Education

B.A., 1992, Tsinghua University
Ph.D., 1997, Tsinghua University

Honors and Awards

The ACS Memphis Section Southern Chemist Award, 2018; Russell Research Award for Science, Mathematics, and Engineering, 2017; South Carolina ACS Outstanding Chemist Award, 2016; Carolina Distinguished Professor, 2013;  Robert L. Sumwalt Professor of Chemistry, University of South Carolina, 2009-2013;  Fellow of the American Association for the Advancement of Science, 2012;  NSF American Competitiveness Fellow Award, 2009;  South Carolina Governor's Young Researcher Award for Excellence in Science, 2009;  Camille Dreyfus Teacher-Scholar Award, 2008;  Alfred P. Sloan Foundation Research Fellow, 2008;  The CAPA Distinguished Junior Faculty Award, 2008;  National Science Foundation CAREER Award, 2008.

Research

The research in Wang group is divided into four distinctive but inter-connected topics: (1) chemoselective functionalization of bionanoparticles (BNPs); (2) self-assembly of BNPs towards materials development; (3) cell-recognition study with BNP-assemblies; and (4) fluorogenic reaction for protein imaging and recognition. All these researches point to one direction: to build three-dimensional programmable scaffolds that mimic the native extracellular matrices and can be used to probe the cellular activities.

I. Genetic and chemical modification of selected BNPs
Following the pioneering works of Finn, Johnson and Francis, our group has further explored the surface functionalization of BNPs with genetic and chemical methods. One distinctive feature of our works is that we focus more on the post-functionalization, which has demonstrated simpler but more essential notion of programming functionalities precise to sub-nanometer level. Here are some representative works:

(1) Dual modification of turnip yellow mosaic virus (TYMV) as a prototype BNP for time-resolved fluoroimmuno assay. TYMV is an icosahedral plant virus with an average diameter of 28 nm and can be isolated in grams quantities from turnip or Chinese cabbage inexpensively. Two types of reactive amino acid residues were employed to anchor luminescent terbium complexes and biotin groups based on orthogonal chemical reactions. While terbium complexes were used as luminescent signaling groups, biotin motifs were acted as a model ligand for protein binding (Figure 1). Furthermore, the Cu(l) catalyzed azide-alkyne cycloaddition (CuAAC) reaction, a prototype of "click" chemistry, have been used to post-functionalize TYMV to graft peptide and other ligands to promote or inhibit the cell binding properties.

(2) Chemoselective modification of apoferritin. We reported the chemoselective modification of apoferritin using conventional bioconjugate chemistry, followed with CuAAC reaction and an in situ atom transfer radical polymerization reaction on the outer surface of apoferritin (Figure 2). These transformations afford versatile methods to alter the properties of apoferritin particles, and can be extended to other BNPs.

(3) Extremely efficient conjugation of tobacco mosaic virus (TMV) using CuAAC reaction. TMV is a rod-shaped, 300 nm long and 18 nm in diameter, with a central hold of diameter of 4 nm to encapsidate RNA genome. TMV can be decorated based on the synergistic combination of a CuAAC reaction and an aryldiazonium coupling reaction. The combination of these reactions provides an extremely efficient way (>99.99% transformation for every single step) to conjugate a wide spectrum of compounds to the phenolic groups of tyrosine residues presented on the TMV capsid (Figure 3). To highlight the modularity and efficiency of this "click" conjugation, a cell adhesion assay was performed after TMV was modified with functionalities that can promote or prevent cell adhesion and proliferation.

II. Controlled assembly of BNPs
Our group has systematically investigated the 1D, 2D and 3D assemblies of BNPs. Here are some representative works:

(1) 1D assembly of TMV into nanofibers assisted by in situ polyaniline formation. A head-to-tail ordered assembly of wild type TMV has been discovered, likely a product of complementary hydrophobic interactions between the dipolar ends of the helical structure (Figure 4). Using ammonium persulfate as oxidant, polymerization of aniline took place on the exterior surface of TMV to give a thin layer of polyaniline and afford 1D composite nanofibers as revealed by UV-Vis, AFM, TEM and small angle x-ray scattering (SAXS). The length of composite fiber can be as long as 20 µm, while the diameter of composite was increased by about 1 nm. Unlike other synthetic nanofibers, the TMV-templated polyaniline nanofiber can be readily dispersed in solution or on solid surface by spin coating. In collaboration with Thiyagarajan and Lee (ANL), SAXS and in situ time resolved SAXS on solution samples were performed to measure the growth of polyaniline on the TMV surface and understand the kinetics. In addition, with addition of polyelectrolytes, 1D conducting polyaniline, polypyrrole and other polymeric nanowires can be readily prepared via a similar hierarchical assembly process (Figure 5). Other rod-like viruses, like bacteriophage M13, can also be employed as starting materials.

