Caroline Guat Lay LEE

Associate Professor

Affiliations

Associate Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS.
Principal Investigator, National Cancer Centre.
Associate Professor, Duke-NUS Graduate Medical School.
Supervisor, NUS Graduate School for Integrative Sciences and Engineering (NGS).

Biodata

Caroline Lee graduated with PhD from Baylor College of Medicine and did her post-doctoral training with Dr. Michael Gottesman at the National Cancer Institute, National Institutes of Health. She currently also holds joint appointment as Principal Investigator at the National Cancer Centre as well as an Associate Professor at the Cancer and Stem Cell Biology Program at Duke-NUS Graduate Medical School. She has ~100 peer reviewed publications and research focuses on the functional genomics of hepatocellular carcinoma (HCC) and pharmacogenetics. Her laboratory identified FAT10 as a molecule that is over-expressed in HCC and other inflammation associated cancers and demonstrated it plays a role in TNF-α induced chromosome instability. Employing next-generation sequencing (NGS), the laboratory has also characterized HBV in 48 HCC patients and found that integration of HBV into chromosome 10 is associated with poor prognosis. Using, chromatin immunoprecipitation coupled with microarray/NGS, the laboratory has demonstrated that HBX, a protein of HBV can modulate the binding of p53, an important ‘guardian-of-the-genome’ to the regulatory region of genes. Another strong research program in her laboratory is mining the human genome databases to identify polymorphisms that have potential to be functionally important to facilitate the association with diseases and drug response. Her laboratory identified signatures of recent positive selection in the drug transporter gene(s) and demonstrated that these polymorphisms may represent important polymorphisms that may change the function of the gene. The laboratory has developed a comprehensive, well-annotated, integrated potentially functional SNP (pfSNP) web-resource that facilitates better hypothesis generation through knowledge synthesis mediated by better data integration and a user-friendly web interface. Since its publication in Oct 2010, this web-resources has garnered >8,500 visits from researchers from more than 90 countries.

Research Interest

* Characterization of FAT10 in tumorigenesis and developing FAT10 as a target for inflammation-associated cancer.
* Haracterization of HBV in HCC.
* Elucidate the role of HBX in deregulating miRNA and gene expression.
* Identify Biomarkers for HCC.
* Continual update of the pfSNP web-resource including the inclusion of new algorithm and resources.
* Identify SNP biomarkers for predicting population differential response to drugs.

Selected Publications

  1. Zihua Wang, Baoshuang Wang, Kun Tang, Edmund JD Lee, Samuel S Chong, and Caroline GL Lee*. A functional polymorphism within the MRP1 gene locus identified through its genomic signature of positive selection. Human Molecular Genetics 14(14): 2075-2087 (2005).

  2. Yu WANG, Yiwei LU, Soo Ting TOH, Wing-Kin SUNG, Patrick TAN, Pierce CHOW, Alexander YF CHUNG, London L. P. J OOI and Caroline G.L. LEE*. Lethal-7 is down-regulated by the Hepatitis B virus x protein and targets Signal Transducer and Activator of Transcription 3. Journal of Hepatology 53: 57–66 (2010).

  3. Jingbo Wang, Mostafa Ronaghi, Samuel S Chong, Caroline GL Lee*. pfSNP: An Integrated Potentially Functional SNP Resource that facilitates Hypotheses Generation through Knowledge Syntheses. Human Mutation 32(1):19-24 (2011).

  4. Jianwei Ren, Yu Wang, Yun Gao, Shalin BK Mehta and Caroline GL Lee*. FAT10 mediates the effect of TNF-α in inducing chromosomal instability. Journal of Cell Science 124, 3665–3675 (2011).

  5. Cheryl CHAN, Yu WANG, Pierce K.H. CHOW, Alexander Y.F. CHUNG, London L.P.J. OOI, and Caroline G. LEE*. Altered Binding Site Selection of P53 Transcription Cassettes by Hepatitis B Virus X Protein. Molecular and Cellular Biology 33(3):485-497 (2013).

  6. Soo Ting Toh, Yu Jin, Lizhen Liu, Jingbo Wang, Farbod Babrzadeh , Baback Gharizadeh, Mostafa Ronaghi, Han Chong Toh, Pierce Kah-Hoe Chow, Alexander Y-F Chung, London L.-P- J Ooi, Caroline G-L Lee*. Deep sequencing of the Hepatitis B Virus in Hepatocellular Carcinoma patients reveals enriched integration events, structural alterations and sequence variations. Carcinogenesis 34(4): 787–798 (2013)
* = Senior Corresponding Author