Hsiao-Tuan Chao

Hsiao-Tuan Chao

Research Interests

The advent of whole-exome and whole-genome sequencing has contributed to enormous advances in the diagnosis of rare diseases, with a large proportion of disease genes identified to impact the formation and function of the nervous system. However, with the rapid rate of disease gene discovery we are now faced with increasing numbers of rare variants identified in poorly characterized genes.

I am interested in utilizing human sequencing data and Drosophila melanogaster for high-throughout identification and analysis of the fundamental biology of novel genes mediating the pathogenesis of autism spectrum disorders with co-morbid epilepsy. In the absence of overt structural brain malformations, these disorders likely result from dysfunction on a microstructural or cellular level impacting circuit formation and synaptic transmission. Utilizing these disorders to identify pathogenic gene variants and gene networks will provide critical information regarding the formation of neural circuits, regulatory mechanisms of circuit function and synaptic transmission, and potentially open new avenues for therapeutic intervention.


Wangler MF, Yamamoto S, Chao HT, Posey JE, Westerfield M, Postlethwait J, Members of the Undiagnosed Diseases Network (UDN), Hieter P, Boycott KM, Campeau PM, Bellen HJ (2017) Model organisms facilitate rare disease diagnosis and therapeutic research. Genetics 207:9-27.  [Abstract]
Chao HT*, Liu L*, Bellen HJ (2017) Building dialogues between clinical and biomedical research through cross-species collaborations. Seminars in Cell and Developmental Biology 70:49-57. (*equal contribution) [Abstract]
Wang J, Al-Ouran R, Hu Y, Kim SY, Wan YW, Wangler MF, Yamamoto S, Chao HT, Comjean A, Mohr SE, UDN Consortium, Perrimon N, Liu Z, Bellen HJ (2017) MARRVEL: integration of human and model organism genetic resources to facilitate functional annotation of the human genome. American Journal of Human Genetics 100:843-853.  [Abstract]
Chao HT*, Davids M*, Burke E, Pappas JG, Rosenfeld JA, McCarty AJ, Davis T, Wolfe L, Toro C, Tifft C, Xia F, Stong N, Johnson TK, Warr CG; Undiagnosed Diseases Network, Yamamoto S, Adams DR, Markello TC, Gahl WA, Bellen HJ, Wangler MF, Malicdan MC (2017) A syndromic neurodevelopmental disorder caused by de novo variants in EBF3. American Journal of Human Genetics 100:128-137. (*equal contribution) [Abstract]
Chang CL, Trimbuch T, Chao HT, Jordan JC, Herman M, Rosenmund C (2014) Investigation of synapse formation and function in a Glutamatergic-GABAergic two-neuron microcircuit. Journal of Neuroscience 34:855-868.  [Abstract]
Jiang M, Ash RT, Baker SA, Suter B, Ferguson A, Park J, Rudy J, Torsky SP, Chao HT, Zoghbi HY, Smirnakis SM (2013) Dendritic arborization and spine dynamics are abnormal in the mouse model of MECP2 duplication syndrome. Journal of Neuroscience 33:19518-19533.  [Abstract]
Chao HT, Zoghbi HY (2012) MeCP2: only 100% will do. Nature Neuroscience 15:176-177.  [Abstract]
Wagnon JL, Mahaffey CL, Sun W, Yang Y, Chao HT, Frankel WN (2011) Etiology of a genetically complex seizure disorder in Celf4 mutant mice. Genes, Brain and Behavior 10:765-777.  [Abstract]
Chao HT, Chen H, Samaco RC, Xue M, Chahrour M, Yoo J, Neul JL, Gong S, Heintz N, Ekker M, Rubenstein J, Noebels JL, Rosenmund C, Zoghbi HY (2010) MeCP2 deficiency in GABAergic neurons mediates abnormal social behavior and key features of Rett syndrome. Nature 468:263-269.  [Abstract]
Xue M, Craig TK, Xu J, Chao HT, Rizo J, Rosenmund C (2010) Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity. Nature Structural & Molecular Biology 17:568-575.  [Abstract]
Samaco RC, Mandel-Brehm C, Chao HT, Fyffe SL, Sun Y, Ren J, Hyland K, Maricich SM, Deneris ES, Greer JJ, Humphreys P, Percy A, Glaze DG, Thaller C, Zoghbi HY, Neul JL (2009) Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities. Proceedings of the National Academy of Sciences USA 106:21966-21971.  [Abstract]
Rose MF, Ren J, Ahmad KA, Chao HT, Klisch TJ, Flora A, Greer JJ, Zoghbi HY (2009) Math1 is essential for the development of hindbrain neurons critical for perinatal breathing. Neuron 64:341-354.  [Abstract]
Chao HT, Zoghbi HY (2009) The yin and yang of MeCP2 phosphorylation . Proc Natl Acad Sci 106:4577-4578.  [Abstract]
Fyffe SL, Neul JL, Samaco RC, Chao HT, Ben-Shachar S, Moretti P, McGill BE, Goudling EH, Sullivan E, Tecott LH, Zoghbi HY (2008) Deletion of Mecp2 in Sim1-expressing neurons reveals a critical role for MeCP2 in feeding behavior, anxiety, and aggression. Neuron 59:947-958.  [Abstract]
Samaco RC, Fryer JD, Ren J, Fyffe S, Chao HT, Sun Y, Greer JJ, Zoghbi HY, Neul JL (2008) A partial loss of function allele of methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome. Human Molecular Genetics 17:1718-1727.  [Abstract]
Chao HT, Zoghbi HY, Rosenmund C (2007) MeCP2 controls synaptic strength in glutamatergic neurons by regulating synapse number. Neuron 56:58-65.  [Abstract]
Xue M, Reim K, Chen X, Chao HT, Deng H, Rizo J, Brose N, Rosenmund C (2007) Distinct domains of Complexin I differentially regulate neurotransmitter release. Nature Structural & Molecular Biology 14:949-958.  [Abstract]