Department of Neuroscience

Research Abstract

Transcription regulation is essential for the development and proper function of mammalian brains. During development transcription factors have been shown to play important roles in neuronal morphogenesis, for example, neuronal polarization, cell migration, axon growth and pathfinding. In addition, both spontaneous and sensory-driven neural activity are essential for guiding the process of synapse development which requires concerted regulation of a set of activity-dependent transcription factors that coordinate a program of gene expression. Mutations in components of the transcriptional program have been linked to human neurological and cognitive disorders. Understanding transcriptional regulatory network is key to understanding brain function in normal and diseased states, and could potentially open up new strategies for treating those diseases. My laboratory is interested in understanding the regulatory networks that control the development and proper function of mammalian brains in the context of human health and disease. In particular, we are interested in the following questions:

1. Transcription factor binding motif and cis-regulatory module discovery. We apply computational tools and develop new algorithms to predict regulatory motifs and modules that are important for brain development and function.
2. The relationship between transcription regulation and chromatin structure and modification as well as histone modifications. We apply machine learning algorithms to study the interaction between regulatory motifs and modules and DNA methylation, histone modifications as well as their effect on gene expression. Dysregulation of any of the components could cause mis- regulation of nearby genes therefore contributing to the development of neurological or cognitive disorders.

We take advantage of available big data sets from genomic and epigenomic studies and use computational and systems biology approaches to investigate the biology. We also have an interest in testing and developing software for analyzing high-throughput genomics data, including RNA-Seq, ChIP-seq and single cell RNA-seq data.

Selected Publications

• Zhao G, Vatanen T, Droit L, Park A, Kostic AD, Poon TW, Vlamakis H, Siljander H, Härkönen T, Hämäläinen AM, Peet A, Tillmann V, Ilonen J, Wang D, Knip M, Xavier RJ, Virgin HW. Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children. Proc Natl Acad Sci U S A. 2017; 114(30):E6166-E6175.
• Zhao G, Wu G, Lim ES, Droit L, Krishnamurthy S, Barouch DH, Virgin HW, Wang D. VirusSeeker, a computational pipeline for virus discovery and virome composition analysis. Virology. 2017: 18(503):21-30.
• Zhao G, Krishnamurthy S, Cai Z, Popov VL, Travassos da Rosa AP, Guzman H, Cao S, Virgin HW, Tesh RB, Wang D., Identification of novel viruses using VirusHunter--an automated data analysis pipeline. PLoS One. 2013: 8(10):e78470.
• Zhao G.*, Handley S.A*., Thackray L.B.*, Presti R., Miller A.D., Droit L., Abbink P., Maxfield L.F., Kambal A., Duan E., Stanley K., Kramer J., Macri S.C., Permar S.R., Schmitz J.E., Mansfield K., Brenchley J.M., Veazey R.S., Stappenbeck T.S., Wang D., Barouch D.H., and Virgin H.W. Pathogenic Simian Immunodeficiency Virus Infection Is Associated with Expansion of the Enteric Virome, Cell 2012: 151: 1–14.
• Zhao G., Ihuegbu N., Lee M., Schriefer L., Wang T. and Stormo G.D., Conserved Motifs and Prediction of Regulatory Modules in Caenorhabditis elegans, G3: Genes, Genomes, Genetics. 2012: 2(4): 469-481.
• Zhao G, Schriefer L, Stormo GD, Identification of muscle-specific regulatory modules in Caenorhabditis elegans. Genome Research 2007: 17(3): 348-57.
• Zhao G, Boekhoff-Falk G, Wilson BA, Skeath JB, Linking pattern formation to cell-type specification – Dichaete and Ind directly repress achaete gene expression in the Drosophila CNS. Proc. Natl. Acad. Sci. USA. 2007: 104(10): 3847-52.
• Zhao G, Wheeler SR and Skeath JB, Genetic control of DV patterning and neuroblast specification in the Drosophila CNS, Int. J. Dev. Biol. 2007: 51(2): 107-15
• Zhao G and Skeath JB, The Sox-domain containing gene Dichaete/fish-hook acts in concert with vnd and ind to regulate cell fate in the Drosophila neuroectoderm. Development 2002: 129(5): 1165-74.

For a complete list of Dr. Zhao's publications, click here.