Yvonne TAY

In addition to genomic alterations, aberrant changes in RNA regulation represent another mechanism to disrupt the function of critical oncogenes or tumor suppressors and thus contribute to tumorigenesis. MicroRNAs are short non-coding RNAs which regulate gene expression and have been functionally linked to multiple human cancers. Work by our group and others has demonstrated that RNA transcripts co-regulate each other by competing for shared microRNAs, thus acting as competing endogenous RNAs (ceRNAs). My lab will focus on investigating the role that these RNA:RNA regulatory interactions play in tumorigenesis. Moreover, as several non-coding RNA species have been shown to possess ceRNA activity, we expect that the study of regulatory ceRNA interactions will facilitate the annotation of the non-coding transcriptome. This work will lead to important insights into this previously uncharacterized dimension of RNA:RNA interactions and the discovery of novel oncogenes and/or tumor suppressors, in turn providing potential diagnostic or therapeutic targets.

The importance of the non-coding transcriptome has become increasingly clear in recent years – comparative genomic analysis has demonstrated a significant difference in genome utilization among species (for example, the protein-coding genome constitutes almost the entire genome of the unicellular yeast, but only 2% of mammalian genomes), and the non-coding transcriptome is frequently dysregulated in cancer and is often the target of recurrent genetic alterations. These observations suggest that the non-coding transcriptome is of critical importance in determining the greater complexity of higher eukaryotes and in disease pathogenesis.

The dysregulated expression of critical genes is one of the driving forces that transforms a normal cell into a cancer cell. In addition to genomic alterations, aberrant changes in post-transcriptional regulation represent another mechanism to modify gene function and thus contribute to tumorigenesis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to recognition sites on target transcripts. MiRNAs play important roles in a plethora of biological processes and have been functionally linked to multiple human cancers.

Recently, work by our group and others has demonstrated the existence of a previously uncharacterized dimension to miRNA:target interactions. While miRNA studies have largely examined the effect of individual miRNAs on target transcripts, we have shown that RNA transcripts can co-regulate each other by competing for shared miRNAs, acting as competing endogenous RNAs (ceRNAs) and forming a novel post-transcriptional regulatory layer.

Although remarkable advances have been made in the past few years toward our understanding of miRNA and ceRNA-dependent gene regulation, it is increasingly clear that we have barely begun to understand the complexities and dynamics of these interactions. My lab will focus on investigating the role that these RNA:RNA regulatory interactions play in altering the levels of critical oncogenes or tumor suppressor genes. Moreover, as increasing experimental evidence suggests that several non-coding RNA species possess ceRNA activity, we expect that the study of regulatory ceRNA interactions will facilitate the annotation of the non-coding transcriptome. This work will lead to important insights into the regulation of tumorigenesis and the discovery of novel oncogenes and/or tumor suppressors, in turn providing potential diagnostic or therapeutic targets.

Selected Publications:

  1. Tay Y, Tan SM, Karreth FA, Lieberman J, Pandolfi PP. (2014) Characterization of dual PTEN and p53-targeting microRNAs identifies miR-638/Dnm2 as a two-hit oncogenic locus. Cell Rep. Epub Jul 31.
  2. Tay Y, Rinn J, Pandolfi PP. (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature. 505, 344-352.
  3. Tay Y*, Song SJ*, Pandolfi PP. (2013) The Lilliputians and the Giant: An emerging oncogenic microRNA network that suppresses the PTEN tumor suppressor in vivo. MicroRNA 2(2), 127-136.
  4. Ala U, Karreth FA, Bosia C, Pagnani A, Taulli R, Leopold V, Tay Y, Provero P, Zecchina R, Pandolfi PP. (2013) Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments. Proc Natl Acad Sci U S A 110(18), 7154-7159.
  5. Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, Di Cunto F, Lieberman J, Rigoutsos I, Pandolfi PP. (2011) Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147, 344–357. o Selected by Faculty of 1000
  6. Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, DeNicola G, Webster KA, Weiss D, Perez-Mancera PA, Krauthammer M, Halaban R, Provero P, Adams DJ, Tuveson DA, Pandolfi PP. (2011) In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147, 382–395.
  7. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. (2011) A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146(3), 353-358. o Selected by Faculty of 1000
  8. Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I. (2008) MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455(7216),1124-1128. o Selected by Faculty of 1000
  9. Tay Y*, Tam WL*, Ang YS*, Gaughwin PM, Yang HH, Wang W, Liu R, George J, Ng HH, Perera RJ, Lufkin T, Rigoutsos I, Thomson AM, Lim B. (2008) MicroRNA-134 modulates the differentiation of mouse embryonic stem cells, where it causes post-transcriptional attenuation of Nanog and LRH1. Stem Cells 26(1), 17-29.
  10. Miranda KC*, Huynh T*, Tay Y*, Ang YS*, Tam WL, Thomson AM, Lim B, Rigoutsos I. (2006) A pattern-based method for the identification of microRNA binding sites and their corresponding heteroduplexes. Cell 126(6), 1203-1217.* Co-first authors
Name Yvonne TAY
Affiliations Principal Investigator, Cancer Science Institute of Singapore, NUS
President Assistant Professor, Department of Biochemistry, NUS
Email csitmsy[at]nus.edu.sg

Education

Institute Degree (if applicable) Year(s)
National University of Singapore (NUS) B.Sc 2003
Genome Institute of Singapore and NUS Ph.D. 2008

Professional Experience

Postdoctoral fellow, Experimental Therapeutics Centre, A*STAR 2008
Postdoctoral fellow, Institute of Medical Biology, A*STAR 2009
Postdoctoral fellow, Harvard Medical School 2010 – 2014

Anastasiia FADIEIEVA

PhD
Research Fellow

Role of non-coding RNAs and chromatin modifications in mediating oncogenic processes in cancer development and progression

CHAN Jia Jia

PhD
Research Fellow

Role of RNA:RNA and RNA:protein interactions in the post-transcriptional regulation of key proto-oncogenes and tumor suppressor genes in cancer

Rajendra Babu KAMESH

PhD
Research Fellow

Post-transcriptional modifications of RNA in cancer development and progression

ZHANG Bin

PhD
Research Fellow

Role of post-transcriptional regulations in the tumorigenesis

LIM Chun You

PhD
Research Assistant

Role of coding and non-coding competing endogenous RNAs in the post-transcriptional regulation of key proto-oncogenes and tumor suppressor genes in cancer

Cassandra CHEW

Senior Laboratory Executive

Role of coding and non-coding competing endogenous RNAs in the post-transcriptional regulation of key proto-oncogenes and tumor suppressor genes in cancer

Yvonne - Desi_CSI pic

Desi

PhD Student

Role of RNA:RNA and RNA:protein interactions in the post-transcriptional regulation of key proto-oncogenes in cancer

KWOK Zhi Hao

PhD Student

Role of RNA:RNA and RNA:protein interactions in the post-transcriptional regulation of key tumor suppressor genes in cancer

Young Scientist Award 2015
Singapore National Research Foundation Fellowship 2015
NUS President’s Assistant Professorship 2014
Special Fellowship, Leukemia & Lymphoma
Society
2011-2014
Philip Yeo Prize for Outstanding Achievement in Research,
A*STAR Biomedical Research Council, Singapore
2009
A*STAR Graduate Scholarship, Agency for Science,
Technology and Research, Singapore
2004-2008