Principal Investigator, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.

Postdoctoral Fellow, Cell Biology, Harvard Medical School

Ph.D., Biochemistry and Molecular Biology, Peking University

B.S., Basic Medical Sciences, Peking University

Research Summary

The research in Dr. Li’s lab focuses on the transcriptional and epigenetic regulation of gene expression in neurodegenerative diseases and drug-resistant tumors. Genetic, biochemical and bioinformatic methods are integrated to investigate gene misregulation in multiple disease states.

Our current interests range from understanding molecular mechanisms behind gene control to developing novel therapeutic targets for diseases caused by gene dysregulation:

1.      Characterize the novel nuclear function of cytosolic proteins which play key roles in regulating cell death and inflammation.

2.      Discover compounds that regulating nuclear translocation of key factors.

3.      Identify the molecular mechanisms underlying disease-specific mutations of components of chromatin remodeling complex.

Uncover the chromatin remodeling dysregulation and RNA-mediated feedback control in drug-resistant tumors.

Key Publications

https://scholar.google.com/citations?user=VpWN2-gAAAAJ&hl=en&oi=ao

(#equal contribution, *corresponding)

1.      Li, W.*, Shan, B., Zou, C., Wang, H., Zhang, M., Zhu, H., Naito, M. G., Xu, D., Manuel, V. J., Mifflin, L., Ravits, J. & Yuan, J*. Nuclear RIPK1 promotes chromatin remodeling for mediating inflammatory response. Cell Res, doi:10.1038/s41422-022-00673-3 (2022).

2.      Tao, P.#, Sun, J.#, Wu, Z.#, Wang, S.#, Wang, J.#, Li, W.#, Pan, H., Bai, R., Zhang, J., Wang, Y., Lee, P. Y., Ying, W., Zhou, Q., Hou, J., Wang, W., Sun, B., Yang, M., Liu, D., Fang, R., Han, H., Yang, Z., Huang, X., Li, H., Deuitch, N., Zhang, Y., Dissanayake, D., Haude, K., McWalter, K., Roadhouse, C., MacKenzie, J. J., Laxer, R. M., Aksentijevich, I., Yu, X.*, Wang, X.*, Yuan, J.* & Zhou, Q.* A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1. Nature 577, 109-114, doi:10.1038/s41586-019-1830-y (2020).

3.      Li, W., Zhang, Z., Liu, X., Cheng, X., Zhang, Y., Han, X., Zhang, Y., Liu, S., Yang, J., Xu, B., He, L., Sun, L., Liang, J. & Shang, Y*. The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer. J Clin Invest 127, 3421-3440, doi:10.1172/JCI94233 (2017).

4.      Naito, M. G., Xu, D., Amin, P., Lee, J., Wang, H., Li, W., Kelliher, M., Pasparakis, M. & Yuan, J*. Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke. Proc Natl Acad Sci U S A 117, 4959-4970, doi:10.1073/pnas.1916427117 (2020).

5.      Su, Z., Dziedzic, S. A., Hu, D., Barrett, V. J., Broekema, N., Li, W., Qian, L., Jia, N., Ofengeim, D., Najafov, A., Zhu, H., Knipe, D. M. & Yuan, J*. ABIN-1 heterozygosity sensitizes to innate immune response in both RIPK1-dependent and RIPK1-independent manner. Cell Death Differ 26, 1077-1088, doi:10.1038/s41418-018-0215-3 (2019).

6.      Xu, D., Jin, T., Zhu, H., Chen, H., Ofengeim, D., Zou, C., Mifflin, L., Pan, L., Amin, P., Li, W., Shan, B., Naito, M. G., Meng, H., Li, Y., Pan, H., Aron, L., Adiconis, X., Levin, J. Z., Yankner, B. A. & Yuan, J*. TBK1 Suppresses RIPK1-Driven Apoptosis and Inflammation during Development and in Aging. Cell 174, 1477-1491 e1419, doi:10.1016/j.cell.2018.07.041 (2018).

7.      He, L., Liu, X., Yang, J., Li, W., Liu, S., Liu, X., Yang, Z., Ren, J., Wang, Y., Shan, L., Guan, C., Pei, F., Lei, L., Zhang, Y., Yi, X., Yang, X., Liang, J., Liu, R., Sun, L. * & Shang, Y*. Imbalance of the reciprocally inhibitory loop between the ubiquitin-specific protease USP43 and EGFR/PI3K/AKT drives breast carcinogenesis. Cell Res 28, 934-951, doi:10.1038/s41422-018-0079-6 (2018).

8.   Liu, S., Yu, H., Liu, Y., Liu, X., Zhang, Y., Bu, C., Yuan, S., Chen, Z., Xie, G., Li, W., Xu, B., Yang, J., He, L., Jin, T., Xiong, Y., Sun, L., Liu, X., Han, C., Cheng, Z., Liang, J.* & Shang, Y.* Chromodomain Protein CDYL Acts as a Crotonyl-CoA Hydratase to Regulate Histone Crotonylation and Spermatogenesis. Mol Cell 67, 853-866 e855, doi:10.1016/j.molcel.2017.07.011 (2017).

9.   Li, L., Liu, X., He, L., Yang, J., Pei, F., Li, W., Liu, S., Chen, Z., Xie, G., Xu, B., Ting, X., Zhang, Z., Jin, T., Liu, X., Zhang, W., Yuan, S., Yang, Z., Wu, C., Zhang, Y., Yang, X., Yi, X., Liang, J., Shang, Y.* & Sun, L.* ZNF516 suppresses EGFR by targeting the CtBP/LSD1/CoREST complex to chromatin. Nat Commun 8, 691, doi:10.1038/s41467-017-00702-5 (2017).

10.   Zhang, Y., Zhang, D., Li, Q., Liang, J., Sun, L., Yi, X., Chen, Z., Yan, R., Xie, G., Li, W., Liu, S., Xu, B., Li, L., Yang, J., He, L. & Shang, Y*. Nucleation of DNA repair factors by FOXA1 links DNA demethylation to transcriptional pioneering. Nat Genet 48, 1003-1013, doi:10.1038/ng.3635 (2016).