Signaling pathways controlling normal cell growth are almost invariably altered in cancer. Studies in past decades have established multiple evolutionarily conserved signaling cascades, such as Wnt, TGF-b, and Hippo. My Ph.D. work was mainly focused on the molecular mechanisms of Wnt/β-catenin signaling and its role in development and tumorigenesis. Using a comprehensive approach that combines bioinformatics, molecular cell, developmental, and cancer biology, we have found that a previously poor-characterized protein Twa1 is a key nuclear retention factor for β-catenin in Wnt signaling and plays important roles in dorsoventral patterning of zebrafish embryo and colorectal tumorigenesis.
Currently, I focus on another two important signaling pathways, the TGF-β pathway and Hippo pathway, which also participate in tissue development and homeostasis. SnoN and the related Ski protein, which negatively regulate TGF-β signaling by binding to the Smad proteins, are recently found as an important regulator of Hippo signaling. In addition, SnoN can also activate the p53 pathway in response to various cellular stress signals. I am interested in understanding the functions of SnoN and Ski and how they coordinate the actions of these signaling pathways in various aspects of development and in tumorigenesis using a combination of in vitro culture cell lines, three-dimentional culture models and in vivo mouse models.
Impact in China
Signaling cascades play pivotal roles in cell proliferation, cell fate determination, and stem cell maintenance. Dysfunction of these pathways is often implicated in a variety of human diseases, most prominent in cancer. Cancer is currently the leading cause of death in China. My scientific and technological training at UC Berkeley will enable me to explore the molecular mechanism of signaling pathways and how alteration of these signaling cascades contributes to tumorigenesis, which could provide new insights and targets for cancer diagnosis and therapy.
Yi Lu*, Shanshan Xie*, Wen Zhang*, Cheng Zhang, Cheng Gao, Yuqi Cai, Qiang Sun, Zhangqi Xu, Min Xiao, Yanjun Xu, Xiao Huang, Wei Liu, Fudi Wang, Yibin Kang, Tianhua Zhou. (2017) Twa1/Gid8 is a β-catenin nuclear retention factor in Wnt signaling and colorectal tumorigenesis. Cell Research 27:1422-1440.
Cheng Zhang*, Wen Zhang*, Yi Lu*, Xiaoyi Yan, Xiumin Yan, Xueliang Zhu, Wei Liu, Yuehong Yang, Tianhua Zhou. (2015) NudC regulates actin dynamics and ciliogenesis by stabilizing cofilin 1. Cell Research 26:239-253.
Sijie Feng*, Yinlong Song*, Minhong Shen*, Shanshan Xie*, Wenjing Li, Yi Lu, Yuehong Yang, Guangshuo Ou, Jun Zhou, Fudi Wang, Wei Liu, Xiaoyi Yan, Xin Liang, Tianhua Zhou. (2017) Microtubule-binding protein FOR20 promotes microtubule depolymerization and cell migration. Cell Discovery 3:17032.