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Siyuan Steven Wang, Ph. D.

Jane Coffin Childs Post-doctoral Fellow
Zhuang Research Lab
Department of Chemistry and Chemical Biology
Department of Physics
Harvard University

Education

Ph. D., Department of Molecular Biology, Princeton University, 2007-2011.
B. S., Department of Physics, Peking University, 2003-2007.

New Positions Available

I will be joining the Department of Genetics at Yale University School of Medicine as a tenure-track assistant professor in September, 2017. My lab will use leading microscopy approaches and also invent new technologies to understand the structural organization of chromatin and how it impacts cellular state. Prospective postdoctoral fellows and students are welcome to contact me for positions in my lab. Direct recommendations from faculty members are also welcome and appreciated.

Research Experience

My main postdoctoral work in Professor Xiaowei Zhuang's lab at Harvard University has focused on understanding the spatial organization of mammalian chromatin. The spatial organization of chromatin in the nucleus is of critical importance to many essential genomic functions, from the regulation of gene expression to the replication of the genome. Unfortunately, relatively little is known about the three-dimensional (3D) organization of the chromatin beyond the length scale of the nucleosomes, in large part due to the lack of tools that allow direct visualization and comprehensive mapping of the 3D organization of chromatin in individual chromosomes. To address this need, my main postdoctoral work (published in Science, 2016) involves the development of a multiplexed DNA imaging method, via sequential fluorescence in situ hybridization (FISH). This novel method enables direct spatial tracing of numerous genomic regions in individual chromosomes in single cells, offering a powerful tool to study the 3D organization of chromatin. As the first application of this method, I studied the spatial organization of the recently discovered topologically associating domains (TADs), also termed contact domains, by tracing the 3D positions of TADs in individual chromosomes in interphase human cells, and revealed a series of unexpected structural features. This work opened up many opportunities to study the spatial organization of chromatin at different length scales in a variety of important biological processes and in diseases. We have also developed a highly-multiplexed RNA FISH technique that enabled localized detection and quantification of 1000 different RNA species in a single cell (published in Science, 2015). In comparison to single-cell RNA sequencing, this multiplexed FISH method easily retains the spatial information of all the probed transcripts, and is highly sensitive for counting low-copy-number transcripts. Additionally, I led the development of a new photoactivatable fluorescent protein (PAFP), named mMaple3 (published in PNAS, 2014), that outperforms previously existing PAFPs in single-molecule-based superresolution imaging (STORM/PALM) and has been adopted by more than 100 research labs around the world. This work also established the criteria for evaluating novel PAFPs for single-molecule-based superresolution imaging. My postdoctoral research was supported by a Jane Coffin Childs Fellowship, and was awarded with the 2016 International Union of Pure and Applied Physics Young Scientist Prize in Biological Physics (one recipient per year worldwide), and the 2017 Harvard Chinese Life Sciences Distinguished Research Award.

My graduate research, co-advised by Professor Ned Wingreen and Professor Joshua Shaevitz at Princeton University, focused on bacterial cell mechanics, especially on how the bacterial cytoskeleton coordinates cell wall synthesis. The first project in my dissertation (published in PNAS, 2010) showed that the bacterial actin homologue MreB contributes nearly as much to the rigidity of an E. coli cell as the peptidoglycan cell wall. This conclusion provided the premise for several theoretical works that assumed MreB applies force to the cell wall during growth, and suggested an evolutionary origin of cytoskeleton-governed cell rigidity. My second project (published in PNAS, 2011) dealt with the discovery of the motion of E. coli MreB linked to cell wall synthesis. This was the first observation of a cell-wall assembly driven molecular motor in bacteria. (Simultaneously with our work, Garner et al and Dominguez-Escobar et al discovered the same phenomenon in B. subtilis.) My third project (published in PNAS, 2012) elucidated that both cell wall synthesis and the peptidoglycan network have a chiral ordering, which is established by MreB. This work linked the molecular structures of the cytoskeleton and of the cell wall with organismal-scale behavior. My fourth project (published in Biophysical Journal, 2013) developed a generic, quantitative model to explain the various spatial patterns adopted by bacterial cytoskeletal proteins. The model set up a new theoretical framework for the study of membrane-polymer interaction, and is useful for the exploration of the physical limits of cytoskeleton organization. My dissertation won the 2011 American Physical Society Award for Outstanding Doctoral Thesis Research in Biological Physics (one recipient per year in the United States).

As an undergrad, I studied biological network dynamics in the Center for Theoretical Biology at Peking University under the direction of Professor Qi Ouyang.

Publications

[1] Siyuan Wang, Jun-Han Su, Brian J. Beliveau, Bogdan Bintu, Jeffrey R. Moffitt, Chao-ting Wu, Xiaowei Zhuang, Spatial organization of chromatin domains and compartments in single chromosomes, Science, Vol. 353, Issue 6299, 598-602, DOI: 10.1126/science.aaf8084, (2016). (HTML) Highlighted in F1000Prime.