(2) 2D assembly of BNPs at the interface of immiscible liquids. For the first time, BNPs was successfully self-assembled as a monolayer at the oil-water interfaces and crosslinked with different linkers (Figure 6). These operations did not disrupt the integrity of the virus particles. Furthermore, we recently found that it is possible to generate large areas of well-organized 2D arrays of particles by varying the ionic strength of the aqueous phase (Figure 7).

(3) Raspberry-like colloids assembled from BNPs and polymer. Raspberry-like bionanocomposites can be fabricated via a facile approach using BNPs hybridized with poly(4-vinylpyridine). The size and coverage of the core-shell biocomposites can be controlled by varying the ratio of BNP and poly(4-vinylpyridine) (Figure 8).

III. Cell behavior modulated by BNPs assemblies
We discovered that cell adhesion, spreading, migration, and differentiation can be modulated by the functionalities displayed on BNPs and their assembly patterns. The surface properties of VPs can be used to modulate the cell attachment and proliferation. Moreover, we found that the differentiation of bone mesenchymal stem cells into osteoblasts can be greatly unregulated using plant viruses as substrates. (Figure 9) shows the mineralized osteoblasts after 14 days.

IV. Fluorogenic reactions for bioconjugation and bioimaging We have developed a series of fluorogenic CuAAC reactions based on coumarin, anthracene and BODIPY fluorocores (Figure 10). In addition to being used in the combinatorial synthesis of fluorescent dyes, the most important application of these reactions is the bioconjugation and bioimaging within the intracellular environment. For example, incorporation of exogenous natural or unnatural tags into proteins or glycans by cellular biosynthetic pathways is an emerging strategy for investigating their cellular activities. Since those processes involve multistep enzymatic transformations that prohibit the incorporation of large signaling moieties, chemoselective reactions are often employed for post-labeling. In this case, a bioorthogonal fluorogenic reaction is invaluable, in which the unreacted reagents show no fluorescent background and the purification process can be circumvented. One of the 3-azidocoumarins developed in our group had been successfully utilized for in vivo protein labeling study in collaboration with the D. Tirrell group (CalTech).

Selected Publications

Ren, Y.; Zhang, L.; Sun, T.; Yin, Y.; Wang, Q.; “Enzyme Immobilization on Delignified Bamboo Scaffold as Green Hierarchical Bioreactor”, ACS sustainable chemistry & engineering 2022, 10, 6244-6254, DOI: 10.1021/acssuschemeng.2c00346.

Metavarayuth, K.; Chen, X.; Sitasuwan, P.; Lu, L.; Su, J.; Wang, Q.; “Nanotopographical cues mediate osteogenesis of stem cells on virus substrates through BMP-2 intermediate”, Nano Letters, 2019, 19, 8372-8380, DOI: 10.1021/acs.nanolett.9b02001.

Ratnatilaka Na Bhuket, P.; Luckanagul, J.; Rojsitthisak, P.; Wang, Q.; “Chemical Modification of Enveloped Viruses for Biomedical Applications”, Integrative Biology 2018, 10, 666-679. DOI: 10.1039/C8IB00118A.

Metavarayuth, K.; Sittasuwan, P.; Luckanagul, J. A.; Feng, S.; Wang, Q. " Virus Nanoparticles Mediated Osteogenic Differentiation of Bone Derived Mesenchymal Stem Cells."  Advanced Science 2015, DOI:  10.1002/advs.201500026.

Lin, Y.; Balizan, E.; Lee, L. A.; Niu, Z.; Wang, Q. "Self-Assembly of Rod-Like Bionanoparticles in Capillary Tube." Angew. Chem. Int. Ed. 2010. 49, 868 - 872, DOI: 10.1002/anie.200904993.

Le Droumaguet, C.; Wang, C.; Wang, Q. "Fluorogenic Click Reaction. "Chem. Soc. Rev. 2010. 39, 1233 - 1239, DOI: 10.1039/B901975H.