Lab Members
Research Interests: Glutamate receptors mediate the vast majority of excitatory synaptic transmission in the brain. A major research effort in my lab is focused on regulation of glutamate receptor-mediated synaptic transmission in the brain by the co-activation of selected G-protein coupled receptors. A second research emphasis involves the use of microarray and associated technologies to identify novel targets and pathways involved in the basic cellular and molecular mechanisms of epilepsy. These research interests converge and have highlighted a role for cyclooxygenase-2 (COX2) signaling pathways in the cognitive deficits, impaired synaptic inhibition, and neurodegeneration caused by seizures. We are currently seeking the prostaglandin receptors responsible for each of these effects; we will then employ a chemical biology approach to develop novel small molecule modulators of these receptors in an effort to interrupt the development of epilepsy. As a whole our work integrates information from a variety of experimental strategies to contribute to a better understanding of epilepsy, with broad implications for other brain disorders including stroke and schizophrenia.
Asheebo Rojas, PhDResearch Interests: My research focuses on the understanding of the function of kainate receptors (KARs), with a particular emphasis on investigating the role of these receptors in the heightened hyper excitability of hippocampal neurons following pilocarpine induced status epilepticus (SE). The objectives of my project are: 1) to understand the role of prostanoid receptors in the protection of hippocampus neurodegeneration and inflammation following SE as recently it has been suggested that release of endogenous PGE2 in the hippocampus regulates membrane excitability, synaptic transmission, and plasticity; 2) to elucidate whether there is cross-talk between prostanoid receptors and kainate receptors that may allow for a heightened hyper excitability of hippocampal neurons; and 3) to understand the underlying molecular mechanisms involved. My experiments are directly relevant to the generation of epilepsy (epileptogenesis) and the neuropathologies associated with seizures. I use electrophysiological recordings of whole cell currents of recombinant receptors in heterologous expression systems along with immunohistochemical and pharmacological approaches to elucidate the molecular basis of receptor regulation. Immunohistochemistry revealed expression of prostanoid receptors and KARs in the CA3 region of the hippocampus. By expressing recombinant KARs and prostanoid receptors in the Xenopus oocyte heterologous expression system I found that activation of EP1 by PGE2 significantly potentiates heteromeric, but not homomeric KAR currents in a time- and dose-dependent manner. I have started to investigate the importance of a second messenger signaling cascade involving phospholipase C, Ca2+, and PKC in this receptor cross-talk. A better understanding of kainate and prostanoid receptor interactions may help to provide molecular and pharmacological targets for combating neuopathlogies associated with SE.
Nicholas Varvel, PhDResearch Interests: The innate immune response in the brain after status epilepticus.
Ms. Wang's research focuses on understanding the neurodegeneration and inflammation in the Status Epilepticus mice model after Epilepsy treatment. She performs all laboratory surgeries related to the Epilepsy model and Long-term EEG Monitoring in mice. Ms. Wang also manages the lab, trains students, takes care of protocols, and performs EP2 antagonists screening.
Di Chen is a Chinese visiting medical student through the Emory University School of Medicine where she will be for two years. She is currently working and studying in Dr. Dingledine's research lab. Her research focuses on the EP2 receptors on human circulation monocytes.