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Transcription and Chromatin Regulation in Cancer



DESCRIPTION OF LAB RESEARCH WORK
Our research is focused on the molecular mechanisms underscoring the activation of cancer driver genes and the role of non-coding RNAs in the progression of human cancers. Recent advances in whole-genome sequencing have led to the identification of several somatic, non-coding mutations in a wide variety of human cancers, some of which regulate the transcription of cancerassociated genes. Besides cis-regulatory mutations, non-coding RNAs such as lncRNAs also exert significant gene regulatory roles in cancer. Our lab aims to understand the role of inflammatory mediators in activating transcriptional programs that are critical for the malignant transformation of cancer cells. We will use high-throughput methods such as ChIP-seq, RNA-seq and chromosome conformation capture assays that are complemented by genome-editing strategies a well as in vivo functional assays, to uncover the impact of these factors in chromatin regulation and the transcriptional control of cancer development.

LAB MEMBERS
LEAD PI
Li Yinghui
Assistant Professor

Email: liyh@ntu.edu.sg
Phone:(65) 6316 2947
Office: SBS-05N-23
Lim Shen Kiat
Senior Research Fellow

Email: shenkiat.lim@ntu.edu.sg
Ng Yee Ching
Research Fellow

Email: yeeching.ng@ntu.edu.sg
Daniel Aron Ang
Research Officer

Email: angda@imcb.a-star.edu.sg
Andrea Budiman
Project officer

Email: andrea.budiman@ntu.edu.sg
Nicholas Sim
PhD Student

Email: Yangunic001@e.ntu.edu.sg


CURRENT PROJECTS
  • Investigating the transcriptional and epigenetic reprogramming of driver mutations during cancer progression for the development of novel targeting strategies. This project aims to delineate the molecular events at cis-regulatory, driver mutations in cancer. We will address the role of cis-regulatory mutations as potential cancer biomarkers and identify key regulatory factors which can be putatively targeted for future cancer therapy.
  • Role of non-canonical NF-kB signaling in the transcriptional and epigenetic reprogramming of malignant cancers The nuclear factor κB (NF-κB) family of transcription factors regulates the expression of a broad range of inducible genes critical for various biological processes such as inflammation and immune responses. In particular, the aberrant activation of non-canonical NFκB signaling has been frequently observed in many human cancers. The primary goal of this research is to elucidate how deregulated non-canonical NF-B signaling regulates the gene expression programs of some of these cancers to promote their malignant development.


PUBLICATIONS
  • Xu XY*, Li Y*, Bharath SR, Ozturk MB, Loo BZL, Tergaonkar V and Song HW. (2018) Structural basis for reactivating the mutant TERT promoter by cooperative binding of p52 and ETS1. Nature Communications 9, 3183. (*Co-first author)
  • Li Y*, Cheng HS, Chng WJ and Tergaonkar V.* (2016) Activation of mutant TERT promoter by RAS-ERK signaling is a key step in malignant progression of BRAF-mutant human melanomas. Proc. Natl. Acad. Sci. USA 113(50), 14402-14407. (*Co-corresponding author)
  • Li Y* and Tergaonkar, V. (2016) Telomerase reactivation in cancers: Mechanisms that govern transcriptional activation of the wild-type vs. mutant TERT promoters. Transcription 7, 44-49. (*Corresponding author)
  • Li Y, Zhou Q-L, Sun W, Chandrasekharan P, Cheng HS, Ying Z, Lakshmanan M, Raju A, Tenen DG, Cheng SY, Chuang KH, Li J, Prabhakar S, Li M, and Tergaonkar V. (2015). Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation. Nature Cell Biology 17, 1327-38.
  • Highlighted in cover of October 2015 issue; featured in Cancer Discovery, Research Watch Nov 2015.
  • Yang BX, El Farran CA, Guo HC, Yu T, Fang HT, Wang HF, Schlesinger S, Seah YF, Goh GY, Neo SP, Li Y, Lorincz MC, Tergaonkar V, Lim TM, Chen L, Gunaratne J, Collins JJ, Goff SP, Daley GQ, Li H, Bard FA, and Loh YH. (2015). Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells. Cell 163, 230-45.
  • Koh CM, Khattar E, Leow SC, Liu CY, Muller J, Ang WX, Li Y, Franzoso G, Li S, Guccione E, and Tergaonkar V. (2015). Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity. Journal of Clinical Investigation 125, 2109-22.
  • Li, Y. and Tergaonkar, V. (2014). Noncanonical functions of telomerase: Implications in telomerase-targeted cancer therapies. Cancer Research 74, 1639-44.
  • Kundu, P., Teo, W. L., Korecka, A., Li, Y., D’Arienzo, R., Bunte, R.M., Berger, T., Arulampalam, V., Chambon, P., Mak, T.W., Wahli, W. and Pettersson, S. (2014). Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2-dependent Pathway. Plos Pathogens 10, e1003887.
  • Li, Y., Teo, W.L., Low, M.J., Meijer, L., Sanderson, I., Pettersson, S., and Greicius, G. (2014). Constitutive TLR4 signalling in intestinal epithelium reduces tumor load by increasing apoptosis in APCMin/+ mice. Oncogene 33, 369-77.
  • Li, Y., Kundu, P., Seow, S.W., de Matos, C.T., Aronsson, L., Chin, K.C., Kärre, K., Pettersson, S., and Greicius, G. (2012). Gut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in APCMin/+ mice. Carcinogenesis 33, 1231-1238.
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