Willis X. Li
Professor of Medicine
Ph.D., Columbia University
My lab studies the JAK/STAT signaling pathway, which plays important roles in animal development, cancer, and immune responses. Our research has elucidated a non-canonical mode of JAK/STAT signaling, in which a fraction of the unphosphorylated form of STAT is associated with heterochromatin and is important for maintaining heterochromatin stability. We have further shown that human STAT5A, in its unphosphorylated form, also promotes heterochromatin formation and functions as a tumor suppressor. Our current research is focused on elucidating the molecular mechanism by which the non-canonical JAK/STAT pathway and heterochromatin dynamics epigenetically regulate cellular processes important for cancer development or tumor suppression.
BMS Focus Areas:
Lim, S.J., Scott, A., Xiong, X.P., Vahidpour, S., Karijolich, J., Guo, D., Pei, S., Yu, Y.-T., Zhou, R., Li, W.X. (2014) Requirement for CRIF1 in RNA interference and Dicer-2 stability. RNA Biol., in press.
Tsurumi, A., Dutta, P., Yan, SJ., Sheng, R, Li, W.X. (2013) Drosophila Kdm4 demethylases in histone H3 lysine 9 demethylation and ecdysteroid signaling. Sci. Rep. 2013 Oct 8;3:2894. PMC3792421
Hu, X., Dutta, P., Tsurumi, A., Li, J., Wang, J., Land, H., and Li, W.X. Unphosphorylated STAT5A stabilizes heterochromatin and suppresses tumor growth. Proc. Natl. Acad. Sci. USA. 110(25):10213-8 [Epub 2013 Jun 3] PMC3690839.
Gaur, K., Li, J., Wang, D., Dutta, P., Yan, SJ., Tsurumi, A., Land, H., Wu, G., and Li, W.X. The Birt-Hogg-Dube tumor suppressor Folliculin negatively regulates ribosomal RNA synthesis. Hum Mol Genet. 2013 Jan 15;22(2):284-99.
Larson, K., Yan, S.-J.,Tsurumi, A., Liu, J., Zhou,J., Gaur,K., Guo, D., Eickbush, T.H., and Li, W.X. (2012) Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genetics 8(1):e1002473. [Epub 2012 Jan 26]
Tsurumi, A., Xia, F., Li, J., Larson, K., LaFrance, R., and LI, W.X. (2011) STAT is an essential activator of the zygotic genome in the early Drosophila embryo. PLoS Genetics 7(5): e1002086.
Yan, S.-J., Lim, S.J., Shi, S., Dutta, P., and Li, W.X. (2011) Unphosphorylated STAT and heterochromatin protect genome stability. FASEB Journal. 25(1):232-41. [Epub ahead of print Sep 16, 2010]
Yan, S.-J., Zartman, J.J., Zhang, M., Scott, A., Shvartsman, S. Y., and Li, W.X. (2009) Bistability coordinates the activation of the EGFR and Dpp pathways in Drosophila wing vein differentiation. Molecular Systems Biology 5:278. Epub 2009 Jun 16
Li, W.X. (2008) Canonical and noncanonical JAK/STAT signaling. Trends in Cell Biology. 18, 545-51. Epub 2008 Oct 9. (review).
Xia, F., Li, J., Hickey, G.W., Tsurumi, A., Larson, K., Guo, D, Yan, S.-J., Silver-Morse, L, and Li, W.X. (2008) Drosophila Raf activation is regulated by tyrosine 510 phosphorylation. PLoS Biology 6(5): e128.
Shi, S., Larson, K., Guo, D., Dutta, P., Lim, S., Yan, S.-J., and Li, W.X. (2008) Drosophila STAT is directly required for maintaining HP1 localization and heterochromatin stability. Nature Cell Biology 10, 489-96; Epub 2008 Mar 16.
Xing, Y., Shi, S., Le, L., Lee, C. A., Silver-Morse, L., and Li, W.X. (2007) Evidence for transgenerational transmission of epigenetic tumor susceptibility in Drosophila. PLoS Genetics 3(9):e151; 1598-606. Epub 2007 Jul 20. (Editor’s Pick of the Week).
Li, J., and Li, W.X. (2006) A novel function of Drosophila eIF4A as a negative regulator of Dpp/BMP signalling that mediates SMAD degradation. Nature Cell Biology 8, 1407-14; Epub 2006 Nov 19. (Commented in News and Views)
Mogila, V., Xia, F., and Li, W.X. (2006) An intrinsic cell-cycle checkpoint pathway mediated by MEK and ERK in Drosophila. Developmental Cell 11, 575-582. (Commented in In This Issue)
Shi, S., Calhaun, H.C., Xia, F., Li, J., Le, L., and Li, W.X. (2006) JAK signaling globally counteracts heterochromatic gene silencing. Nature Genetics 38, 1071-6. Epub 2006 Aug 6. (Commented in News and Views)
Li, J., Xia, F., and Li, W.X. (2003) Coactivation of STAT and Ras is required for germ cell proliferation and invasive migration in Drosophila. Developmental Cell, 5, 787-798.