Molecular and cellular physiology of epilepsy-associated genes.
Our interest is to reveal the mechanisms by which epilepsy-associated molecules and signaling networks lead to epileptogenesis in the neonatal and infantile brain. In the current genomic era, gene mutations are identified in pediatric patients with increasing frequency, but it is unclear how the myriad of identified proteins and signaling networks are organized to regulate neuronal excitability. Our lab addresses this question using a multidisciplinary approach that combines electrophysiology, pharmacology and microscopy in genetically modified mice lines. Much of our work has dissected the cell-type and brain-region specific effects that epilepsy-associated potassium channel genes have on neuronal physiology. Such knowledge is critical for the development of new anticonvulsant molecules that have a more targeted action in the brain. Going forward, we will continue to study the role of epilepsy-associated genes, expanding our research into the mechanisms underlying the seizures triggered by recently identified mutations in non-ion channel genes.
We are now seeking motivated graduate students! Send inquires to firstname.lastname@example.org or apply directly to the PNB program.
Soh H, Park S, Ryan K, Springer K, Maheshwari A, Tzingounis AV. Deletion of KCNQ2/3 potassium channels from PV+ interneurons leads to homeostatic potentiation of excitatory transmission. Elife. 2018 Nov 1;7. pii: e38617.
Niday Z, Tzingounis AV. Potassium Channel Gain of Function in Epilepsy: An Unresolved Paradox. Neuroscientist. 2018 Aug;24(4):368-380. Epub 2018 Mar 15.
Abiraman K, Tzingounis AV, Lykotrafitis G.KCa2 channel localization and regulation in the axon initial segment. FASEB J. 2018 Jan 5:fj201700605R. doi: 10.1096/fj.201700605R
Tzingounis AV. SMITten for KCNQ Channels. Biophys J. 2017 Aug 8;133(3):503-505.
Zhang Y, Abiraman K, Li H, Pierce DM, Tzingounis AV, Lykotrafitis G. Modeling of the axon membrane skeleton structure and implications for its mechanical properties. PLoS Comput Biol. 2017 Feb 27; 13(2):e1005407.
Niday Z, Hawkins VE, Soh H, Mulkey DK, Tzingounis AV. Epilepsy-Associated KCNQ2 Channels Regulate Multiple Intrinsic Properties of Layer 2/3 Pyramidal Neurons. J Neurosci. 2017 Jan 18;37(3):576-586.
Abiraman K, Sah M, Walikonis RS, Lykotrafitis G, Tzingounis AV. Tonic PKA Activity Regulates SK Channel Nanoclustering and Somatodendritic Distribution. J Mol Biol. 2016 Jun 5;428(11):2521-37.