Bio

Honors & Awards


  • Best Poster Award, Gordon Research Seminars, Post-Transcriptional Gene Regulation (2016)
  • Early Career Award, FASEB Science Research Conference (2019)

Professional Education


  • Master of Arts, Harvard University (2017)
  • Bachelor of Science, University of Science and Technology of China, Physics/Optics (2013)
  • Doctor of Philosophy, Harvard University, Chemistry (2020)

Stanford Advisors


Patents


  • Guiping Wang, Xiaowei Zhuang, Jeffrey R. Moffitt. "United StatesMultiplexed imaging using merfish, expansion microscopy, and related technologies (pending)", Harvard College

Research & Scholarship

Lab Affiliations


Publications

All Publications


  • Structural plasticity of actin-spectrin membrane skeleton and functional role of actin and spectrin in axon degeneration. eLife Wang, G., Simon, D. J., Wu, Z., Belsky, D. M., Heller, E., O'Rourke, M. K., Hertz, N. T., Molina, H., Zhong, G., Tessier-Lavigne, M., Zhuang, X. 2019; 8

    Abstract

    Axon degeneration sculpts neuronal connectivity patterns during development and is an early hallmark of several adult-onset neurodegenerative disorders. Substantial progress has been made in identifying effector mechanisms driving axon fragmentation, but less is known about the upstream signaling pathways that initiate this process. Here, we investigate the behavior of the actin-spectrin-based Membrane-associated Periodic Skeleton (MPS), and effects of actin and spectrin manipulations in sensory axon degeneration. We show that trophic deprivation (TD) of mouse sensory neurons causes a rapid disassembly of the axonal MPS, which occurs prior to protein loss and independently of caspase activation. Actin destabilization initiates TD-related retrograde signaling needed for degeneration; actin stabilization prevents MPS disassembly and retrograde signaling during TD. Depletion of βII-spectrin, a key component of the MPS, suppresses retrograde signaling and protects axons against degeneration. These data demonstrate structural plasticity of the MPS and suggest its potential role in early steps of axon degeneration.

    View details for PubMedID 31042147

  • Multiplexed imaging of high-density libraries of RNAs with MERFISH and expansion microscopy SCIENTIFIC REPORTS Wang, G., Moffitt, J. R., Zhuang, X. 2018; 8: 4847

    Abstract

    As an image-based single-cell transcriptomics approach, multiplexed error-robust fluorescence in situ hybridization (MERFISH) allows hundreds to thousands of RNA species to be identified, counted and localized in individual cells while preserving the native spatial context of RNAs. In MERFISH, RNAs are identified via a combinatorial labeling approach that encodes RNA species with error-robust barcodes followed by sequential rounds of single-molecule FISH (smFISH) to read out these barcodes. The accuracy of RNA identification relies on spatially separated signals from individual RNA molecules, which limits the density of RNAs that can be measured and makes the multiplexed imaging of a large number of high-abundance RNAs challenging. Here we report an approach that combines MERFISH and expansion microscopy to substantially increase the total density of RNAs that can be measured. Using this approach, we demonstrate accurate identification and counting of RNAs, with a near 100% detection efficiency, in a ~130-RNA library composed of many high-abundance RNAs, the total density of which is more than 10 fold higher than previously reported. In parallel, we demonstrate the combination of MERFISH with immunofluorescence in expanded samples. These advances increase the versatility of MERFISH and will facilitate its application to a wide range of biological problems.

    View details for DOI 10.1038/s41598-018-22297-7

    View details for Web of Science ID 000427688100040

    View details for PubMedID 29555914

    View details for PubMedCentralID PMC5859009

  • High-throughput single-cell gene-expression profiling with multiplexed error-robust fluorescence in situ hybridization PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Moffitt, J. R., Hao, J., Wang, G., Chen, K., Babcock, H. P., Zhuang, X. 2016; 113 (39): 11046–51

    Abstract

    Image-based approaches to single-cell transcriptomics, in which RNA species are identified and counted in situ via imaging, have emerged as a powerful complement to single-cell methods based on RNA sequencing of dissociated cells. These image-based approaches naturally preserve the native spatial context of RNAs within a cell and the organization of cells within tissue, which are important for addressing many biological questions. However, the throughput of these image-based approaches is relatively low. Here we report advances that lead to a drastic increase in the measurement throughput of multiplexed error-robust fluorescence in situ hybridization (MERFISH), an image-based approach to single-cell transcriptomics. In MERFISH, RNAs are identified via a combinatorial labeling approach that encodes RNA species with error-robust barcodes followed by sequential rounds of single-molecule fluorescence in situ hybridization (smFISH) to read out these barcodes. Here we increase the throughput of MERFISH by two orders of magnitude through a combination of improvements, including using chemical cleavage instead of photobleaching to remove fluorescent signals between consecutive rounds of smFISH imaging, increasing the imaging field of view, and using multicolor imaging. With these improvements, we performed RNA profiling in more than 100,000 human cells, with as many as 40,000 cells measured in a single 18-h measurement. This throughput should substantially extend the range of biological questions that can be addressed by MERFISH.

    View details for DOI 10.1073/pnas.1612826113

    View details for Web of Science ID 000383954700069

    View details for PubMedID 27625426

    View details for PubMedCentralID PMC5047202

  • Prevalent presence of periodic actin-spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA He, J., Zhou, R., Wu, Z., Carrasco, M. A., Kurshan, P. T., Farley, J. E., Simon, D. J., Wang, G., Han, B., Hao, J., Heller, E., Freeman, M. R., Shen, K., Maniatis, T., Tessier-Lavigne, M., Zhuang, X. 2016; 113 (21): 6029-6034

    Abstract

    Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens.

    View details for DOI 10.1073/pnas.1605707113

    View details for PubMedID 27162329

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