Edward Perez-Reyes
- Email: eperez@virginia.edu
- Phone: 434-982-4440
- Fax: 434-982-3878
- Website: https://med.virginia.edu/perez-reyes-lab/
Primary Appointment
Professor, Pharmacology
Education
- BA, Chemistry, University of North Carolina
- PhD, Pharmacology, University of Colorado, Denver
- Research Fellowship, Electrophysiology, Stanford University
Research Disciplines
Biophysics, Biotechnology, Metabolism, Molecular Biology, Molecular Pharmacology, Neuroimmunology, Neuroscience, Translational Science
Research Interests
Exploring epilepsy circuits then preventing seizures using gene therapies. Developing drug-inducible genetic switches for insulin replacement gene therapies.
Research Description
Personal Statement
Over these last 5 years my lab has been focused on engineering and testing drug-inducible gene therapy vectors (activated by doxycycline, Dox-On). Focal epilepsies such as mesial temporal lobe epilepsy (TLE) are devastating disorders that are largely pharmacoresistant and often treated by surgical resection, therefore more likely to be treated with gene therapy. In collaboration with Dr. Jaideep Kapur, we were awarded a CURE Challenge Award to test a target-independent approach for seizure control -- overexpression of K+ leak channel. We are now realizing the fruits of this labor, publishing a paper in Epilepsia on treatment of status epilepticus and NIH funding to extend this approach to chronic TLE. I have enjoyed immersing myself in the field of epilepsy, where I have ârolled up my sleevesâ and learned how to generate new models of TLE, record seizures using long-term 24/7 video/EEG, inject AAVs into specific brain regions, and develop techniques to validate the neurons infected as well as the circuits they control. The University of Virginia has pioneered the development of animal models of TLE. Therefore, I realized the potential provided by our chance discovery that kindling rapidly induces spontaneous seizures in VGAT-Cre mice. We are improving the model for drug screening and using the model to explore the mechanisms of epileptogenesis.
Training
- Predoctoral Training in Neuroscience
- Training in Cell and Molecular Biology
- Training in the Pharmacological Sciences
Selected Publications
2023
Alexander, S. P. H., Mathie, A. A., Peters, J. A., Veale, E. L., Striessnig, J., Kelly, E., . . . Zhu, M. (2023). The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. BRITISH JOURNAL OF PHARMACOLOGY, 180, S145-S222. doi:10.1111/bph.16178
Burke, C. T., Vitko, I., Straub, J., Nylund, E. O., Gawda, A., Blair, K., . . . Perez-Reyes, E. (2023). EpiPro, a Novel, Synthetic, Activity-Regulated Promoter That Targets Hyperactive Neurons in Epilepsy for Gene Therapy Applications. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(19). doi:10.3390/ijms241914467
Sullivan, K. A. A., Vitko, I., Blair, K., Gaykema, R. P. P., Failor, M. J. J., San Pietro, J. M. M., . . . Perez-Reyes, E. (2023). Drug-Inducible Gene Therapy Effectively Reduces Spontaneous Seizures in Kindled Rats but Creates Off-Target Side Effects in Inhibitory Neurons. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(14). doi:10.3390/ijms241411347
Gibbs-Shelton, S., Benderoth, J., Gaykema, R. P., Straub, J., Okojie, K. A., Uweru, J. O., . . . Eyo, U. B. (2023). Microglia play beneficial roles in multiple experimental seizure models. GLIA, 71(7), 1699-1714. doi:10.1002/glia.24364
2022
Upchurch, C. M., Yeudall, S., Pavelec, C. M., Manjegowda, M., Bochkis, I. M., Scott, M., . . . Leitinger, N. (2022). Virus-induced Hepatic Expression of an Oxidized Phospholipid-binding Antibody Fragment Prevents Initiation of Hepatic Steatosis and Progression to Fibrosis.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36 Suppl 1. doi:10.1096/fasebj.2022.36.s1.l8081
Upchurch, C. M., Yeudall, S., Pavelec, C. M., Merk, D., Greulich, J., Manjegowda, M., . . . Leitinger, N. (2022). Targeting oxidized phospholipids by AAV-based gene therapy in mice with established hepatic steatosis prevents progression to fibrosis. SCIENCE ADVANCES, 8(28). doi:10.1126/sciadv.abn0050