[2] Siyuan Wang#, Jun-Han Su, Feng Zhang and Xiaowei Zhuang, An RNA-aptamer-based two-color CRISPR labeling system, Scientific Reports, Vol. 6, 26857, (2016). #Corresponding author. (HTML)

[3] Jeffrey R. Moffitt, Shristi Pandey, Alistair N. Boettiger, Siyuan Wang, Xiaowei Zhuang, Spatial organization shapes the turnover of a bacterial transcriptome, Elife, Vol. 5, e13065, (2016). (HTML)

[4] Alistair N. Boettiger, Bogdan Bintu, Jeffrey R. Moffitt, Siyuan Wang, Brian J. Beliveau, Geoffrey Fundenberg, Maxim Imakaev, Leonid A. Mirny, Chao-ting Wu, and Xiaowei Zhuang, Super-resolution imaging reveals distinct chromatin folding for different epigenetic states, Nature, Vol. 529, 418-422, (2016). (HTML)

[5] Kok Hao Chen, Alistair N. Boettiger, Jeffrey R. Moffitt, Siyuan Wang, and Xiaowei Zhuang, Spatially resolved, highly multiplexed RNA profiling in single cells, Science, DOI: 10.1126/science.aaa6090, (2015). (HTML) Highlighted in F1000Prime.

[6] Siyuan Wang, Jeffrey R. Moffitt, Graham T. Dempsey, X. Sunney Xie, and Xiaowei Zhuang, Characterization and development of photoactivatable fluorescent proteins for single-molecule¨Cbased superresolution imaging, PNAS, Vol. 111, No. 23, 8452-8457, (2014). (HTML) Highlighted in F1000Prime.

[7] Xinliang Xu, Hao Ge, Chan Gu, Yi Qin Gao, Siyuan S. Wang, Beng Joo Reginald Thio, James T. Hynes, X. Sunney Xie, and Jianshu Cao, Modeling spatial correlation of DNA deformation: DNA allostery in protein binding, The Journal of Physical Chemistry B, Vol. 117, 13378-13387, (2013). (HTML)

[8] Sangjin Kim, Erik Brostromer, Dong Xing, Jianshi Jin, Shasha Chong, Hao Ge, Siyuan Wang, Chan Gu, Lijiang Yang, Yi Qin Gao, Xiao-dong Su, Yujie Sun, and X. Sunney Xie, Probing Allostery Through DNA, Science, Vol. 339, 816-819, (2013). (PDF)

[9] Siyuan Wang and Ned S. Wingreen, Cell shape can mediate the spatial organization of the bacterial cytoskeleton, Biophysical Journal, Vol. 104, 541-552, (2013). (PDF)

[10] Siyuan Wang# and Joshua W. Shaevitz, The mechanics of shape in prokaryotes, Frontiers in Bioscience (Scholar Edition), Vol. 5, 564-574, (2013). #Corresponding author. (PDF)

[11] Siyuan Wang, Leon Furchtgott, Kerwyn Casey Huang, and Joshua W. Shaevitz, Helical insertion of peptidoglycan produces chiral ordering of the bacterial cell wall, PNAS, Vol. 109, No. 10, E595-E604, (2012). (PDF) (Author Summary)

[12] Siyuan Wang, Mechanics, dynamics and organization of the bacterial cytoskeleton and cell wall, Ph. D. Dissertation, Princeton University, (2011). (HTML)

[13] Sven van Teeffelen, Siyuan Wang, Leon Furchtgott, Kerwyn Casey Huang, Ned S. Wingreen, Joshua W. Shaevitz, and Zemer Gitai, The bacterial actin MreB rotates, and rotation depends on cell-wall assembly, PNAS, Vol. 108, No. 38, 15822-15827, (2011). (PDF) Highlighted by HFSP.

[14] Siyuan Wang, Hugo Arellano-Santoyo, Peter A. Combs, and Joshua W. Shaevitz, Actin-like cytoskeleton filaments contribute to cell mechanics in bacteria, PNAS, Vol. 107, No. 20, 9182-9185, (2010). (PDF)

[15] Siyuan Wang, Hugo Arellano-Santoyo, Peter A. Combs, and Joshua W. Shaevitz, Measuring the Bending Stiffness of Bacterial Cells Using an Optical Trap, JoVE, vol. 38, doi: 10.3791/2012, (2010). (HTML)

[16] Ming Ni*, Siyuan Wang*, and Qi Ouyang, Modelling the SOS response by semi-stochastic simulation, Chinese Physics Letters, Vol. 25, No. 7, 2702-2705, (2008). *Co-first authors. (PDF)

[17] Ming Ni, Siyuan Wang, Jikun Li, and Qi Ouyang, Simulating the temporal modulation of inducible DNA damage response in Escherichia coli, Biophysical Journal, Vol. 93, 62-73, (2007). (PDF)

[18] Siyuan Wang, Yuping Zhang, and Qi Ouyang, Stochastic model of coliphage lambda regulatory network, Physical Review E, Vol. 73, No. 041922, (2006). (PDF)


Last update: June 1, 2017.