The Faculty

Focus

The Tang group aims to combine the CRISPR technology with protein engineering to develop a targeted in situ DNA diversification tool, enabling the construction of complex synthetic memories in live cells for single-cell lineage tracing

Biography

Tsinghua University, BS, Chemistry and Biology, 2009

University of Illinois at Urbana-Champaign, PhD, Chemistry, 2015

Postdoctoral Fellow, Broad Institute of Harvard and MIT, 2015-19

Assistant Professor, University of Chicago, 2019-

Accolades and honors

2019 - Neubauer Family Assistant Professorship  

2016-19 Jane Coffin Childs Memorial Fund for Medical Research Fellowship  

Research Interests

Biotechnologies have advanced to a stage where we can understand in exquisite detail the internal state of a cell. Far fewer tools have been developed that can record a cell’s history and explain how this history dictates its present and future states. For example, lineage tracing can uncover a cell’s origin and provide crucial insights into tissue development and homeostasis, yet traditional lineage tracing approaches offer only a low resolution history of the cell and cannot be applied to optically opaque tissues or physically inaccessible contexts that prevent the use of imaging techniques. The Tang group aims to combine the CRISPR technology with protein engineering to develop a targeted in situ DNA diversification tool, enabling the construction of complex synthetic memories in live cells for single-cell lineage tracing.

Drug development by constructing and screening highly functionalized cyclic peptide libraries

Peptides are extremely potent protein-protein interaction modulators and protein function regulators owing to their ability to recognize solvent-exposed, flat protein surfaces. Cyclic peptides are particularly promising as they can bind to target biomolecules with improved affinity and specificity and are less susceptible to protease degradation. Motivated by their therapeutic potential, the Tang group constructs highly functionalized cyclic peptide libraries using a novel route, taking advantage of the biosynthetic machinery of ribosomal natural products. Using a droplet-based selection system, these libraries will be screened for activities of interest in disease-relevant cell models, thereby realizing the ultimate therapeutic potential of peptide natural products.

Sulfur modifications in DNA and RNA and their mechanisms of formation

Chemically modified bases are ubiquitously found in organisms and play essential roles in biology. As the sixth most abundant element in living organisms, sulfur has been identified in both RNA and DNA. However, the distribution patterns and the mechanisms of formation for these modifications are not fully understood. The Tang lab develops modification-sensitive sequencing techniques to map known and novel sulfur modifications in DNA and RNA at the base resolution. The Tang group also studies the mechanisms of formation as well as the regulatory roles of sulfur modification in nucleotides, aiming to broaden the current understanding of epigenetics and epitranscriptomics. Finally, as a biotechnological tool, bases contain sulfur modifications will be applied as labeling probes to study genome and transcriptome dynamics.

Selected Publications

Bobeica SC, Zhu L, Acedo JZ, Tang W, van der Donk WA*. Structural determinants of macrocyclization in substrate-controlled lanthipeptide biosynthetic pathways. Chem. Sci. 2020, in press

Tang W, Liu DR*. Rewritable multi-event analog recording in bacterial and mammalian cells. Science 2018, 360, eaap8992

Hu JH, Miller SM, Geurts MH, Tang W, Chen L, Sun N, Zeina C, Gao X, Rees HA, Lin Z, Liu DR*. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature 2018, 556, 57–63

Tang W, Bobeica SC, Wang L, van der Donk WA*. CylA is a sequence-specific protease involved in toxin biosynthesis. J. Ind. Microbiol. Biotechnol. 2018, doi.org/10.1007/s10295-018-2110-9

Tang W, Hu JH, Liu DR*. Aptazyme-embedded guide RNAs enable ligand-responsive genome engineering. Nat. Commun. 2017, 8, 15939

Tang W, Thibodeaux GN, van der Donk WA*. The enterococcal cytolysin synthetase coevolves with substrate for stereoselective lanthionine synthesis. ACS Chem. Biol. 2016, 11, 2438-2446

Dong SH#, Tang W#, Lukk T, Nair SK*, van der Donk WA*. The enterococcal cytolysin synthetase has an unanticipated lipid kinase fold. eLife 2015, 4, 07607 (# equal contribution)

Tang W, Jiménez-Osés G, Houk KN*, van der Donk WA*. Substrate control in stereoselective lanthionine biosynthesis. Nat. Chem. 2015, 7, 57-64

Tang W, Dong SH#, Repka LM, He C, Nair SK*, van der Donk WA*. Applications of the class II lanthipeptide protease LicP for sequence-specific, traceless peptide bond cleavage. Chem. Sci. 2015, 6, 6270-6279 (# equal contribution)

Tang W, van der Donk WA*. The sequence of the enterococcal cytolysin imparts unusual lanthionine stereochemistry. Nat. Chem. Biol. 2013, 9, 157-159

Tang W, van der Donk WA*. Structural characterization of four prochlorosins: a novel class of lantipeptides produced by planktonic marine cyanobacteria. Biochemistry 2012, 51, 4271-4279