Salvati, K. A., Ritger, M. L., Davoudian, P. A., O'Dell, F., Wyskiel, D. R., Souza, G. M. P. R., . . . Beenhakker, M. P. (2022). AMPK-mediated potentiation of GABAergic signalling drives hypoglycaemia-provoked spike-wave seizures. BRAIN, 145(7), 2332-2346. doi:10.1093/brain/awac037
2021
Alexander, S. P. H., Mathie, A., Peters, J. A., Veale, E. L., Striessnig, J., Kelly, E., . . . Zhu, M. (2021). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Ion channels. BRITISH JOURNAL OF PHARMACOLOGY, 178, S157-S245. doi:10.1111/bph.15539
Straub, J., Vitko, I., Gaykema, R. P., & Perez-Reyes, E. (2021). Preparation and Implantation of Electrodes for Electrically Kindling VGAT-Cre Mice to Generate a Model for Temporal Lobe Epilepsy. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (174). doi:10.3791/62929
Correia Rocha, I. R., Perez-Reyes, E., & Chacur, M. (2021). Effect of photobiomodulation on mitochondrial dynamics in peripheral nervous system in streptozotocin-induced type 1 diabetes in rats. PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, 20(2), 293-301. doi:10.1007/s43630-021-00018-w
2020
Shi, Y., Stornetta, D. S., Reklow, R. J., Sahu, A., Wabara, Y., Nguyen, A., . . . Bayliss, D. A. (2021). A brainstem peptide system activated at birth protects postnatal breathing. NATURE, 589(7842), 426-+. doi:10.1038/s41586-020-2991-4
Straub, J., Gawda, A., Ravichandran, P., McGrew, B., Nylund, E., Kang, J., . . . Perez-Reyes, E. (2020). Characterization of kindled VGAT-Cre mice as a new animal model of temporal lobe epilepsy. EPILEPSIA, 61(10), 2277-2288. doi:10.1111/epi.16651
2019
Catterall, W. A., Perez-Reyes, E., Snutch, T. P., & Striessnig, J. (n.d.). Voltage-gated calcium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide to Pharmacology CITE, 2019(4). doi:10.2218/gtopdb/f80/2019.4
Wulczyn, K., Perez-Reyes, E., Nussbaum, R. L., & Park, M. (2019). Primary aldosteronism associated with a germline variant in CACNA1H. BMJ CASE REPORTS, 12(5). doi:10.1136/bcr-2018-229031
Du, T. -T., Dewey, J. B., Wagner, E. L., Cui, R., Heo, J., Park, J. -J., . . . Shin, J. -B. (2019). LMO7 deficiency reveals the significance of the cuticular plate for hearing function. NATURE COMMUNICATIONS, 10. doi:10.1038/s41467-019-09074-4
Nigam, A., Hargus, N. J., Barker, B. S., Ottolini, M., Hounshell, J. A., Bertram, E. H. I. I. I., . . . Patel, M. K. (2019). Inhibition of T-Type calcium channels in mEC layer II stellate neurons reduces neuronal hyperexcitability associated with epilepsy. EPILEPSY RESEARCH, 154, 132-138. doi:10.1016/j.eplepsyres.2019.05.006
2018
Cottrell, G. S., Soubrane, C. H., Hounshell, J. A., Lin, H., Owenson, V., Rigby, M., . . . Stephens, G. J. (2018). CACHD1 is an α2δ-Like Protein That Modulates CaV3 Voltage-Gated Calcium Channel Activity. JOURNAL OF NEUROSCIENCE, 38(43), 9186-9201. doi:10.1523/JNEUROSCI.3572-15.2018
Joshi, S., Sun, H., Rajasekaran, K., Williamson, J., Perez-Reyes, E., & Kapur, J. (2018). A novel therapeutic approach for treatment of catamenial epilepsy. NEUROBIOLOGY OF DISEASE, 111, 127-137. doi:10.1016/j.nbd.2017.12.009
2017
Chemin, J., Taiakina, V., Monteil, A., Piazza, M., Guan, W., Stephens, R. F., . . . Spafford, J. D. (2017). Calmodulin regulates Cav3 T-type channels at their gating brake. JOURNAL OF BIOLOGICAL CHEMISTRY, 292(49), 20010-20031. doi:10.1074/jbc.M117.807925
Becker, F., Reid, C. A., Hallmann, K., Tae, H. -S., Phillips, A. M., Teodorescu, G., . . . Maljevic, S. (2017). Functional variants in HCN4 and CACNA1H may contribute to genetic generalized epilepsy.. Epilepsia open, 2(3), 334-342. doi:10.1002/epi4.12068
Lee, N., Jeong, S., Kim, K. -C., Kim, J. -A., Park, J. -Y., Kang, H. -W., . . . Lee, J. -H. (2017). Ca2+ Regulation of Cav3.3 T-type Ca2+ Channel Is Mediated by Calmodulin. MOLECULAR PHARMACOLOGY, 92(3), 347-357. doi:10.1124/mol.117.108530
2016
Park, J., Yu, Y. P., Zhou, C. -Y., Li, K. -W., Wang, D., Chang, E., . . . Luo, Z. D. (2016). Central Mechanisms Mediating Thrombospondin-4-induced Pain States. JOURNAL OF BIOLOGICAL CHEMISTRY, 291(25), 13335-13348. doi:10.1074/jbc.M116.723478
