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.
Research Interests: I provide medicinal chemistry support to a variety of projects involving small molecules from proof of concept to clinical trials, but currently focus on developing highly selective EP2 antagonists by iterative chemical design, synthesis and biotesting. I often use X-ray and homology models, and then structure property calculations in design and optimization of drug like properties in the chemical classes. Inflammation is a key component in a variety of CNS diseases including status epilepticus, epilepsy, amyotrophic lateral sclerosis and Alzheimer’s disease; peripheral diseases such as arthritis and cancer. The overarching goal of my research is to find a clinically useful EP2 modulator to use as an anti-inflammatory agent on patients with chronic inflammatory disease, where EP2 is shown to play a deleterious role (Ganesh J. Med. Chem. 2014). I am open to collaborate and work with new investigators within and outside of Emory University, with an overall goal of deriving a medicinal chemistry solution to a biological problem. I have acquired medicinal chemistry knowledge from the laboratories of Prof. Dr. David Kingston at Virginia Tech, and Dr. Dennis Liotta at Emory Institute for Drug Development (see. Ganesh et al., PNAS 2004, Ganesh et al., J. Med. Chem. 2007, Ganesh, T. Bioorg. Med. Chem. 2007). I have worked on a variety of medicinal chemistry projects and became proficient in conducting bioassays, interpreting the biological results relevant to drug discovery. I have interacted with multidisciplinary teams (Biochemists, biology, bioinformatics, drug metabolism and pharmacokinetic teams) to design and interpret experiments and to coordinate the results for publications and presentations. I joined the Department of Pharmacology in 2010 as an Assistant Professor, with space and equipment provided by Dr. Ray Dingledine (Professor and Chair of Pharmacology). Moreover, I have demonstrated my scientific accomplishments with approximately 50 peer-reviewed publications, patents and presentations.
Research 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.
MD Shabber, PhD
Dr. Shabber's research is primarily focused on medicinal chemistry around EP2 selective inhibitors for use in the treatment of neurodegenerative diseases.
Dr. Amaradhi's research focuses on the development of selective EP2 antagonists towards the biological problems. Her long term goals include development of methodologies using organo catalysts and their application in the synthesis of biologically active molecules and asymmetric catalysis.
Amy (Wenyi) Wang
Research Specialist, Lead email@example.com
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.
Visiting International Medical Student
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.