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Chaolin Zhang, PhD

Academic Appointments

  • Assistant Professor of Systems Biology (in Biochemistry and Molecular Biophysics and in the Motor Neuron Center)
Chaolin Zhang, PhD

The Chaolin Zhang lab works at the interface of Systems Biology, RNA biology and Molecular Neuroscience to understand the organizational principles and functional impact of RNA regulatory networks in the nervous system. Regulation of RNA processing is dictated by interaction of at least several hundred RNA-binding proteins (RBPs) with their target transcripts. These interactions have a profound impact on the output of the transcriptome, specifically for the development and function of the nervous system.

To study RNA regulatory networks in motor neurons, we utilize CRISPR genome engineering technology in in vivo and in vitro model systems combined with high-throughput biochemical and molecular biology assays that profile transcriptomes and protein-RNA interactomes. We apply these assays to specific neuronal RBPs and intersect them with statistical and machine learning approaches to identify exons under cell type-specific regulation and predict specific protein-RNA interactions at single nucleotide resolution. We have developed an integrative modeling approach to combine multiple modalities of data to infer direct and functional targets of specific RBPs with high accuracy and sensitivity.

Our current studies focus on investigating systematically how multiple RBPs work together to achieve dynamic regulation during neurodevelopment (e.g., differentiation of spinal motor neurons from embryonic stem cells). We are also interested in mutations that disrupt RNA regulation observed in several neuronal diseases. Our work relies heavily on high-throughput technologies which produce an enormous amount of data and on algorithms, developed in the Zhang lab, to transform the acquired data into useful information. Ultimately, the goal is to better understand how the interplay between RNA regulation and RBPs may play a role in the development of various neuronal diseases.

The Chaolin Zhang lab works at the interface of Systems Biology, RNA biology and Molecular Neuroscience to understand the organizational principles and functional impact of RNA regulatory networks in the nervous system. Regulation of RNA processing is dictated by interaction of at least several hundred RNA-binding proteins (RBPs) with their target transcripts. These interactions have a profound impact on the output of the transcriptome, specifically for the development and function of the nervous system.

To study RNA regulatory networks in motor neurons, we utilize CRISPR genome engineering technology in in vivo and in vitro model systems combined with high-throughput biochemical and molecular biology assays that profile transcriptomes and protein-RNA interactomes. We apply these assays to specific neuronal RBPs and intersect them with statistical and machine learning approaches to identify exons under cell type-specific regulation and predict specific protein-RNA interactions at single nucleotide resolution. We have developed an integrative modeling approach to combine multiple modalities of data to infer direct and functional targets of specific RBPs with high accuracy and sensitivity.

Our current studies focus on investigating systematically how multiple RBPs work together to achieve dynamic regulation during neurodevelopment (e.g., differentiation of spinal motor neurons from embryonic stem cells). We are also interested in mutations that disrupt RNA regulation observed in several neuronal diseases. Our work relies heavily on high-throughput technologies which produce an enormous amount of data and on algorithms, developed in the Zhang lab, to transform the acquired data into useful information. Ultimately, the goal is to better understand how the interplay between RNA regulation and RBPs may play a role in the development of various neuronal diseases.

Departmental Appointments

  • Department of Biochemistry and Molecular Biophysics
  • Department of Systems Biology (Columbia University)

Centers/Institutes/Programs

  • Herbert Irving Comprehensive Cancer Center

Lab Locations

Research Interests

  • Axon pathfinding and synaptogenesis
  • Cell specification and differentiation
  • Neural degeneration and repair
  • Stem cell biology

NIH Grants

  • RNA-MEDIATED MECHANISMS OF MOTOR SYSTEM DYSFUNCTION IN SPINAL MUSCULAR ATROPHY (Federal Gov)

    Jun 1 2017 - Feb 28 2022

    : CLIP TOOL KIT (CTK): PIPELINE, USER INTERFACE AND TUTORIALS FOR CLIP DATA ANALYSIS (Federal Gov)

    Apr 10 2017 - Mar 31 2019

    TOWARD UNDERSTANDING AGING MECHANISMS OF NEUROMUSC (Federal Gov)

    Sep 30 2016 - May 31 2018

    SYSTEMATIC FUNCTIONAL DISSECTION OF NEURONAL TRANSCRIPTOME DIVERSITY (Federal Gov)

    May 15 2016 - Apr 30 2018

    ELUCIDATING PATHOGENIC MUTATIONS DISRUPTING RNA REGULATION IN AUTISM (Private)

    Sep 1 2014 - Aug 31 2017

    AN INTEGRATIVE GENOMIC STRATEGY TO INFER GLOBAL RNA REGULATORY NETWORKS (Federal Gov)

    Feb 21 2011 - Nov 30 2016

    INTRON RETENTION IN THE MAMMALIAN TRANSCRIPTOME (Private)

    Oct 27 2014 - Apr 26 2015

    MODELING ALTERATION OF RBFOX1 (A2BP1) TARGET NETWORK IN AUTISM (Private)

    Oct 1 2013 - Sep 30 2014

Publications

Feng, H., Zhang, X., Zhang, C., 2015. mRIN for direct assessment of genome-wide and gene-specific mRNA integrity from large-scale RNA sequencing data. Nat Comm. 6:7816. doi: 10.1038/ncomms8816.

Yan, Q., Weyn-Vanhentenryck, S.M.,Wu, J., Sloan, S.A., Zhang, Y., Chen, K., Wu, J.-Q., Barres, B.A., Zhang, C., 2015. Systematic discovery of regulated and conserved alternative exons in the mammalian brain reveals NMD modulating chromatin regulators. Proc. Nat. Acad. Sci. USA. Mar 3. pii: 201502849.

Weyn-Vanhentenryck, S.M., Mele,A., Yan,Q., Sun,S., Farny,N., Zhang,Z., Xue,C., Herre,M., Silver,P.A., Zhang, M.Q., Krainer,A.R., Darnell,R.B. , Zhang,C.  2014. HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism. Cell Rep. 10.1016/j.celrep.2014.02.005.

Moore, M., Zhang, C., Gantman, E.C., Mele, A., Darnell, J.C., Darnell, R.B. 2014. Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis. Nat Protocols, 9:263-293.

Zhang, C., Lee, K.-Y., Swanson, M.S., Darnell, R.B. 2013. Prediction of clustered RNA-binding protein motif sites in the mammalian genome. Nucleic Acids Res. 41:6793-6807.

Wu,J., Anczukow, O., Krainer, A.R., Zhang,M.Q. , Zhang,C. , 2013. OLego: Fast and sensitive mapping of spliced mRNA-Seq reads using small seeds. Nucleic Acids Res. 41:5149-5163.

Darnell, J.C., Van Driesche, S.J., Zhang,C., Hung, K.Y.S., Mele, A., Fraser, C.E., Stone, E.F., Chen, C., Fak, J.J., Chi, S.W., Licatalosi, D.D., Richter, J.D., Darnell, R.B., 2011. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell, 146:247-261.

Zhang,C., Darnell, R.B. 2011. Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data. Nat. Biotech. 29:607-614.

Zhang,C., Frias, M.A., Mele, A., Ruggiu, M., Eom, T., Marney, C.B., Wang, H., Licatalosi, D.D., Fak, J.J., Darnell, R.B. 2010. Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science. 329: 439-443.

Zhang,C., Zhang, Z., Castle, J., Sun, S., Johnson, J., Krainer, A.R. and Zhang, M.Q. 2008. Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Genes Dev. 22:2550-2563.