CHEN Leilei Polly

The main focus of Dr Chen Leilei’s group is to study the transcriptome instability of human cancers, particularly hepatocellular carcinoma (HCC), the major malignancy of the liver and the third leading cause of cancer-related deaths globally. While the epidemiological risk factors for HCC are well known, the molecular mechanisms underlying development of liver cancer are not well characterized. It is especially important to understand the potentially reversible epigenetic mechanisms, since these changes are novel candidates for therapeutic targeting. One type of epigenetic change is RNA editing, defined as an alteration of RNA sequences.

csicl@nus.edu.sg

Biosketch

Principal Investigator, Cancer Science Institute of Singapore
NUS President Assistant Professor, Department of Anatomy, NUS

Year(s) Degree (if applicable) Institute
2002 M.D. (First-Class Honor) Medical College of Jiangsu University, China
2010 Ph.D. The University of Hong Kong
2018 – Present EMBO Young Investigator
2017 – Present Editorial Board Member, Oncology Reports and Reviews
2016 – Present Member, The RNA Society
2015 – Present Affiliate Member, National University Cancer Institute, Singapore (NCIS)
2009 – Present Associate Member, American Association for Cancer Research (AACR)
2019 EMBO Young Investigator Program (YIP)
2018 NUHS-Mochtar Riady Pinnacle Awards-High Achiever Award 2018
2017 Yong Loo Lin School of Medicine Young Research Of the Year Award
2015 President Assistant Professorship, National University of Singapore
2014 Science and Technology Award of Higher Education of China (Second Class), Ministry of Education, China
2014 NUS Young Scientist Award, National University of Singapore

Research

RNA editing is an integral step in generating the diversity and plasticity of cellular RNA signatures. In humans, the most frequent type of editing is the conversion of adenosine (A) to inosine (I), which is catalyzed by the double-stranded RNA (dsRNA)-specific ADAR (Adenosine DeAminase that act on RNA) family of protein. This process of recoding of translated exons, widespread editing of repetitive sequence elements and sequence modification of microRNA (miRNA) can lead to specific amino acid substitutions, alternative splicing and changes in gene expression levels. With the advent of high-throughput transcriptome sequencing, many editing sites potentially associated with cancer development have been identified. We previously highlighted a tight link between transcriptome instabilities in the form of excessive or defective RNA editing activity and cancer development. Our current research interests have been centred on understanding the causes of RNA editing dysregulation in cancer, the functional impact of RNA editing events on cancer initiation and progression, and the therapeutic potential of modulating RNA editing activity.

Lab Members

Selected Publications

1. Tang SJ, Shen H, An O, Hong HQ, Li J, Song Y, Han J, Tay DJ, Ng VHE, Molias FB, Leong KW, Pitcheshwar P, Yang H, Chen L. Cis- and trans-regulation of pre-mRNA splicing by RNA editing enzymes: influencing cancer development. Nature Communications, In Press.

2. Hong H, An O, Chan TH, Ng VHE, Kwok HS, Lin JS, Qi L, Han J, Tay DJ, Tang SJ, Yang H, Song YY, Molias FB, Tenen DG, Chen L. Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer. Nucleic Acids Res, 2018 Sep 6;46(15):7953-7969.

3. Qi L, Song Y, Chan TH, Yang H, Lin CH, Tay ST, Hong H, Tang SJ, Tan KT, Huang XX, Lin JS, Ng VHE, Maury JJP, Tenen DG, Chen L. An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer. Nucleic Acids Res. 2017 Oct 13;45 (18):10436-10451.

4. Chan TH, Qamra A, Tan KT, Guo J, Yang H, Qi L, Lin JS, Ng VH, Song Y, Hong HQ, Tay ST, Liu Y, Lee J, Rha SY, Feng Z, So JB, Tean TB, Guan YK, Rozen S, Tenen DG, Tan P, Chen L. ADAR-mediated RNA editing predicts progression and prognosis of Gastric Cancer. Gastroenterology. 2016, 151(4):637-650.

5. Hong HQ, Lin JS, Chen L. Regulatory factors governing Adenosine-to-Inosine (A-to-I) RNA editing. Biosci Rep. 2015, 35(2).

6. Qin YR, Qiao JJ, Chan TH, Zhu YH, Li FF, Liu HB, Fei J, Li Y, Guan XY, Chen L. Adenosine-to-inosine RNA editing mediated by ADARs in Esophageal squamous cell carcinoma (ESCC). Cancer Res. 2014 74(3):840-851.

7. Chan TH, Lin CH, Qi L, Fei J, Li Y, Yong KJ, Liu M, Song Y, Chow RK, Ng VH, Yuan YF, Tenen DG, Guan XY, Chen L. A disrupted RNA editing balance mediated by ADARs (Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma. Gut. 2014, 63(5):832-43.

8. Qi LH, Chan HM, Tenen DG, Chen L. RNA editome imbalance in hepatocellular carcinoma. Cancer Res, 2014,74(5):1301-1306.

9. Qiao JJ, Chan TH, Qin YR, Chen L. ADAR1: a promising new biomarker for Esophageal Squamous Cell Carcinoma. Expert Rev Anticancer Ther, 2014, 14(8):865-868.

10. Chen L, Li Y, Lin C, Chan TH, Chow RK, Song Y, Liu M, Yuan YF, Fu L, Kong KL, Qi L, Li Y, Zhang N, Tong AH, Kwong DL, Man K, Lo CM, Lok S, Tenen DG, Guan XY. Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. Nature Med, 2013, 19(2):209-16.