Edward Perez-Reyes

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, Molecular Pharmacology, 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 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. Our epilepsy work is a collaboration with Drs. Ukpong Eyo (Neuroscience), 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). 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.

Training

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

Selected Publications

Shi Yingtang, Stornetta Daniel S, Reklow Robert J, Sahu Alisha, Wabara Yvonne, Nguyen Ashley, Li Keyong, Zhang Yong, Perez-Reyes Edward, Ross Rachel A, A brainstem peptide system activated at birth protects postnatal breathing, 2020; Nature. (589) 426-430. PMID: | PMCID: PMC7855323

Straub Justyna, Gawda Agnieszka, Ravichandran Pranav, McGrew Bailey, Nylund Elsa, Kang Julianna, Burke Cassidy, Vitko Iuliia, Scott Michael, Williamson John, Joshi Suchitra, Kapur Jaideep, Perez-Reyes Edward, Characterization of kindled VGATâCre mice as a new animal model of temporal lobe epilepsy, 2020; Epilepsia. 61(10) 2277-2288. PMID: | PMCID: 32954490

Nigam Aradhya, Hargus Nicholas J., Barker Bryan S., Ottolini Matteo, Hounshell James A., Bertram Edward H., Perez-Reyes Edward, Patel Manoj K., Inhibition of T-Type calcium channels in mEC layer II stellate neurons reduces neuronal hyperexcitability associated with epilepsy, 2019; Epilepsy Research. 154(154) 132-138. PMID: | PMCID: PMC6643284

Joshi S., Sun H., Rajasekaran K., Williamson J., Perez-Reyes E., Kapur J., A novel therapeutic approach for treatment of catamenial epilepsy, 2017; Neurobiol Dis. (111) 127-137. PMID: | PMCID: PMC5803337

Eckle VS, Shcheglovitov A, Vitko I, Dey D, Yap CC, Winckler B, Perez-Reyes E, Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure susceptibility., 2013; The Journal of physiology. 592(0) 795-809. PMID: 24277868 | PMCID: PMC3934715

Dey D, Eckle VS, Vitko I, Sullivan KA, Lasiecka ZM, Winckler B, Stornetta RL, Williamson JM, Kapur J, Perez-Reyes E, A potassium leak channel silences hyperactive neurons and ameliorates status epilepticus., 2013; Epilepsia. 55(2) 203-13. PMID: 24299204 | PMCID: PMC4161023

Vitko I, Chen Y, Arias JM, Shen Y, Wu XR, Perez-Reyes E, Functional characterization and neuronal modeling of the effects of childhood absence epilepsy variants of CACNA1H, a T-type calcium channel., 2005; The Journal of neuroscience : the official journal of the Society for Neuroscience. 25(19) 4844-55. PMID: 15888660

Du Ting-Ting, Dewey James B., Wagner Elizabeth L., Cui Runjia, Heo Jinho, Park Jeong-Jin, Francis Shimon P., Perez-Reyes Edward, Guillot Stacey J., Sherman Nicholas E., Xu Wenhao, Oghalai John S., Kachar Bechara, Shin Jung-Bum, LMO7 deficiency reveals the significance of the cuticular plate for hearing function, ; Nature Communications. 10(1) 1117. PMID:

Cottrell G. S., Soubrane C. H., Hounshell J. A., Lin H., Owenson V., Rigby M., Cox P. J., Barker B. S., Ottolini M., Ince S., Bauer C. C., Perez-Reyes E., Patel M. K., Stevens E. B., Stephens G. J., CACHD1 is an alpha2delta-like protein that modulates CaV3 voltage-gated calcium channel activity, ; J Neurosci. 38(43) 9186-9201. PMID:

Shi Y., Abe C., Holloway B. B., Shu S., Kumar N. N., Weaver J. L., Sen J., Perez-Reyes E., Stornetta R. L., Guyenet P. G., Bayliss D. A., Nalcn Is a "leak" sodium channel that regulates excitability of brainstem chemosensory neurons and breathing, ; J Neurosci. 36(31) 8174-87. PMID:

Park J., Yu Y. P., Zhou C. Y., Li K. W., Wang D., Chang E., Kim D. S., Vo B., Zhang X., Gong N., Sharp K., Steward O., Vitko I., Perez-Reyes E., Eroglu C., Barres B., Zaucke F., Feng G., Luo Z. D., Central Mechanisms Mediating Thrombospondin-4-induced Pain States, ; J Biol Chem. 291(25) 13335-48. PMID: