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Puig Lab Research


The Puig lab uses rodent preclinical models to study mechanisms of opioid signaling. We focus on understanding molecular mechanisms and neuronal circuitry that mediate opioid side-effects. Our goal is to identify new therapeutic targets to increase opioid safety and prevent opioid use disorders (OUD).

Check out our recent publications

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Projects

The Puig Lab is currently interested in the role that Receptor Tyrosine Kinases (RTKs) play downstream of the Mu-opioid receptor (MOR) to mediate side-effects.

Examining cellular mechanisms and circuitry underlying RTK-mediated opioid tolerance
We discovered that PDGFRβ acts as a core signaling effector mediating tolerance to all opioids used in the clinic (Puig et al, Molecular Pharmacology, 2020). However, the precise molecular mechanisms and the neural circuitry underlying PDGFRβ-mediated tolerance remain completely unknown. We are using rodent behavioral pharmacology, mouse genetic, biochemistry, molecular biology, and spatial biology to understand the in vivo mechanisms and circuitry mediating central and peripheral tolerance.

Identifying signaling pathways downstream of RTK that mediate opioid tolerance
This project uses proteomics, phosphoproteomics and transcriptomics to identify signaling pathways and differentially expressed genes/proteins downstream of RTK upon opioid activation. This study will help outline molecules and signaling pathways that may be mediating opioid side-effects through RTK signaling. 

Preclinical studies of RTK involvement in opioid reward and OUD
In pilot studies, we found that RTKs can modulate opioid reward. This project will involve rodent behavioral pharmacology, rodent genetics, high-plex tissue imaging to understand the mechanisms and circuits underlying RTK modulation of reward and the potential role in OUD development.

Examining the molecular mechanisms of MOR-RTK crosstalk using a live-cell approach.
These studies will focus on understanding the molecular mechanisms by which opioid-activated MOR recruit RTK signaling and how consequential signaling pathways my impact canonical MOR signaling effectors to induce side-effects. This in vitro project involves cell culture, biochemistry, molecule tagging and cellular transfection, live cell imaging, high-resolution microscopy. 

Interested in collaborating or joining the lab to contribute to these projects?

Contact Stephanie Puig today!