FLORIDA STATE / PEOPLE / FACULTY
Dr. Hengli Tang, Professor
Ph.D., University of California, San Diego, 1998
The general area of research interest in my lab is virus-host cell interactions concerning hepatitis C virus (HCV) and flaviviruses such as dengue (DENV) and Zika viruses (ZIKV). We are currently using pluripotent stem cells and targeted differentiation in vitro to study viral susceptibility of cells from distinct lineages.
1. Stem cell differentiation and positive-strand RNA viruses
Pluripotent stem cells can be differentiated into all cell lineages in vitro, providing distinct cell types with identifical genetic background for studies of virus susceptiblity. In addition, the tightly controlled nature of the in vitro differentiation steps is also well-suited for identifying the transition to virus permissiveness during differentiation. We have previously published hepatic differentiation and HCV infection (Wu et al. PLoS Pathogens 2012) and are currently using additional differentiated cells for the studies of dengue virus and Zika virus.
Recent papers on Zika virus:
Recent papers on Dengue virus:
2. Cellular cofactors of viral infection
My lab has characterized two cellular cofactors essential for HCV infection. We investigated in depth the relationship between Cyclophilin A (CyPA), a host factor, and HCV infection in vitro. HCV infection of cultured hepatoma cells or differentiated hepatocyte-like cells derived from stem cells is critically dependent on CyPA but not several other isoforms of CyPs. The peptidylprolyl isomerase (PPIase) motif of CyPA is essential for the function of the HCV replicase. In vitro resistance to CsA, albeit modest, is directly correlated with a reduced dependence on CyPA; and a functional interaction between CyPA and the HCV replicase exists. NS5A, a HCV non-structural protein and a component of the viral replicase, is an important target of CyPA. Mutations that alter NS5A conformation reduce HCV’s dependence on CyPA. The second cellular cofactor, CIDEB, is not only important for HCV infection but may also play a role in HCV-mediated lipid dysregulation.
3. Cofactor-Independent Mutants (CoFIM) selection
A myriad of cellular cofactors have been identified by various labs using shot-gun style technologies such as siRNA screening (genome-wide or targeted) and cDNA expression cloning. However, the mechanisms of action for many of these factors remain unknown. We have devised a Cofactor-Independent Mutants (CoFIM) identification technique (Yang et al. PLoS Pathogens, 2010) to select for mutations that confer the ability to a mutant virus that can infect cells where the expression of a specific cofactor is suppressed by stable shRNA. This approach allows us to identify the viral targets and the mutations relevant for the function of given cofactors. We have validated this technology with CyPA, an essential cofactor of HCV that has been well characterized by us and others. We are now applying the CoFIM technique to additional HCV and HIV cofactors.
|Lang J, Cheng Y, Rolfe A, Hammack C, Vera D, Kyle K, Wang J, Meissner TB, Ren Y, Cowan C, Tang H. An hPSC-Derived Tissue-Resident Macrophage Model Reveals Differential Responses of Macrophages to ZIKV and DENV Infection. Stem Cell Reports. 2018 Aug 14;11(2):348-362. doi: 10.1016/j.stemcr.2018.06.006. Epub 2018 Jul 5.|
|Yang S, Xu M, Lee EM, Gorshkov K, Shiryaev SA, He S, Sun W, Cheng YS, Hu X, Tharappel AM, Lu B, Pinto A, Farhy C, Huang CT, Zhang Z, Zhu W, Wu Y, Zhou Y, Song G, Zhu H, Shamim K, Martínez-Romero C, García-Sastre A, Preston RA, Jayaweera DT, Huang R, Huang W, Xia M, Simeonov A, Ming G, Qiu X, Terskikh AV, Tang H, Song H, Zheng W. Emetine inhibits Zika and Ebola virus infections through two molecular mechanisms: inhibiting viral replication and decreasing viral entry. Cell Discov. 2018 Jun 5;4:31. doi: 10.1038/s41421-018-0034-1. eCollection 2018.|
|Song G, Rho HS, Pan J, Ramos P, Yoon KJ, Medina FA, Lee EM, Eichinger D, Ming GL, Muñoz-Jordan JL, Tang H, Pino I, Song H, Qian J, Zhu H. Multiplexed Biomarker Panels Discriminate Zika and Dengue Virus Infection in Humans. Mol Cell Proteomics. 2018 Feb;17(2):349-356. doi: 10.1074/mcp.RA117.000310. Epub 2017 Nov 15.|
