Edmund Au, Ph.D.
The Au lab studies cortical interneurons, a diverse population of locally-projecting GABAergic cells. They are involved in regulating spike timing, signal refinement and cortical oscillations, all of which are critical to normal brain function. We are primarily focused on how cortical interneurons wire into cortical circuitry developmentally, and how their developmental dysfunction leads to neuropsychiatric illness.
Our general approach is a combination of mouse genetics, stem cell directed differentiation and in vitro assays. In order to study these cells in their native environment, we often transplant stem cell-derived interneurons in utero and study their integration into host cortex. Since stem cells start off as a blank slate, we have the opportunity to manipulate various stages of interneuron differentiation and maturation by manipulating the cells in vitro. In this manner, we can therefore delve into molecular mechanisms that govern the process of microcircuit assembly. We have also developed novel methods to study cortical interneuron synapse formation and function, which we are eager to apply to human disease modeling.
Dysfunction in cortical interneurons has been linked to a number of diseases including autism spectrum disorder, schizophrenia, epilepsy and attention deficit and hyperactivity disorder. We are interested in employing stem cell-based approaches to model neuropsychiatric disorders in order to study underlying disease mechanisms. From these studies we hope to pave the way towards more directed, specific and effective treatments for psychiatric ailments.
Whitehall Foundation Grant 2017
Irving Institute CaMPR BASIC Grant 2017
Irma T. Hirschl Foundation Award 2019
Genestine, M., Ambriz, D., Crabtree, G.W., Dummer, P., Molotkova, A., Quintero, M., Mela, A., Biswas, S., Feng, H., Zhang, C., et al. (2021). Vascular-derived SPARC and SerpinE1 regulate interneuron tangential migration and accelerate functional maturation of human stem cell-derived interneurons. Elife 10.
McKenzie MG, Cobbs LV, Dummer PD, Petros TJ, Halford MM, Stacker SA, Zou Y, Fishell GJ, Au E. (2019) Non-Canonical Wnt-Signaling through Ryk Regulates the Generation of Somatostatin- and Parvalbumin-Expressing Cortical Interneurons. Neuron. 103(5): 853-64.
Karayannis* T, Au E*, Patel J., Kruglikov I., Markx S., Delorme R., Heron D, Glessner J., Restituito S., Gordon A., Roy N.C., Gogos J., Rudy B., Rice M.E., Karyiorgou M., Hakonarson H., Bourgeron T., Hoeffer C., Tsien R.W., Peles E., Fishell G. (2014) Cntnap4 differentially contributes to GABAergic and Dopaminergic Synaptic Transmission. Nature. 511(7508): 236-40.
Au E., Ahmed T, Karayannis T., Biswas S., Gan L., Fishell G. (2013) A modular gain-offunction approach to generate cortical interneuron subtypes from ES cells. Neuron. 80(5): 1145-58.
Au E., Fishell G. (2008) Cortex shatters glass ceiling. Cell Stem Cell 3(5): 472-4.
Au E., Richter M.W., Vincent A.J., Tetzlaff W., Aebersold R., Sage E.H., Roskams A.J. (2007) SPARC from olfactory ensheathing cells stimulates Schwann cells to promote neurite outgrowth and enhances spinal cord repair. The Journal of Neuroscience. 27(27): 7208-21.
Au E, Fishell, G. (2006) Adult cortical neurogenesis: nuanced, negligible or nonexistent? Nature Neuroscience. 9: 1086-1088.
For a complete list of publications, please visit PubMed.gov
- Cell Lineage Specification
- Neuronal Migration
- Synaptic Specificity