YU Qiang

 

RESEARCH

Dr. Qiang Yu's research at the Genome Institute of Singapore focuses on uncovering mechanisms of cancer progression, immune evasion, and therapeutic resistance. They integrate genomics, epigenetics, and immunology to develop precision cancer therapies. Dr. Yu's lab was the first to discover DZNep as a histone methylation inhibitor, a breakthrough in targeting epigenetic regulators in cancer. This work provided foundational insights into inhibiting EZH2, a key component of the Polycomb repressive complex 2 (PRC2), leading to new therapeutic strategies for epigenetically driven cancers. The team also uncovered the non-catalytic function of EZH2, demonstrating its role in promoting tumor growth independently of its histone methyltransferase activity. Additionally, they explore genomic biomarkers and targeted therapies, identifying chromosome 1q21.3 amplification as a trackable biomarker and therapeutic target for breast cancer recurrence, along with novel oncogenic signaling pathways. These findings are being translated into clinical applications.

A significant recent focus of the team is the tumor microenvironment, particularly in understanding the immune suppressive tumor microenvironment of solid tumors. They have shown how cancer-associated fibroblasts (CAFs) contribute to therapy resistance in colorectal cancer. The team has also identified EZH2-mediated immune deficiency as a key mechanism leading to anti-HER2 immunotherapy and hypoxia-driven epigenetic reprogramming of T cell effector activity in breast cancer.

Their latest work revealed P4HA1 as a critical regulator of CD8+ T cell differentiation, with targeting P4HA1 promoting the expansion of T cell progenitors toward an immune memory phenotype, enhancing systemic anti-tumor immunity. This discovery has significant implications for improving T cell-based immunotherapies and overcoming immune exhaustion in cancer. Based on this finding, they are developing novel T cell technology platforms to empower T cell therapy, such as CAR T cell therapy for solid tumors. Through these discoveries, Dr. Yu's team is pioneering new approaches to precision medicine, epigenetic therapy, and immune-based cancer treatments, bridging fundamental cancer biology with translational applications.

Selected Publications

• Ma S, Ong LT, Jiang Z, Lee WC, Lee PL, Yusuf M, Ditzel HJ, Wang Y, Chen Q, Wang W, Wu X, Tan EY, Yu Qiang. Targeting P4HA1 promotes CD8(+) T cell progenitor expansion toward immune memory and systemic anti-tumor immunity. Cancer Cell. 2024 Dec 23:S1535-6108(24)00476-8. doi: 10.1016/j.ccell.2024.12.001. Online ahead of print.PMID: 39729997
• Jian Yuan Goh, Min Feng, Wenyu Wang, Gokce Oguz, Siti Maryam J M Yatim, Puay Leng Lee, Yi Bao, Tse Hui Lim, Panpan Wang, Wai Leong Tam, Annette R Kodahl, Maria B Lyng, Suman Sarma, Selena Y Lin, Alexander Lezhava, Yoon Sim Yap, Alvin S T Lim, Dave S B Hoon, Henrik J Ditzel, Soo Chin Lee, Ern Yu Tan, Qiang Yu. Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence. Nature Medicine 2017 23, 1319–1330.
• Tan J, Li Z, Lee PL, Guan P, Aau M, Lee ST, Feng M, Lim CZ, Lee EY, Wee ZN, Lim YC, Karuturi RK, Qiang Yu. "PDK1 Signaling Towards PLK1-Myc Activation Confers Oncogenic Transformation and Tumor Initiating Cell Activation and Resistance to mTOR-targeted Therapy." Cancer Discovery 2013 Oct;3(10):1156-71.
• Jing Tan, Puay Leng Lee, Zhimei Li, Xia Jiang, Yaw Chyn Lim, Shing Chuan Hooi, and Qiang Yu. B55β-associated PP2A complex controls PDK1-directed Myc signaling and modulates rapamycin sensitivity in colorectal cancer. Cancer Cell 2010 18:459-471.
• Xia Jiang, Jing Tan, Jingsong Li, Saul Kivimäe, Xiaojing Yang, Li Zhuang, Puay Leng Lee, Mark TW. Chan, Lawrence Stanton, Edison T. Liu, Benjamin N.R.Cheyette, and Qiang Yu. DACT3 is an epigenetic regulator of Wnt/β-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications. Cancer Cell. 2008 13:529.
• Shuet Theng Lee, Zhimei Li, Zhenlong Wu, Meiyee Aau, Peiyong Guan, R.K. Murthy Karuturi, Yih Cherng Liou, and Qiang Yu. "Context-Specific Regulation of NF-kB Target Gene Expression by EZH2 in Breast Cancers". Molecular Cell 2011, 43, 798–810.
• Shijun Ma, Yue Zhao, Wee Chyan Lee, Li-Teng Ong, Puay Leng Lee, Zemin Jiang, Gokce Oguz, Zhitong Niu, Min Liu, Jian Yuan Goh, Wenyu Wang, Matias A Bustos, Sidse Ehmsen, Adaikalavan Ramasamy, Dave S B Hoon, Henrik J Ditzel, Ern Yu Tan, Qingfeng Chen and Qiang Yu. Hypoxia induces HIF1α-dependent epigenetic vulnerability in TNBC to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy. Nature Comm, 2022, 13: 4118
• Li-Teng Ong, Wee Chyan Lee, Shijun Ma, Gokce Oguz, Zhitong Niu, Yi Bao, Mubaraka Yusuf, Puay Leng Lee, Jian Yuan Goh, Panpan Wang, Kylie Su Mei Yong, Qingfeng Chen, Wenyu Wang, Adaikalavan Ramasamy, Dave S. B. Hoon, Henrik J Ditzel, Ern Yu Tan, Soo Chin Lee, and Qiang Yu. IFI16-dependent STING signaling is a crucial regulator of anti-HER2 immune response in breast cancer. Proc Natl Acad Sci U S A 2022 Aug 2;119(31):e2201376119.
• Wei CL, Wu Q, Vega VB, Chiu KP, Ng P, Zhang T, Shahab A, Yong HC, Fu Y, Weng Z, Liu J, Zhao XD, Chew JL, Lee YL, Kuznetsov VA, Sung WK, Miller LD, Lim B, Liu ET, Yu Q, Ng HH, Ruan Y. A global map of p53 transcription-factor binding sites in the human genome. Cell. 2006, 124(1):207-19.
• Jing Tan, Xiaojing Yang, Li Zhuang, Xia Jiang, Wei Chen, Puay Leng Lee, RK Murthy Karuturi, Patrick Boon Ooi Tan, Edison T. Liu and Qiang Yu. Pharmacologic disruption of Polycomb repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes & Development 2007 21:1050. PMID: 17437993 .