Jenny Wilkerson Laboratory
About Us
Our work centers around the principles of behavioral pharmacology to answer pressing drug discovery and novel compound development questions.
Aberrant inflammation is a driving factor in many disease states including pathological pain, cancer, neurodegenerative disease, mood disorders, and drug abuse/dependence. The work done in our laboratory investigates novel compound pharmacology and therapeutic implications. We specifically focus on compounds to treat inflammation-driven diseases and diseases associated with inflammation, such as pathological pain, cancer, neurodegenerative disease, mood disorders, and drug abuse/ dependence.
Many natural products such as Cannabis sativa, Mitragyna speciosa (kratom), and the numerous compounds contained in these and other natural products have either known or speculated medicinal use. Indeed, nature has provided humankind a proverbial medicine chest of potential therapeutics. A number of natural products may be useful to modulate the immune system and are waiting to be developed as therapeutics. Another major focus of our laboratory is natural product therapeutic development and pharmacological investigation, as well as abuse liability and untoward side effect examination.
Research Interest
|
The Team
Yuma Ortiz Ph.D. Candidate/ |
Julio Zuarth Gonzalez Graduate Student/ |
Kofi Frimpong-Manson Graduate Student / |
Chanel Mercurius Research Aide |
Alexandria Ragsdale Research Aide |
Billy Lee Research Aide |
Leila Shamir Research Aide |
- Project #: DA047855-A1
Funding Agency: NIH/National Institute on Drug Abuse
Kratom alkaloids: in vitro and in vivo pharmacological mechanisms
04/01/2019 – 03/31/2024
Role: Co-Investigator (MPI: Dr. Chris McCurdy, PI: Lance McMahon)
Total Costs: $3,626,856
Grant detail: The major goals of this project are to determine the in vitro and in vivo pharmacological interactions among kratom alkaloids to include ADME and behavioral/physiological effects (drug discrimination, self-administration). - Project #: UH3DA048353
Funding Agency: NIH/National Institute on Drug Abuse
Opioid use disorders: UF Pharmacy medications discovery and development
12/15/2020 – 11/30/2023
Role: Co-Investigator (MPI: Dr. Chris McCurdy, PI: Lance McMahon)
Total Costs: $4,754,180
Grant detail: The major goals of this project are to initiate a drug discovery and development effort aimed at kratom alkaloid derivatives as new medications for pain and opioid dependence pharmacotherapy. New chemical entities will be derived from a mitragynine scaffold, and in vitro and in vivo pharmacological mechanisms will be explored, to include binding, efficacy, stability, ADME, and behavioral/physiological effects (drug discrimination, self-administration, respiratory depression, and dependence).
- 38. Hiranita, T.; Obeng, S.; Sharma, A.; Wilkerson, J.L.; McCurdy, C.R.; McMahon, L.R. (2022). In vitro and in vivo pharmacology of kratom. Advances in Pharmacology, Academic Press
- 37. Wilkerson, J.L.; Hiranita, T.; Koek, W.; and McMahon, L.R. (2022). The
discriminative stimulus effects of baclofen and gamma hydroxybutyrate in C57BL/6J mice. Behav Pharmacol, 33(6), 427–434. - 36. Obeng, S.; León, F.; Patel, A.; Zuarth Gonzalez, J.D.; Da Silva, L.C.; Restrepo,
L.F.; Gamez-Jimenez, L.R.; Ho, N.P.; Guerrero Calvache, M.P.; Pallares, V.L.; Helmes, J.A.; Shiomitsu, S.K.; Soto, P.L.; McCurdy, C.R.; McMahon, L.R.; Wilkerson, J.L.; and Hiranita, T. (2022). Interactive Effects of μ-Opioid and Adrenergic-α2 Receptor Agonists in Rats: Pharmacological Investigation of the Primary Kratom Alkaloid Mitragynine and Its Metabolite 7-Hydroxymitragynine. J Pharmacol Exp Ther JPET-AR-2022-001192. Advance online publication. https://doi.org/10.1124/jpet.122.001192 PMID: 36153006 - 35. Ortiz, Y.T.; McMahon, L.R.; and Wilkerson, J.L. (2022). Medicinal Cannabis and Central Nervous System Disorders. Frontiers in Pharmacology, 13, 881810. https://doi.org/10.3389/fphar.2022.881810 PMID: 35529444
- 34. Zainul, Z.; Ma, B.; Koka, M.; Wilkerson, J.L.; Ortiz, Y.T.; Kerosuo, L.; and Chandran, V. (2022) Novel roles of phentolamine in protecting axon myelination, muscle atrophy, and functional recovery following nerve injury. Scientific Reports, 12(1), 3344. PMID: 35228612
- 33. Wilkerson, J.L.; Alberti, L.B.; Thakur, G.A.; Makriyannis, A; and Milligan, E.D. (2022) Peripherally administered cannabinoid receptor 2 (CB2R) agonists lose anti-allodynic effects in TRPV1 cation channel knockout mice, while intrathecal CB2R agonists remain efficacious and reduce TRPV1 expression in the dorsal spinal cord and DRG from a rodent model of sciatic neuropathy. Brain Res Jan 1;1774:147721. doi: 10.1016/j.brainres.2021.147721. Epub 2021 Nov 10. PMID: 34774500
- 32. Bilbrey, J.A.; Felix, J. S.; McMahon, L.R.; and Wilkerson, J.L. (2021) Evaluation of the terpenes β-caryophyllene, α-terpineol, and γ-terpinene in the mouse chronic constriction injury model of neuropathic pain: possible cannabinoid receptor involvement. Psychopharm: Advance online publication. PMID: 34846548
- 31. Wilkerson, J.L.; Bilbrey, J.A.; Felix, J.S.; Makriyannis, A.; and McMahon, L.R.
