies of opioid delivery and pharmacodynamics, exemplified by publications examining long-term morphine delivery and withdrawal, and broader interests in drug metabolism, pharmacology, and lead development. This project seeks to develop Hsp90 isoform-selective inhibitors as an approach to reduce required opioid doses while maintaining analgesic efficacy, thereby addressing clinical needs related to opioid safety.

The research emphasizes specificity at the isoform level to minimize off-target effects and adverse events, consistent with the lab’s focus on mechanisms of adverse events and enhancing drug target validation. Embedded in an environment that includes NIH-funded work and active involvement of undergraduate and graduate student researchers, the project integrates training with discovery. The initiative aligns with broader goals of improving therapeutic profiles of established analgesics by enabling dose reduction strategies that preserve analgesia but reduce the risk of tolerance, dependence, and other opioid-associated adverse outcomes. The project’s translational emphasis includes identification and validation of molecular mechanisms by which Hsp90 isoforms influence opioid receptor signaling or downstream pathways relevant to analgesia, as well as early-stage lead identification and characterization.  By focusing on isoform-selectivity and integrating rigorous target validation with lead development, the project aims to create safer adjunctive therapies that could lower opioid exposure in patients needing analgesia while mitigating long-term harms associated with higher opioid doses.