Edward Perez-Reyes


Primary Appointment

Professor, Pharmacology


  • 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

Current work in the lab is focused on developing gene therapies for pharmacoresistant epilepsies and insulin replacement. In these projects we are leveraging our experience in molecular cloning to develop novel adeno-associated viral (AAV) targeting vectors capable of delivering genes of interest. In a project funded by a CURE Challenge Award, we validated the ability of a modified K+ leak channel to reduce status epilepticus (Epilepsia, PMID: 24299204). Current funding focuses on developing novel drug-inducible genetic switches to control therapeutic gene delivery. Our work on insulin replacement is supported by donations from the Manning Foundation to the School of Medicineâs grant program âLaunchpad for Diabetes.â This project is a collaboration with Thurl Harris, also in the Pharmacology department. Our work on epilepsy includes both developing novel models of temporal lobe epilepsy (TLE; Epilepsia, PMID: 32954490), exploring the causes of epilepsy, and developing therapies to prevent TLE seizures (DOI 10.3390/ijms241411347). Our epilepsy work is a collaboration with Drs. Ukpong Eyo (Neuroscience), Mark Beenhakker (Pharmacology), Manoj Patel (Anesthesiology), Harald Sontheimer (Neuroscience) and Jaideep Kapur (Neurology). We have also leveraged our molecular cloning experience to advance studies in hearing with Dr. Jung-Bum Shin (Neuroscience) and in the control of breathing with Drs. Yingtang Shi and Doug Bayliss (Pharmacology). Our latest tools for neuroscience are optimized Cre-dependent AAVs with minimal off-target expression. For a complete list of scientific contributions see my profile on Google Scholar: perez-reyes e .

Personal Statement

During my doctoral training in Neuropharmacology I was mentored by Drs. Tom Dunwiddie and Dermot Cooper, where I studied inhibition of firing in hippocampal slices and explored the regulation of Ca/CaM-activated adenylyl cyclase. During my postdoctoral training I was mentored by Drs. Lutz Birnbaumer and Arthur âBuzzâ Brown, where I studied the molecular biology and electrophysiology of high voltage-activated calcium channels. During my independent career, my highest impact work was cloning the low voltage-activated T-type calcium channel family. In 2009, I began to transform my research, moving beyond T-type Ca2+ channels and their roles in absence epilepsy, and moving towards translational studies to develop cures for epilepsy. My >25 years of molecular biology experience provided me with the tools and background to develop novel AAV targeting vectors. Indeed, many of my recent publications resulted from collaborative projects where I contributed novel viral vectors to deliver genes or knock-down expression in specific neurons.
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.


  • Predoctoral Training in Neuroscience
  • Training in Cell and Molecular Biology
  • Training in the Pharmacological Sciences

Selected Publications


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


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


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


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


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


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


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


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


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


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


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


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


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


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