(2021). Untapped endocannabinoid pharmacological targets: Pipe dream or pipeline? Pharmacol Biochem Behav, 206: 73192. PMID: 33932409 - 30. Wilkerson, J.L.; Felix, J.S.; Bilbrey, J.A.; McCurdy, C.R.; and McMahon, L.R. (2021). Characterization of a mouse neuropathic pain model caused by the highly active antiviral therapy (HAART) Stavudine. Pharmacological Reports, 73(5):1457-1464. PMID: 33860918
- 29. Blanton, H.L.; Barnes, R.C.; McHann, M.C.; Bilbrey, J.A.; Wilkerson, J.L.; and
Guindon, J. (2021) Sex differences and the endocannabinoid system in pain. Pharmacol Biochem Behav 202:173107. PMID: 33444598 - 28. Obeng, S†.; Wilkerson, J.L†.; Leon, F.; Reeves, M.E.; Restrepo, L.F.; Gamez-Jimenez, L.R.; Patel, A.; Pennington, A.E.; Taylor, V.A.; Ho, N.P.; Braun, T.; Fortner, J.D.; Crowley, M.L.; Williamson, M.R.; Pallares, V.L.; Mottinelli, M.; Lopera-Londono, C.; McCurdy, C.R.; McMahon, L.R.; and Hiranita, T. (2021). Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for Mu-Opioid Receptor and Opioid-Like Behavioral Effects in Rats. J Pharmacol Exp Ther. 376(3), 410–427. PMID: 33384303
- 27. Wilkerson, J.L.; Alberti, L.B.; Kerwin, A.A.; Ledent, C.A.; Thakur, G.A.; Makriyannis, A; and Milligan, E.D. (2020) Peripheral versus central mechanisms of the cannabinoid type 2 receptor agonist AM1710 in a mouse model of neuropathic pain. Brain Behav 10:e01850. PMID: 32977358
- 26. Corrie, L.W.; Stokes, C.; Wilkerson, J. L.; Carroll, F.I.; McMahon, L.R.; and Papke, R.L. (2020). Nicotinic Acetylcholine Receptor Accessory Subunits Determine the Activity Profile of Epibatidine Derivatives. Mol Pharm, MOLPHARM-AR-2020-000037. Advance online publication. https://doi.org/10.1124/molpharm.120.000037 PMID: 32690626
- 25. Wilkerson, J.L.; Jiang, J; Felix, J.S.; Bray J.K.; da Silva, L.; Gharaibeh, R.Z.;
McMahon, L.R.; and Schmittgen, T.D. (2020) Alterations in mouse spinal cord and sciatic nerve microRNAs after the chronic constriction injury (CCI) model of neuropathic pain. Neurosci Letters 731, 135029. PMID: 32380144 - 24. Wilkerson, J.L.; Deba, F.; Crowley, M.L.; Hamouda, A.K.; and McMahon, L.R.
(2020) Advances in the In vitro and In vivo pharmacology of Alpha4beta2 nicotinic receptor positive allosteric modulators. [published online ahead of print, 2020 Feb 12]. Neuropharm. 168:108008. PMID: 32113032 - 23. Moerke, M.J.; McMahon, L.R.; and Wilkerson, J.L. (2020) More than smoke and patches:
the quest for pharmacotherapies to treat tobacco use disorder.