Shi, Y., Abe, C., Holloway, B. B., Shu, S., Kumar, N. N., Weaver, J. L., . . . Bayliss, D. A. (2016). Nalcn Is a "Leak" Sodium Channel That Regulates Excitability of Brainstem Chemosensory Neurons and Breathing. JOURNAL OF NEUROSCIENCE, 36(31), 8174-8187. doi:10.1523/JNEUROSCI.1096-16.2016
Warthen, D. M., Lambeth, P. S., Ottolini, M., Shi, Y., Barker, B. S., Gaykema, R. P., . . . Scott, M. M. (2016). Activation of Pyramidal Neurons in Mouse Medial Prefrontal Cortex Enhances Food-Seeking Behavior While Reducing Impulsivity in the Absence of an Effect on Food Intake. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 10. doi:10.3389/fnbeh.2016.00063
2015
Karmazinova, M., Jaskova, K., Griac, P., Perez-Reyes, E., & Lacinova, L. (2015). Contrasting the roles of the I-II loop gating brake in CaV3.1 and CaV3.3 calcium channels. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 467(12), 2519-2527. doi:10.1007/s00424-015-1728-y
Wang, G., Bochorishvili, G., Chen, Y., Salvati, K. A., Zhang, P., Dubel, S. J., . . . Zhu, J. J. (2015). CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy. GENES & DEVELOPMENT, 29(14), 1535-1551. doi:10.1101/gad.260869.115
Kumar, N. N., Velic, A., Soliz, J., Shi, Y., Li, K., Wang, S., . . . Bayliss, D. A. (2015). Regulation of breathing by CO2 requires the proton-activated receptor GPR4 in retrotrapezoid nucleus neurons. SCIENCE, 348(6240), 1255-1260. doi:10.1126/science.aaa0922
2014
Perez-Reyes, E., & Lee, J. -H. (2014). Ins and outs of T-channel structure function. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 466(4), 627-633. doi:10.1007/s00424-013-1419-5
Eckle, V. -S., Shcheglovitov, A., Vitko, I., Dey, D., Yap, C. C., Winckler, B., & Perez-Reyes, E. (2014). Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure susceptibility. JOURNAL OF PHYSIOLOGY-LONDON, 592(4), 795-809. doi:10.1113/jphysiol.2013.264176
Dey, D., Eckle, V. -S., Vitko, I., Sullivan, K. A., Lasiecka, Z. M., Winckler, B., . . . Perez-Reyes, E. (2014). A potassium leak channel silences hyperactive neurons and ameliorates status epilepticus. EPILEPSIA, 55(2), 203-213. doi:10.1111/epi.12472
2013
Seo, H., Li, H. Y., Perez-Reyes, E., & Lee, J. -H. (2013). Effects of Eugenol on T-type Ca2+ Channel Isoforms. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 347(2), 310-317. doi:10.1124/jpet.113.207936
2012
Shcheglovitov, A., Vitko, I., Lazarenko, R. M., Orestes, P., Todorovic, S. M., & Perez-Reyes, E. (2012). Molecular and biophysical basis of glutamate and trace metal modulation of voltage-gated Cav2.3 calcium channels. JOURNAL OF GENERAL PHYSIOLOGY, 139(3), 219-234. doi:10.1085/jgp.201110699
Hargus, N. J., Jennings, C., Perez-Reyes, E., Bertram, E. H., & Patel, M. K. (2012). Enhanced actions of adenosine in medial entorhinal cortex layer II stellate neurons in temporal lobe epilepsy are mediated via A1-receptor activation. EPILEPSIA, 53(1), 168-176. doi:10.1111/j.1528-1167.2011.03337.x
2011
Karmazinova, M., Baumgart, J. P., Perez-Reyes, E., & Lacinova, L. (2011). The voltage dependence of gating currents of the neuronal CAV3.3 channel is determined by the gating brake in the I-II loop. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 461(4), 461-468. doi:10.1007/s00424-011-0937-2
2010
Strege, P. R., Sha, L., Beyder, A., Bernard, C. E., Perez-Reyes, E., Evangelista, S., . . . Farrugia, G. (2010). T-type Ca2+ channel modulation by otilonium bromide. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 298(5), G706-G713. doi:10.1152/ajpgi.00437.2009
Kang, H. -W., Vitko, I., Lee, S. -S., Perez-Reyes, E., & Lee, J. -H. (2010). Structural Determinants of the High Affinity Extracellular Zinc Binding Site on Cav3.2 T-type Calcium Channels. JOURNAL OF BIOLOGICAL CHEMISTRY, 285(5), 3271-3281. doi:10.1074/jbc.M109.067660
Perez-Reyes, E. (2010). G Protein-Mediated Inhibition of Cav3.2 T-Type Channels Revisited. MOLECULAR PHARMACOLOGY, 77(2), 136-138. doi:10.1124/mol.109.062133
Perez-Reyes, E. (2010). Characterization of the gating brake in the I-II loop of CaV3 T-type calcium channels. CHANNELS, 4(6), 453-458. doi:10.4161/chan.4.6.12889