|Ming GL, Song H, Tang H. Racing to Uncover the Link between Zika Virus and Microcephaly. Cell Stem Cell. 2017 Jun 1;20(6):749-753. doi: 10.1016/j.stem.2017.05.010|
|Yoon, K., Song G., Qian X., Pan J., Xu D., Rho H., Kim N., Habela C., Zheng L., Jacob Fadi., Zhang F., Lee EM., Huang W., Ringeling FR., Vissers C., Li C., Yuan L., Kang K., Kim S., Yeo J., Cheng Y., Liu S., Wen Z., Qin C., Christian KM., Hengli T., Jin P., Xu Z., Qian J., Zhu H., Song H., Ming G. 2017 Jul 14.;Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins. Cell Stem Cell.|
|Oh Y., Zhang F., Wang Y., Lee EM., Choi IY., Lim H., Mirakhori F., Li R., Huang L., Xu T., Wu H., Li C., Qin C., Wen Z., Wu Q., Tang H., Xu Z., Jin P., Song H., Ming G., Lee G. 2017 Jul 31.;Zika virus directly infects peripheral neurons and induces cell death. Nature Neuroscience. –|
|Ming, Guo-li, Tang, Hengli and Song, Hongjun 2016 Dec 1. Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities Cell Stem Cell 19:690-702|
|Xu, M., Lee, EM.,Wen, Z., Cheng, Y., Huang, W., Qian, X., TCW, J., Kouznetsova, J., Ogden., SC., Hammack, C., Jacob, F., Nguyen, HN., Itkin, M., Hanna, C., Shinn, P., Allen, C., Michael, SG., Simeonov, A., Huang, W., Christian, KM., Goate, A., Brennand, KJ., Huang, R., Xia, M., Ming, G., Zheng, W., Song, H., Tang, H. 2016 Aug 22. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nature Medicine. doi:10.1038/nm.4184|
|Zhang, F., Hammack, C., Ogden, S. C., Cheng, Y., Lee, E. M., Wen, Z., Qian, X., Nguyen, H., Li ,Y., Yao, B., Xu, M., Xu, T., Chen, L., Wang, Z., Feng, H., Huang, W., Yoon, K., Shan, C., Huang, L., Qin, Z., Christian, K M., Shi, P., Xu, M., Xia, M., Zheng, W., Wu, H., Song, H., Tang, H., Ming, G., Jin, P. 2016 Aug 31. Molecular signatures associated with ZIKV exposure in human cortical neural progenitors. Nucleic Acids Research, doi:10.1093/nar/gkw765|
|Zhan, N.; Palui, G.; Grise, H.; Tang, H.; Alabugin, I.; Mattoussi, H. Combining ligand design with photo-ligation to provide compact, colloidally stable and easy to conjugate quantum dots. ACS Applied Materials & Interfaces (invited). 2013, 5, 2861-2869. http://pubs.acs.org/doi/abs/10.1021/am302788q.|
|Lang, J., Vera, D., Cheng, Y., & Tang, H. 2016 Aug 16. Modeling dengue virus-hepatic cell interactions using human pluripotent stem cell-derived hepatocyte-like cells. Stem Cell Reports, doi:http://dx.doi.org/10.1016/j.stemcr.2016.07.012|
|Qian, X., Ha Nam Nguyen, Song, M. M., Hadiono, C., Ogden, S. C., Hammack, C., Yao, B., Hamersky, GR., Jacob, F., Zhong, C., Yoon, KJ., Jeang, W., Lin, L., Li, YJ., Thakor, J., Berg, DA., Zhang, C., Kang, E., Chickering, M., Nauen, D., Ho, CY., Wen, ZX., Christian, KM., Shi, PY., Maher, BJ., Wu, H., Jin, P., Tang, HL., Song, HJ., Ming, G. 2016 May 19. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell, 165(5), 1238-1254. doi:10.1016/j.cell.2016.04.032|
|Tang H, Hammack C, Ogden SC, Wen Z, Qian X, Li Y, Yao B, Shin J, Zhang F, Lee EM, Christian KM, Didier RA, Jin P, Song H, Ming GL. Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth. Cell Stem Cell. 2016 Mar 3. pii: S1934-5909(16)00106-5. doi: 10.1016/j.stem.2016.02.016. [Epub ahead of print]|
|Gold, B.; Dudley, G. B.; Alabugin, I. V. Moderating strain without sacrificing reactivity: Design of fast and tunable non-catalyzed alkyne-azide cycloadditions via stereoelectronically controlled transition state stabilization. J. Amer. Chem. Soc., 2013, 135, 1558-1569. http://pubs.acs.org/doi/abs/10.1021/ja3114196.|
|Lee EM, Alsagheir A, Wu X, Hammack C, McLauchlan J, Watanabe N, Wakita T, Kneteman NM, Douglas DN, Tang H. Hepatitis C virus induced degradation of cell death-inducing DFFA-like effector B leads to hepatic lipid dysregulation. J Virol. 2016 Feb 10. pii: JVI.02891-15. [Epub ahead of print]|
|Hookway TA, Butts JC, Lee E, Tang H, McDevitt TC. Aggregate formation and suspension culture of human pluripotent stem cells and differentiated progeny. Methods. 2015 Dec 2. pii: S1046-2023(15)30167-5. doi: 10.1016/j.ymeth.2015.11.027. [Epub ahead of print]|
|Ogden SC, Tang H. The missing pieces of the HCV entry puzzle. Future Virol. 2015;10(4):415-428.|