Research Interests
My laboratory’s research focuses on elucidating the mechanisms of cancer progression and immunotherapy resistance.
Project 1. Mechanistic study and therapeutic strategy development of CRPC
Castration-Resistant Prostate Cancer (CRPC) is the major cause of death for prostate cancer patients. Mechanistic studies of invasive/metastatic CRPC are key for facilitating the discovery of more effective treatments. My previous studies elucidated the essential roles of PI3K p110β isoform in CRPC tumorigenesis based on both in vitro and in vivo tumor models. This investigation illuminates rationally designed novel therapeutic strategies for invasive CRPC, which could potentially benefit prostate cancer patients with minimal side effects since p110β activity is not essential to most normal physiology. The current study aims to elucidate the molecular mechanisms involved in metastatic CRPC. The long-term objective of my research is to understand the molecular mechanisms that govern CRPC progression and devise new treatments for metastatic CRPC.
- Haizhen Wang, Yu Zhou, Chen Chu, Jialing Xiao, Shanshan Zheng, Manav Korpal, Joshua M. Korn, Tiffany Penaloza, Richard R. Drake, Wenjian Gan, Xueliang Gao#. Generating a mouse PTEN null prostate cell line to discover the key role of p110β-PAK1 in CRPC migration. Molecular Cancer Research 2023.
- Xueliang Gao#, *, Yubao Wang*, Caroline F. Ribeiro*, Cherubin Manokaran, Hyeyoun Chang, Thanh Von, Silvia Rodrigues, Onur Cizmecioglu, Shidong Jia, Manav Korpal, Joshua M. Korn, Zhigang Wang, Fabienne Schmit, Lan Jiang, Raymond Pagliarini, Yi Yang, Isha Sethi, Sabina Signoretti, Guo-Cheng Yuan, Massimo Loda#, Jean J. Zhao#, Thomas M. Roberts# Blocking PI3K p110β Attenuates Development of PTEN-Deficient Castration-Resistant Prostate Cancer. Molecular Cancer Research 2022.
- Jing Zhang, Xueliang Gao, Fabienne Schmit, Guillaume Adelmant, Michael J. Eck, Jarrod A. Marto, Jean J. Zhao, and Thomas M. Roberts CRKL mediates p110β-dependent PI3K signaling in PTEN-deficient cancer cells Cell Reports 2017.
- Shidong Jia*, Xueliang Gao*, Sang Hyun Lee, Sauveur-Michel Maira, Xiaoqiu Wu, Edward Stack, Sabina Signoretti, Massimo Loda, Jean J Zhao & Thomas M. Roberts. Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention. Cancer Discovery 2013.
- Manav Korpal, Joshua M. Korn*, Xueliang Gao*, Daniel P. Rakiec, David A. Ruddy, Shivang Doshi, Jing Yuan, Steve Kovats, Sunkyu Kim, Vesselina G. Cooke, John Monahan, Frank Stegmeiera, Thomas M. Roberts, William R. Sellers, Wenlai Zhou, Ping Zhu. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discovery 2013.
Project 2. Cyclin-dependent Kinase (CDK) functions in immunotherapy resistance
Our study showed that CDK6 depletion reshapes the tumor immune microenvironment,. This occurs by CDK6 phosphorylating and increasing the activities of PTP1B and TCPTP, which in turn decreases tyrosine phosphorylation of CD3ζ, thus reducing the signal transduction for T-cell activation. Administration of a PTP1B and TCPTP inhibitor proved efficacious in enhancing T-cell mediated immunotherapy. Our study demonstrated that targeting PTPs might be effective for cancer patients who resist immunotherapy treatment. We will continue to determine the unknown but critical function of CDKs in regulating the efficacy of immune checkpoint blockade.
- Xueliang Gao#, *, Yongxia Wu*, Joel M. Chick, Andrea Abbott, Baishan Jiang, David J. Wang, Susana Comte-Walters, Roger H. Johnson, Nathaniel Oberholtzer, Michael I. Nishimura, Steven P. Gygi, Anand Mehta, Denis C. Guttridge, Lauren Ball, Shikhar Mehrotra, Piotr Sicinski, Xue-Zhong Yu, Haizhen Wang#. Targeting protein tyrosine phosphatases for CDK6 induced immunotherapy resistance. Cell Reports 2023.
- Xueliang Gao*, Shenhui Qin*, Yongxia Wu, Chen Chu, Baishan Jiang, Roger H. Johnson, Dong Kuang, Jie Zhang, Xi Wang, Anand Mehta, Kenneth D Tew, Gustavo W Leone, Xue-Zhong Yu and Haizhen Wang#. Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia. The Journal of Clinical Investigation 2021.
- Wenjun Xiong*, Xueliang Gao*, Tiantian Zhang, Baishan Jiang, Mingming Hu, Xia Bu, Yang Gao, Lin-Zhou Zhang, Bo-Lin Xiao, Chuan He, Yishuang Sun, Haiou Li, Jie Shi, Xiangling Xiao, Bolin Xiang, Conghua Xie, Gang Chen, Haojian Zhang, Wenyi Wei, Gordon J. Freeman, Hong-Bing Shu, Haizhen Wang, and Jinfang Zhang. USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy. Nature Communications 2022.
- Haizhen Wang#, Tiffany Penaloza, Amanda Menea, Xueliang Gao#. PFKP: More Than Phosphofructokinase. Advances in Cancer Research 2023.
- Janisha Patel, Xueliang Gao, Haizhen Wang#. An update on clinical trials and potential therapeutic strategies in T-cell Acute Lymphoblastic Leukemia. International Journal of Molecular Sciences 2023.
- Xueliang Gao, Gustavo W. Leone and Haizhen Wang Cyclin Ds-CDK4/6 functions in cancer. Advances in Cancer Research 2020.
Other Selected Publications
- Xueliang Gao*, Haizhen Wang*, Jenny J. Yang, Xiaowei Liu, and Zhi-Ren Liu. Pyruvate Kinase M2 Regulates Gene Transcription by Acting as a Protein Kinase. Molecular Cell 2012.
- Xueliang Gao*, Haizhen Wang*, Jenny, J. Yang, Jing Chen, Jiang Jie, Liangwei Li, Yinwei Zhang, and Zhi-Ren Liu. Reciprocal Regulation of Protein Kinase and Pyruvate Kinase Activities of Pyruvate Kinase M2 by Growth Signals. Journal of Biological Chemistry 2013.
- Xueliang Gao*, #, Haizhen Wang, Jenny Yang and Zhi-Ren Liu*. Prevent protein interactions to prevent cancer metastasis. Expert Review of Proteomics 2013.
Note: *contribute equally, # co-corresponding authors
