Viral infections pose a serious threat to human health. Using human embryonic stem cells and pluripotent stem cells to differentiate into different tissue cells/organoids to study viral infections can overcome the limitations of traditional cell lines in modeling complex human cells and organ systems. Our group is mainly engaged in research on the mechanism of virus-host interaction. Utilize stem cell differentiation, pathological analysis and drug screening platforms of stem cell derived cells/ organoids to study viral infection and explore potential prevention and treatment strategies for infectious disease.

A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants

Identification of SARS-CoV-2 inhibitors using lung and colonic organoids

Mechanism of host damage caused by viral infection and identification of cytoprotective drugs

Plain English:
Based on the previous background on organoid differentiation and molecular virology, our group will conduct in-depth research on: 1. The impact of genetics and variation on disease progression; 2. Constructing physiological and pathological models of complex organoids; 3. Develop and identify potential drugs for the prevention and treatment of infectious diseases.

Selected publications:

1. Han Y^#, Duan X^#, Yang L^#, Nilsson-Payant BE^#, Wang P^#, Duan F^#, Tang X^#, Yaron TM^#, Zhang T, Uhl S, Bram Y, Richardson C, Zhu J, Zhao Z, Redmond D, Houghton S, Nguyen DT, Xu D, Wang X, Jessurun J, Borczuk A, Huang Y, Johnson JL, Liu Y, Xiang J, Wang H^#, Cantley LC^*, tenOever BR^*, Ho DD^*, Pan FC^*, Evans T^*, Chen HJ^*, Schwartz RE^* and Chen S^*. Identification of SARS-CoV-2 inhibitors using lung and colonic organoids. Nature. 2021; 589: 270-275
2. Wang X^#, Xuan Y^#, Han Y^#, Ding X, Ye K, Yang F, Gao P, Goff SP and Gao G^*. Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting. Cell. 2019; 176:625-635 e14.
3. Han Y^#, Tan L^#, Zhou T^#, Yang L^#, Carrau L^#, Lacko LA, Saeed M, Zhu J, Zhao Z, Nilsson-Payant BE, Lira Neto FT, Cahir C, Giani AM, Chai JC, Li Y, Dong X, Moroziewicz D, Team NGSCA, Paull D, Zhang T, Koo S, Tan C, Danziger R, Ba Q, Feng L, Chen Z, Zhong A, Wise GJ, Xiang JZ, Wang H, Schwartz RE, tenOever BR, Noggle SA, Rice CM, Qi Q, Evans T and Chen S^*. A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants. Cell Stem Cell. 2022; 29:1475-1490 e6.
4. Yang L^#, Han Y^#, Nilsson-Payant BE^#, Gupta V^#, Wang P, Duan X, Tang X, Zhu J, Zhao Z, Jaffre F, Zhang T, Kim TW, Harschnitz O, Redmond D, Houghton S, Liu C, Naji A, Ciceri G, Guttikonda S, Bram Y, Nguyen DT, Cioffi M, Chandar V, Hoagland DA, Huang Y, Xiang J, Wang H, Lyden D, Borczuk A, Chen HJ, Studer L, Pan FC^*, Ho DD^*, tenOever BR^*, Evans T^*, Schwartz RE^* and Chen S^*. A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids. Cell Stem Cell. 2020; 27:125-136 e7. Best of Cell Stem Cell 2020.
5. Han Y^#, Zhu J^#, Yang L^#, Nilsson-Payant BE^#, Hurtado R, Lacko L, Sun X, Gade AR, Higgins CA, Sisso WJ, Dong X, Wang M, Zhengming Chen, Ho DD, Pitt GS, Schwartz RE^*, tenOever BR^*, Evans T^* and Chen S^*. SARS-CoV-2 infection Induces Ferroptosis of Sinoatrial Node-like Pacemaker Cells. Circ Res. 2022 130:963-977. Circulation Research Best Manuscript 2022.
6. Han Y^#, Yang L^#, Lacko L and Chen S^*. Human Organoid Models to Study SARS-CoV-2 Infection. Perspective, Nature Methods. 2022 4:418-428.
7. Yang L^#, Han Y^#, Jaffre F^#, Nilsson-Payant BE^#, Bram Y^#, Wang P, Zhu J, Zhang T, Redmond D, Houghton S, Uhl S, Borczuk A, Huang Y, Richardson C, Chandar V, Acklin JA, Lim JK, Chen Z, Xiang J, Ho DD, tenOever BR^*, Schwartz RE^*, Evans T^* and Chen S^*. An Immuno-Cardiac Model for Macrophage-Mediated Inflammation in COVID-19 Hearts. Circ Res. 2021 129:33-46. Cover story
8. Yang L^#, Kim TW^#, Han Y^#, Nair MS^#, Harschnitz O^#, Zhu J^#, Wang P^#, Koo SY, Lacko LA, Chandar V, Bram Y, Zhang T, Zhang W, He F, Pan C, Wu J, Huang Y, Evans T, van der Valk P, Titulaer MJ, Spoor JKH, Furler O'Brien RL, Bugiani M, W DJVdB, Schwartz RE^*, Ho DD^*, Studer L^* and Chen S^*. SARS-CoV-2 infection causes dopaminergic neuron senescence. Cell Stem Cell. 2024.
9. Yang L^#, Nilsson-Payant BE^#, Han Y^#, Jaffré F^#, Zhu J^#, Wang P, Zhang T, Redmond D, Houghton S and Møller R, Hoagland D, Carrau L, Horiuchi S, Goff M, Lim JK, Bram Y, Richardson C, Chandar V, Borczuk A, Huang Y, Xiang J, Ho DD^*, Schwartz RE^*, tenOever BR, Evans T^* and Chen S^*. Cardiomyocytes Recruit Monocytes upon SARS-CoV-2 Infection by Secreting CCL2. Stem Cell Reports. 2021 Jul 20.
10. Yang L^#, Han Y^#, Zhou T^#, Lacko LA, Saeed M, Tan C, Danziger R, Zhu J, Zhao Z, Cahir C, Giani AM, Li Y, Dong X, Moroziewicz D, Team NGSCA, Paull D, Chen Z, Zhong A, Noggle SA, Rice CM, Qi Q, Evans T and Chen S^*. Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection. iScience. 2023;26:107001.