RESEARCH
We are looking for postdocs (fresh graduates) and research assistants in 2018. Candidates with excellent track record in cancer biology and expertise in mouse experiments are encouraged to apply .
Our research is focused on questions related to cancer therapeutics. Cancer is a complex disease and the malignant phenotype involves extensively rewired pathways for growth advantage and survival due to multiple genetic and epigenetic changes. The complexity of alterations in cancer presents a daunting problem with respect to treatment: the malignant process involves multiple aberrant compensatory signaling routes that bypass the inhibition of individual. In addition, cancer is a genetic moving target capable of mutating into resistant or more aggressive forms. Thus, a key to successful therapy is to identify the critical nodes in the oncogeneic network and to target them to reverse cancer phenotypes by inducing apoptosis, senescence and differentiation. In order to generate this system failure in cancer, the most effective approach is probably through the combinational application of a relatively small number of drugs through system perturbation.
We are leveraging various technologies to understand the fundamental questions concerning cancer cell death and survival. Integrating functional genomics, chemical combinations and molecular biology, we are exploring systems biology approach to identify key elements that are critical to a relevant biological phenotype, to identify synthetic lethal gene-gene interactions and to develop novel strategies for cancer therapy.
Damage Response, Cell Cycle Checkpoint and Apoptosis:The majority of therapeutic agents cause DNA damage response, leading to activation of cell cycle checkpoint or apoptosis. Understanding the signals and mechanisms leading to apoptosis or resistance to apoptosis may allow the development of better regimens for the treatment of cancer. Using both genomics mapping and chemical screening approaches, as well as in collaboration with our technology group, we are interested in identifying the key gene modules that are associated with anticancer drug response and deciphering molecular mechanisms of activity of their products as potential targets for therapeutic modulation (J Bio Chem., 2004, Cancer Res. 2005, Cell, 2006, Cancer Res. 2007, J Bio Chem., 2009).
Novel Therapeutic Approaches Targeting Cancer Epigenetic Processes:My laboratory is also interested in pharmacologic modulation of epigenetic processes in cancer. In particular, we are studying the oncogenic Polycomb-mediated gene silencing activity in cancer and its interplay with histone deacetylation and DNA methylation. We are also developing novel chemical approaches that target histone modifications such as histone methylation and deacetylation, leading to interventions of key cancer pathways and efficient apoptosis induction. We have discovered DZNep and its anlogous as a new class of chromatin modifiing compound that have therapeutic potential (PNAS, 2005; J Bio Chem., 2006, Genes & Devel., 2007, Cancer Cell, 2008, Genes & Devel., 2009, Cell Death and Differentiation, 2009)
Selected Publications
- 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.
- Wenyu Wang , Yen-An Tang , Qian Xiao , Wee Chyan Lee , Bing Cheng , Zhitong Niu, Gokce Oguz, Min Feng , Puay Leng Lee , Baojie Li , Zi-Huan Yang , Yu-Feng Chen , Ping Lan , Xiao-Jian Wu , Qiang Yu. Stromal induction of BRD4 phosphorylation Results in Chromatin Remodeling and BET inhibitor Resistance in Colorectal Cancer. Nat Comm. 2021. PMID: 34290255
- Tang YA, Chen YF, Bao Y, Mahara S, Yatim SMJM, Oguz G, Lee PL, Feng M, Cai Y, Tan EY, Fong SS, Yang ZH, Lan P, Wu XJ, Qiang Yu "Hypoxic tumor microenvironment activates GLI2 via HIF-1α and TGF-β2 to promote chemoresistance in colorectal cancer." Proc Natl Acad Sci U S A 2018 06 26 ; 115(26) : E5990-E5999
- Jian Yuan Goh, Min Feng, Wenyu Wang, Gokce Oguz1,2, 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 Sarma1, 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
- 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
- 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 Yang1 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
- 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