- Jan and Dan Duncan Neurological Research Institute 1250 Moursund St. NRI, N.1270.02 Mail Stop: NRI 1250 Houston, Texas 77030 United States (832) 824-8109
- Jan and Dan Duncan Neurological Research Institute 1250 Moursund St. NRI, Suite 1250 Mail Stop: NRI 1250 Houston, Texas 77030 United States (832) 824-8946
- Assistant Professor
- Department of Neuroscience, Department of Molecular and Human Genetics, Graduate Programs in Developmental Biology, Graduate Program in Translational Biology and Molecular Medicine
- Baylor College of Medicine
- Houston, Texas, United States
- Caroline DeLuca Scholar
- Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital
- Houston, Texas, United States
- Post-Doctoral Fellowship at University of California, San Diego
- PhD from Baylor College of Medicine
- BS from Fudan University
Honors & Awards
- 2018 McKnight Scholar Award
- 2016 NARSAD Young Investigator Award
- 2015 Janett Rosenberg Trubatch Career Development Award
- 2015 Whitehall Foundation Award
- 2014 Caroline DeLuca Scholar
- 2010 Jane Coffin Childs Memorial Fund for Medical Research Fellowship
- 2009 Peter and Patricia Gruber International Research Award in Neuroscience
- 2001 Chun-Tsung Scholar
- Cortical circuit function and development in health and disease
In the mammalian brain, synaptic connections organize the vast number of neurons into intricate neural circuits that give rise to the senses, cognition, and actions. To understand how the brain performs its remarkable functions, it is essential to discover how the synapses orchestrate the spatiotemporal patterns of neuronal activities. Furthermore, synaptic dysfunction is being increasingly recognized as a critical underlying etiology of many neurological disorders, such as epilepsy and autism. Thus, my long-term research goal is to elucidate the synaptic mechanisms of neural circuits, understand the circuit dysfunctions in neurodevelopmental disorders, and harness this knowledge to explore new therapeutic strategies for these disorders.
The first research direction focuses on the relationship between synaptic excitation and inhibition (i.e., E/I ratio) in the cerebral cortex. E/I ratio is fundamental to many functional properties of cortical neurons, such as feature selectivity, spike timing, gain, and dynamic range. We aim to map the spatiotemporal distribution of E/I ratios in distinct types of cortical neurons and determine the contributing excitatory and inhibitory circuits. We also aim to elucidate the activity-dependent processes and molecular mechanisms that establish and maintain proper E/I ratios for different cell types.
The second research direction focuses on the genetic causes and mouse models of neurodevelopmental disorders. We collaborate with physicians and geneticists to identify new genetic causes of pediatric epilepsy and autism. We model these disorders in mice and use the mouse models to elucidate the pathophysiology and test therapeutic interventions. For example, we have created two mouse models of STXBP1 encephalopathy, a devastating neurodevelopmental disorder manifested with intellectual disability and epilepsy. These mouse models recapitulate key human phenotypes (Chen et al., 2019) and we will use them to identify the synaptic deficits underlying the pathological neural activity and explore gene therapy strategies.
Finally, we develop new technologies and integrate them into the above-mentioned research directions. For example, we improved light-activated chloride channels (e.g., GtACR2) for optogenetic inhibition (Messier et al., 2018). We are also developing a deep-learning algorithm to recognize and classify various EEG signals to facilitate our epilepsy studies.
A wide variety of approaches are employed in the laboratory including molecular manipulations (e.g. transgenic mouse, recombinant virus), functional manipulations (e.g. opto-genetics, chemical-genetics), structural and functional analyses (e.g. in vitro and in vivo electrophysiology, two-photon imaging), whole genome sequencing, gene expression profiling, neurobehavioral assays, and computation. Through these research endeavors, we are poised to elucidate the synaptic basis of neural circuits and bridge the gap between molecular mechanisms and brain functions at the circuit level.
- Chen W, Cai ZL, Chao ES, Chen H, Hao S, Chao HT, Kim JH, Messier JE, Zoghbi HY, Tang J, Swann JW, Xue M. "Stxbp1/Munc18-1 haploinsufficiency in mice recapitulates key features of STXBP1 encephalopathy and impairs cortical inhibition." bioRxiv. 2019
- Messier JE, Chen H, Cai ZL, Xue M. "Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon." Elife. 2018 August 9;7:e38506 Pubmed PMID: 30091701
- Xue M, Atallah BV, Scanziani M. "Equalizing excitation-inhibition ratios across visual cortical neurons.." Nature. 2014 July 31;511(7511):596-600. Pubmed PMID: 25043046
- "All Publications."
- R01 Research Grant
- National Institutes of Health/National Institute of Mental Health
- McKnight Scholar Award
- McKnight Endowment Fund for Neuroscience
- NARSAD Young Investigator Award
- Brain & Behavior Research Foundation
- R01 Research Grant
- National Institutes of Health/National Institute of Neurological Disorders and Stroke