Our lab studies the genetic and neuronal mechanisms underlying developmental brain disorders including intellectual disability (ID) and autism spectrum disorders (ASDs) and in developing effective treatment for these disorders.
To systematically identify novel disease-causing genes for X-linked ID (XLID), we use high-throughput genomic approaches including X-chromosome cDNA microarray and next-generation sequencing to screen all known genes and functional elements on human X chromosome in XLID patients. We study mechanisms of novel XLID genes using in vitro and neuronal assays, electrophysiology and mutant mouse models. Current projects are focused on characterizing novel XLID candidate genes involving glutamate-signaling pathway, and phosphorylation and palmitoylation of key neuronal proteins.
To understand mechanisms of synaptic dysfunction in ASDs, we sequence genes encoding all known synaptic proteins, synaptome, in patients to identify causal and risk variants. We conduct functional studies of these variants using in vitro and neuronal assays, electrophysiology and mutant mouse models. One current focus is to understand glutamate-signaling disturbance in social dysfunction in ASDs.
Niranjan TS, May M, Skinner C, Turner T, Rose R, Stevenson R, Schwartz CE, Wang T. “Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes” PLoS ONE. 2015 Feb 13;10(2):e0116454.
Ngoh A, Mctague A, Wentzensen IM, Meyer E, Applegate C, Kossoff EH, Batista DA, Wang T, Kurian MA. “Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum.” Dev Med Child Neurol. 2014 Nov;56:1124-8.
Basehore MJ, Michaelson-Cohen R, Levy-Lahad E, Sismani C, Bird L, Friez MJ, Walsh TJ, Abidi F, Holloway L, Skinner C, McGee S, Alexandrou A, Syrrou M, Patsalis PC, Wang T, Schwartz CE, King MC, Stevenson RE. “Alpha-thalassemia intellectual disability: variable phenotypic expression among males with the p.R37X mutation.” Clinic Genet. 2015 May;87(5):461-6.
Adamczyk A, Mejias R. Takamiya K, Yocum J, Krasnova N, Calderon J, Cadet JL, Huganir R, Pletnikov M, and Wang T (2012) “GluA3-deficiency in mice is associated with increased social and aggressive behavior and elevated dopamine in striatum.” Behav Brain Res. 2012 Apr 1;229:265.
Pirooznia M, Wang T, Avramopoulos D, Valle D, Thomas G, Huganir R, Goes FS, Potash JB, Zandi PP. “SynaptomeDB: an ontology-based knowledgebase for synaptic genes.” Bioinformatics. 2012 Mar 15;28(6):897.