|Assistant Professor, Pediatrics and Institute of Genetic Medicine|
|Contact | Research Interests | Publications|
We are interested in 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.
ID is a common disability affecting 2-3% of the general population. Genetic defects have a major contribution to the causes of ID. To systematically identify novel disease-causing genes for X-linked ID (XLID), we utilize 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 characterization of novel XLID candidate genes involving glutamate-signaling pathway, and phosphorylation and palmitoylation of key neuronal proteins.
ASDs are highly heritable neurobehavioral disorders affecting communication and social interactions. ASDs are found in 1 in 110 children in the US with affected male to female ratio of 4:1. Synapse is the fundamental structure for brain function through its roles in connecting neurons into circuits. 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.
1. Zhang L, Jie C, Obie, C, Schwartz C, Valle D, and Wang T (2007). Identification of a functional promoter polymorphism in PLP2 in XLMR patients using an X-chromosome cDNA microarray. Genome Res 17:641
2. Wu Y, Arai AC, Rumbaugh G, Srivastava AK, Turner G, Hayashi T, Suzuki E, Jiang Y, Zhang L, Rodriguez J, Boyle J, Tarpey P, Raymond FL, Nevelsteen J, Froyen G, Stratton M, Futreal A, Gecz J, Stevenson, R, Schwartz, CE, Valle D, Huganir RL, Wang T (2007). Mutations in ionotropic glutamate receptor 3 alter channel function and are associated with moderate cognitive impairment in humans. Proc Natl Acad Sci USA 104:18163
3. Sobreira N, Walsh MF, Batista D, Wang T (2009). Interstitial deletion 5q14.3-q21 associated with iris coloboma, hearing loss, dental anomaly, moderate intellectual disability, and attention deficit and hyperactivity. Am J Med Genet 149A:2581
4. Wang Y, Adamczyk A, Shugart YY, Samuels JF, Grados MA, Greenberg BD, Knowles JA, McCracken, JT, Rauch SL, Murphy DL, Rasmussen SA, Cullen B, Pinto A, Fyer AJ, Piacentini J, Pauls DL, Bienvenu OJ, Riddle M, Liang KY, Valle D, Wang T, Nestadt G (2010) SLC1A1 sequence variants in OCD. Neuropsychiatr Genet 153B:675
5. Huang CR, Schneider AM, Lu Y, Niranjan T, Shen P, Robinson MA, Steranka JP, Valle D, Civin CI, Wang T, Wheelan SJ, Ji HK, Boeke JD, and Burns KH (2010). TIP-chip reveals that interspersed repeats are major structural variants in the human genome. Cell 141:1171.
6. Li F, Batista D, Maumenee, IH, and Wang T (2010). An unbalanced translocation between chromosomes 2p and 6p associated with Axenfeld-Rieger Anomaly, hearing loss, developmental delay, and distinct facial dysmorphism. Am J Med Genet 152A:1318
7. Adamczyk A, Gause CD, Sattler R, Vidensky S, Rothstein JD, Singer HS, and Wang T (2010). A functional missense variant in glutamate transporter EAAT1, in Tourette syndrome. Psychiatr Genet 43:61.
8. Raymond G, Wohler E, Dinsmore C, Cox J, Johnston M, Batista D, Wang T (2011) An Interstitial duplication at 2q24.3 involving SCN1A, SCN2A, SCN3A genes associated with infantile epilepsy. Am J Med Genet 155A:920
9. Mejias R, Adamczyk A, Anggono V, Niranjan T, Thomas GT, Sharma K, Skinner C, Schwartz CE, Stevenson R, Fallin MD, Kaufmann WE, Pletnikov M, Valle D, Huganir RL, and Wang T (2011). Gain-of-function GRIP1 Variants Alter GluR2 Recycling and Surface Distribution in Autism. Proc Natl Acad Sci USA 108:4920.
10. Niranjan T, Adamczyk A, Corrada-Bravo H, Taub MA, Wheelan S, Irizarri, R, and Wang T (2011). Effective Detection of Rare Variants in Pooled DNA Samples using Cross-Pool Tailcurve Analysis. Genome Biol 12:R93
11. Pirooznia M, Wang T, Avramopoulos D, Valle D, Thomas G, Huganir R, Goes FS, Potash JB, Zandi PP (2012). SynaptomeDB: an ontology-based knowledgebase for synaptic genes. Bioinformatics Epub
12. 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 Epub.
Tao Wang, MD, PhD
733 North Broadway
Broadway Research Building
Baltimore MD 21205