Stephanie Puig, Ph.D.
Assistant Professor of Pharmacology & Experimental Theraputics
Department of Pharmacology
Ph.D. University of Paris, Descartes, France
Dr. Puig’s research focuses on finding new therapeutic targets to improve safety of prescription opioids, by limiting the incidence of deleterious side effects such as tolerance, dependence, reward, and respiratory depression, in order to ultimately decrease the occurrence of addiction and overdoses death. She is particularly interested in understanding the molecular mechanisms and the circuitry involving receptor tyrosine kinase (RTK) signaling in opioid-mediated side-effects. Using a translational approach in rodents that combines behavioral neuropharmacology, mouse genetics, optogenetics, biochemistry, live cell, and tissue imaging, she aims at understanding the role of crosstalk between RTKs and the mu-opioid receptor (MOR, target of clinically prescribed opioids), in the signaling pathways activated by acute and chronic administration of prescription opioids in rodents. Using proteomics and phosphoproteomics, she is also interested in identifying novel druggable targets involved in the occurrence side-effects, downstream of MOR and RTKs signaling. Since opioids continue to being considered the most effective strategy to alleviate severe and chronic pain despite decades of research on alternatives, her work is primordial and could help thousands of patients currently taking prescription opioids and at risk for developing life-threatening side-effects or addiction.
Dr. Puig was recently awarded an R21 grant by the NIH NIDA to study the molecular mechanisms and circuitry specifically underlying peripheral opioid tolerance and involving keratinocytes and platelet-derived growth factor signaling.
Dr. Puig was recently selected as a Yale/NIDA Neuroproteomics Core center pilot grant awardee for her pilot project focusing on determining the signaling pathways activated by platelet-derived growth factor receptor beta upon opioid receptor activation by morphine in rodent models of tolerance and physical dependence.
Puig, S., Noble F., Benturquia N. Short- and long-lasting behavioral and neurochemical adaptations: relationship with patterns of cocaine administration and expectation of drug effects in rats. Transl. Psychiatry, 2012. 2: p. e175. DOI: 1038/tp.2012.103
Puig, S., Marie N. Benturquia N., Noble F. Influence of cocaine administration patterns on dopamine receptor regulation. Psychopharmacology (Berl), 2014. 231(16): p. 3131-7. DOI: 1007/s00213-014-3488-3
Geoffroy, H.A*. and Puig S.*, Benturquia N, Noble F. Temporal regulation of peripheral BDNF levels during cocaine and morphine withdrawal: comparison with a natural reward. Int. J. Neuropsychopharmacol, 2014. 18(5). DOI: 1093/ijnp/pyu088
Gutstein H and Puig S: F1000Prime Recommendation of [Kawasaki Y et al., Nat Med 2008 14(3):331-336]. In F1000Prime, 20 Jun 2013; 10.3410/f.1102342.793478348
Puig, S. and H.B. Gutstein, Opioids: keeping the good, eliminating the bad. Nat Med, 2017. 23(3): p. 272-273. DOI: 1038/nm.4277
Puig S. and Gutstein H.B. A “Tail” of opioid receptors. Journal of Clinical Investigation, 2017 Apr 3; 127(4):1221-1224. DOI: 1172/JCI93582
Lopez-Bellido R, Puig S., Huang P.J., Tsai C-R, Turner H.N., Galko M.J, Gutstein H.B. Growth factor signaling regulates mechanical nociception in flies and vertebrates. J Neurosci. 2019 May 28. pii: 2950-18. DOI: 1523/jneurosci.2950-18.2019
Puig S., Donica C.L., Gutstein, H.B. EGFR signaling causes morphine tolerance and mechanical sensitization in rats. eNeuro 28 February 2020, 7 (2) eNeuro.0460-18.2020; DOI: 1523/eneuro.0460-18.2020
Barkai, O.; Puig, S.; Lev, S.; Katz, B.; Eli-Berchoer, L.; Gutstein, H.B.; Binshtok, A. Platelet-derived growth factor activates nociceptive neurons by inhibiting M-current and contributes to inflammatory pain. Pain. 2019 Jun;160(6):1281-1296. DOI: 1097/j.pain.0000000000001523
Puig S., Barker K.E., Szott S.R., Kann P.T., Morris J.S. and Gutstein H.B. Spinal opioid tolerance depends upon platelet-derived growth factor receptor-β signaling, not mu-opioid receptor internalization. Under Molecular Pharmacology July 28, 2020, mol.120.119552. DOI: 1124/mol.120.119552
Deemyad, T.; Puig, S.; Papale, A; Qi, H.; LaRocca, G.M.; Aravind, D.; LaNoce, E.; Urban, N.N.; “Lateralized decrease of parvalbumin+ cells in the somatosensory cortex of ASD models is correlated with unilateral tactile hypersensitivity”. Cerebral Cortex. 2021 Aug 3;bhab233. DOI: 1093/cercor/bhab233
Howard-Quijano K, Yamaguchi T, Gao F, Kuwabara Y, Puig S, Lundquist E, Salavatian S, Taylor B, Mahajan A. “Spinal Cord Stimulation reduces Ventricular Arrhythmias by attenuating reactive gliosis and activation of spinal interneurons”. JACC Clin Electrophysiol. 2021 Aug 17; S2405-500X (21) 00527-2. DOI: 1016/j.jacep.2021.05.016
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