Pharmacological Reviews 72(2):527-557. PMID: 32205338 - 22. de Moura, F.B.; Wilkerson, J.L.; McMahon, L.R. (2020) Unexpected loss of
sensitivity to the nicotinic acetylcholine receptor antagonist activity of mecamylamine and dihydro-beta-erythroidine in nicotine-tolerant mice. Brain Behav:e01581. PMID: 32092237 - 21. Grenning, A.J.; Navaratne, P.V.; Wilkerson, J.L.; Ranasinghe, K.D.; Semenova, E.; Felix, J.S.; Ghiviriga, I.; Roitberg, A. and McMahon, L.R. (2020) Axially-Chiral Cannabinols: A New Platform for Cannabinoid-Inspired Drug Discovery. ChemMedChem. PMID: 32061146
- 20. Wilkerson, J.L.; Felix, J.S., Restrepo, L.F.; Ansari, M.I.; Coop A.; and McMahon L.R. (2019) The Effects of Morphine, Baclofen, and Buspirone Alone and in Combination on Schedule-Controlled Responding and Hot Plate Antinociception in Rats. J Pharmacol Exp Ther. 370: 380-389. PMID: 31235534.
- 19. Hiranita, T.; Leon, F.; Felix, J.S.; Restrepo, L.F.; Reeves, M.E.; Pennington, A.E.; Obeng, S.; Avery, B.A.; McCurdy, C.R.; McMahon, L.R.; and Wilkerson, J.L. (2019) The effects of mitragynine and morphine on schedule-controlled responding and antinociception in rats. Psychopharmacology (Berl). 236: 2725-2734. PMID: 31098655
- 18. Wilkerson, J.L; Schulze, D.R.; and McMahon, L.R. (2019) Tolerance and
dependence to Delta9-tetrahydrocannabinol in rhesus monkeys: Activity assessments. PLoS One. 14(3):e0209947. PMID: 30861005 - 17. Sim-Selley, L.J.; Wilkerson, J.L.; Lazenka, M.F.; Welch, S.P.; Lichtman, A.H.; and Selley, D.E. (2018) Differential Tolerance to Acute and Chronic FTY720-Mediated Antinociception: Role of S1P Receptor Adaptation. J Pharmacol Exp Ther. 366(3):509-18. PMID: 29945931
- 16. Curry, Z., Wilkerson, J.L.; Bagdas, D.; Kyte, S.; Patel, N.; Donvito, G.; Mustafa,
M.A.; Poklis, J.; Niphakis, M.; Hsu K.L.; Cravatt, B.F.; Gewirtz, D.A.; Damaj, M.I.; and Lichtman, A.H. (2018) Monoacylglycerol lipase inhibitors reverse paclitaxel-induced nociceptive behavior and proinflammatory markers in a mouse model of chemotherapy induced peripheral neuropathy. J Pharmacol Exp Ther 366(1):169-83. PMID: 29540562 - 15. Wilkerson, J.L.; Curry, Z.A.; Kinlow, P.; Hsu, K.L.; van der Stelt, M.; Cravatt, B.F.; and Lichtman, A.H. (2018) Characterization of the marble burying assay as an effective measure of pain depressed behavior in mice. Pain 159(6):1155-65. PMID: 29528965
- 14. Donvito, G.; Nass, S.; Wilkerson, J.L.; Curry, Z.A.; Schurman, L.D.; Kinsey, S.; and Lichtman, A.H. (2018). The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain. Neuropsychopharm. PMID: 28857069
- 13. Wilkerson, J.L.; Donvito, G.; Grim, T.W.; Mason, B.L.; Morales, A.; Abdullah, R.A.; Ogasawara, D.; Cravatt, B.F.; and Lichtman, A.H. (2017). Investigation of Diacylglycerol Lipase Alpha Inhibition in the LPS Model of Inflammatory Pain in Mice. J Pharmacol Exp Ther. 363(3) 394-401. PMID: 28970359
- 12. Wilkerson, J.L.; Ghosh, S.; Mustafa, M.A.; Abdullah, R.A.; Cabrera, R; Maldonado, R.L.; Cravatt, B.F.; and Lichtman, A.H. (2017) The Endocannabinoid Hydrolysis Inhibitor SA-57 Augments the Antinociceptive Effects of Morphine and Reduces Heroin Seeking Behavior in Mice. Neuropharm 114:156-167. PMID: 27890602
- 11. Donvito, G.; Wilkerson, J.L.; Damaj, M.I.; and Lichtman, A.H. (2016)
