CHEN Leilei Polly

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

csicl[at]nus.edu.sg

The human genome encodes RNA molecules that instruct the behaviour of cancer cells. Leveraging on the next-generation sequencing technologies, well-established cancer cell lines and animal models, Dr Polly Leilei Chen’s group aims to identify the harmful changes that will occur in RNA molecules after it is made from DNA. It is critical to uncover how these changes trigger a cell to develop into cancer which can eventually lead to the unsatisfactory treatment outcomes for patients with cancers (particularly esophageal, stomach, colon and liver cancer). The long-term goal of Dr Chen’s team is to develop novel cancer therapies targeting these cancer-associated RNA changes.

Research

My research interest has been centered on understanding the changes in RNA (particularly adenosine-to-inosine RNA editing and splicing) in human cancers and translating this new knowledge to aid early detection and intervention as well as treatment.

RNA editing, which cannot be detected by either whole-genome sequencing (WGS) or exome sequencing, introduces changes in RNA sequences. In humans, the most common type of editing is the conversion of adenosine to inosine (A-to-I), which is catalysed by the double-stranded RNA-specific adenosine deaminase that acts on RNA (ADAR) family of proteins. 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. Our current research focuses have been placed on understanding the causes of RNA editing dysregulation in cancer, the functional impacts of RNA editing changes on cancer initiation and progression, and the therapeutic potential of modulating RNA editing activity in cancer cells.

ADAR1 and/or ADAR2 proteins bind to double-stranded RNAs in the nucleus and convert adenosine (A) to inosine (I). Inosine is recognized as guanosine (G) by most cellular machineries, such as splicing and translation machineries.

Lab Members

Selected Publications

1. Song Y, An O, Ren X, Chan TH, Tay DJ, Tang SJ, Han J, Hong HQ, Ng VHE, Ke X, Shen H, Pitcheshwar P, Lin SJ, Leong KW, Molias FB, Yang H, Kappei D, Chen L. RNA editing mediates the functional switch of COPA in a novel mechanism of hepatocarcinogenesis. Journal of Hepatology. Published: July 18, 2020. DOI:https://doi.org/10.1016/j.jhep.2020.07.021

2. Han J, An O, Hong H, Chan TH, Song Y, Shen H, Tang SJ, Lin JS, Ng VHE, Tay DJ, Molias FB, Pitcheshwar P, Yang H, Chen L. Suppression of Adenosine-to-Inosine (A-to-I) RNA Editome by Death Associated Protein 3 (DAP3) Promotes Cancer Progression. Science Advances,2020; 6, eaba5136.

3. 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. 2020;11(1):799.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

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

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.

Honors & Awards

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