Professor of Pharmacology, UVa
Calcium entry via voltage-gated calcium channels is a key event in neuronal firing, muscle contraction, gene expression, and secretion of neurotransmitters and hormones. Importantly, voltage-gated calcium channels are the site of action of a number of clinically relevant drugs, termed "calcium channel blockers." Although these drugs are used to treat cardiovascular disorders like high blood pressure, the goal of our research is treat certain forms of pain and epilepsy with novel calcium channel blockers.
A major contribution of the Perez-Reyes laboratory has been on the molecular physiology and pharmacology of voltage-gated calcium channels, and in particular, the cloning of low voltage-activated T-type calcium channels. Their cloning opened many doors on their biophysics, localization, role in neuronal excitability, and pharmacology. This work combined a wide array of techniques such as molecular cloning, electrophysiological recordings of whole cell and single channel currents, and confocal microscopy. For review see: “Molecular physiology of low-voltage-activated T-type calcium channels” Physiol. Rev. 83:117-161, 2003, PMID: 12506128. Our T-channel studies continue to focus on how mutations in Cav3.2 alter its function leading to diseases such as epilepsy. Our most current study focused on the mechanisms by which Cav3.2 mutations found in childhood absence epilepsy patients lead to hyperexcitability ( J. Physiol.).
Current work in the lab is focused on developing gene therapies for neuropathic pain and focal epilepsies. Figure below shows drug-inducible delivery of two genes from a single adeno-associated virus in the brain (GFP and mCherry). In these projects we are leveraging our experience in molecular cloning to develop novel adeno-associated viral (AAV) targeting vectors capable of delivering either short-hairpinned RNAs (shRNAs) or genes of interest. For example, in a project funded by a CURE Challenge Award, we are testing the ability of a modified K+ leak channel to reduce seizures (published in Epilepsia). In a second project recently funded by NINDS, we are testing the ability of an shRNA directed against the sodium channel beta4 subunit to reduce seizures.
Both projects are made possible by collaborations with local epilepsy experts, including Jaideep Kapur, John Williamson, and Edward Bertram, as well as other faculty (and graduate students) UVa’s Neuroscience Graduate Program: Doug Bayliss, Patrice Guyenet, Michael Scott, Bettina Winkler, Manoj Patel (James Hounshell) and Mark Beenhakker (Peter Klein and Kathryn Salvati).
We find these new translational neuroscience projects very exciting and hope they will have a major impact on patient care.
Current lab members:
Iuliia Vitko, Instructor
Deborah L. Perez-Reyes (my hands)
Kyle Sullivan, Distinguished Neuroscience Undergraduate Major here @UVa; special shout out for winning the best poster prize at the Central Virginia Chapter of Society for Neuroscience, 2014 Symposium Undergraduate Student.
Shelby Shultz, UVa Undergraduate School of Arts and Sciences
Kathryn Brodie, UVa Undergraduate School of Arts and Sciences
Former lab members who left in the last few years:
Alex Shcheglovitov, former Post-doc, now at Stanford University and seeking his first faculty position.
Veit Simon-Eckle, former post-doc now at the University of Tubingen.
Joel Baumgart, former Ph.D. Student, now a post-doc at Weill Cornell Medical College.
Amol Bhandare, former Research Assistant, now in a Ph.D. program.
Conor Jennings, UVa Undergraduate Student, now in a M.S. program.
Ima Arias, former Visiting Ph.D. student from UNAM.
Everardo Hernandez-Plata, Visiting Ph.D. student from UNAM.
Deblina Dey, former Ph.D. student, now a post-doc at the University of California-Irvine.
For a complete list of scientific contributions see my profile on Google Scholar: perez-reyes e
updated April 25, 2014
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