Palmitoylethanolamide reverses paclitaxel-induced allodynia in mice. J Pharmacol Exp Ther 359(2):310-318. PMID: 27608657 - 10. Bagdas, D.†; Wilkerson, J.L.†; Kulkarni, A.; Toma, W.; Alsharari, S.; Gul, Z.;
Lichtman, A.; Papke, R.; Thakur, G.; and Damaj, M.I. (2016) The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain. Br J Pharmacol 173(16):2506-2520. PMID: 27243753 - 9. Wilkerson, J.L.; Ghosh, S.; Bagdas, D.; Mason, B.L.; Crowe, M.S.; Hsu, K.L.; Wise, L.E.; Kinsey, S.G.; Damaj, M.I.; Cravatt, B.F.; and Lichtman, A.H. (2016) Diacylglycerol lipase beta inhibition reverses nociceptive behavior in mouse models of inflammatory and neuropathic pain. Br J Pharmacol 173(10):1678-1692. PMID: 26915789
- 8. Wilkerson, J.L.; Niphakis, M.J.; Grim, T.W.; Mustafa, M.A.; Abdullah, R.A.; Dewey, W.L.; Akbarali, H.; Banks, M.L.; Wise, L.E.; Cravatt, B.F.; and Lichtman, A.H. (2016) Monoacylglycerol lipase inhibition produces opioid sparing effects in a mouse model of neuropathic pain. J Pharmacol Exp Ther 357(1):145-56. PMID: 26791602
- 7. Mukhopadhyay, P.; Baggelaar, M.; Erdelyi, K.; Cao, Z.; Cinar, R.; Fezza, F.;
Ignatowska-Janlowska, B; Wilkerson, J.; van Gils, N.; Hansen, T.; Ruben, M.;
Soethoudt, M.; Heitman, L.; Kunos, G.; Maccarrone, M.; Lichtman, A.; Pacher, P.; van der Stelt, M. (2016) The novel, orally available and peripherally restricted selective cannabinoid CB2-receptor partial agonist LEI-101 prevents cisplatin-induced nephrotoxicity. Br J Pharmacol 173(3):446-58. PMID: 26398481 - 6. Ignatowska-Jankowska, B.†; Wilkerson, J.L.†, Mustafa M.; Abdullah R.; Niphakis M.; Wiley J.L.; Cravatt, B.F.; and Lichtman, A.H. (2015) Selective monoacylglycerol lipase inhibitors: Antinociceptive vs. cannabimimetic effects in mice. J Pharmacol Exp Ther 353:424-432. PMID:25762694
- 5. Dengler, E.C.; Alberti, L.B.; Bowman, B.N.; Kerwin, A.A.; Wilkerson, J.L; Moezzi D.R.; Limanovich E.; Wallace, J.A.; Milligan, E.D. (2014) Improvement of spinal non-viral IL-10 gene delivery by D-mannose as a transgene adjuvant to control chronic neuropathic pain. Journal of Neuroinflammation 11:92 1-21. PMID: 24884664
- 4. Dengler, E.C.; Kerwin, A.A.; Liu, J.; Torres, S., Olcott C.M.; Bowman, B.N.; Armijo, L.M.; Gentry, K.R.; Wilkerson, J.; Wallace, J.A.; Jiang, X.; Carnes, E.C.; Brinker C.J.; Milligan, E.D. (2013) Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord. Journal of Controlled Release 168: 209-224. PMID: 23517784
- 3. Wilkerson, J.L.; Gentry, K.R.; Dengler, E.C.; Wallace, J.A.; Kerwin, A.A.; Kuhn, M.N.; Alberti, L.B.; Armijo, L.M.; Thakur, G.A.; Makriyannis, A.; Milligan, E.D. (2012) Intrathecal cannabilactone CB2R agonist, AM1710, controls pathological pain and restores basal cytokines. Pain 153: 1091-1106. PMID: 22425445
- 2. Wilkerson, J.L.; Gentry, K.R.; Dengler, E.C.; Wallace, J.A.; Kerwin, A.A.; Alberti, L.B.; Thakur, G.A.; Makriyannis, A.; Milligan, E.D. (2012) Immunofluorescent spectral analysis reveals the intrathecal cannabinoid agonist, AM1241, produces spinal anti-inflammatory cytokine responses in neuropathic rats exhibiting relief from allodynia. Brain and Behavior 2: 155–177. PMID: 22574283
- 1. Wilkerson, J.L.; Milligan, E.D. (2011) The Central Role of Glia in Pathological Pain and the Potential of Targeting the Cannabinoid 2 Receptor for Pain Relief. ISRN Anesthesiology 2011: 1-19. PMID: 22442754
updated: 1/23/2023