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Our current research interests focus on 2 major fields of Functional Genomics of Hepatocellular Carcinoma (HCC) and Population/Pharmaco-genetics.  In the field of HCC, our laboratory is interested in employing next-generation genetic, molecular, cellular and computational approaches to elucidate clinically important genes, lncRNAs, miRNAs, circRNAs that are dysregulated in HCC and associated with poorer prognosis.  One of the genes that our laboratory identified to be highly over-expressed in HCC is FAT10, the gene in this proposal.  Our laboratory is the first to show that FAT10 is over-expressed in HCC and other inflammation-associated cancers and we also identified that it plays a role in tumorigenesis through interacting non-covalently with MAD2 to delocalize MAD2 from the kinetochore causing aneuploidy and ultimately tumorigenesis.  We are in the process of investigating the role of FAT10 in linking inflammation and metabolism in cancer.

In the field of Population/Pharmaco-genetics, our laboratory is interested in identifying functionally important polymorphisms that are associated with drug response.  Integrating potentially functional SNP resource developed in our laboratory with gene-pathway information and analyzing population differences of SNPs, we develop an algorithm to identify drug/drug groups that potentially exhibit population differences in response using SNP data mining and analytics.  We are in the process of validating the algorithm with real-world clinical data and incorporating deep learning/AI to improve the algorithm of predicting drug response.

Publications (out of >100):

Huang Weitai, SKANDERUP and Caroline G. Lee*.  Advances in Genomic Hepatocellular Carcinoma Research.  GigaScience 7:1-22 (2018) 

Yu Jin; Jingbo Wang; Maulana Bachtiar; Samuel S. Chong; Caroline G. L. Lee*. Architecture of Polymorphisms in the Human Genome Reveals Functionally Important and Positively Selected Variants in Immune-Response and Drug Transporter Genes.  Human Genomics 2018 Sep 15;12(1):43.

Lee Wai Yeow, Maulana Bachtiar, Chan Siew Choo, Cheryl and Caroline G Lee*. Comprehensive Review of Hepatitis B Virus-associated Hepatocellular Carcinoma Research through Text Mining and Big Data Analytics.  Biological Reviews 2018 Aug 13. doi: 10.1111/brv.12457

Cheryl CHAN, Thomas THURNHERR, Jingbo WANG,  Xavier GALLART-PALAU, Siu Kwan SZE, Steve ROZEN and Caroline G. LEE.  Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein.  Molecular Oncology 2016 10(8):1183-1195 (2016)

Thomas Thurnherr, Way-Champ Mah, Zhengdeng Lei, Yu Jin, Steven G. Rozen & Caroline G. Lee. Differentially Expressed miRNAs in Hepatocellular Carcinoma Target Genes in the Genetic Information Processing and Metabolism Pathways.  Scientific Reports 6: 20065 (2016).

Ling Li, David Ng, Way-Champ Mah, Francisca Almeida, Siti Aishah Rahmat, Vinay Kumar Rao, Shi Chi Leow, Federica Laudisi, Meng Teng Peh, Amanda Goh, John Lim, Graham Wright, Alessandra Mortellaro, Reshma Taneja, Florent Ginhoux, Caroline Lee, Philip K Moore, and David Lane.  A unique role for p53 in the regulation of M2 macrophage polarization.  Cell Death and Differentiation 22(7):1081-1093 (2015)

Yan Xiang, Zachary E. Stine, Jinsong Xi, Yunqi Lu, Roddy S. O’Connor, Brian J. Altman, Annie L. Hsieh, Arvin M. Gouw, Ajit G. Thomas, Ping Gao, Linchong Sun, Libing Song, Benedict Yan, Barbara S. Slusher,  Jingli Zhuo, London L. Ooi, Caroline G.L. Lee, Anthony Mancuso, Andrew S. McCallion, Anne Le, Michael C. Milone, Stephen Rayport, Dean W. Felsher, Chi V. Dang.  On-target inhibition of glutaminase diminishes cell autonomous tumorigenesis.  J Clin Invest. 2015. 125(6): 2293-2306

Betty L. Slagle, Ourania M. Andrisani, Michael J. Bouchard, Caroline G. L. Lee, J.-H. James Ou, and Aleem Siddiqui. Technical Standards for Hepatitis B Virus X protein (HBx) Research.  Hepatology 61:1416-1424 (2015)

Steven Setiawan Theng, Wei Wang, Way Champ Mah, Cheryl Chan, Jingli Zhuo, Yun Gao, Haina Qin, Liangzhong Lim, Samuel S. Chong, Jianxing Song and Caroline G.L. Lee*. Disruption of FAT10-MAD2 binding inhibits Tumor Progression Proc. Natl. Acad. Sci. U.S.A. 111(49):E5282-5291 (2014).  Featured in ~10 News Reports.

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).

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).

Yu WANG, Han Chong TOH, Pierce Chow, Alexander YF Chung, David Meyers, Philip A. Cole,  London L. P. J Ooi, Caroline G.L. LEE*.  MicroRNA-224 is Up-regulated in Hepatocellular Carcinoma through Epigenetic Mechanisms.  FASEB J 26(7): 3032-3041 (2012)

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).  Featured in the ‘In this Issue’.

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). 

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)

Wing-Kin SUNG, Yiwei LU, Charlie WH LEE, Dongwei ZHANG, Mostafa RONAGHI, Caroline GL LEE*.  Deregulated Direct Targets of the Hepatitis B Viral (HBV) protein, HBx, identified through chromatin immunoprecipitation and expression microarray profiling. J. Biol. Chem  (2009); 284: 21941 – 21954.

Yu Wang, Alvin T. C. Lee, Joel Z. I. Ma, Jingbo Wang, Jianwei Ren, Yuchen Yang, Erwin Tantoso, Kuo-Bin Li, London L.P.J Ooi, Patrick Tan and Caroline G. L. Lee*.  Profiling microRNA Expression in Hepatocellular Carcinoma reveals microRNA-224 Upregulation and Apoptosis Inhibitor-5 as a microRNA-224-Specific Target.  J. Biol. Chem. 283:13205-13215 (2008)

Zihua Wang, Jingbo Wang, Erwin Tantoso, Baoshuang Wang, Amy YP Tai,  London L.P.J Ooi, Samuel S Chong, and Caroline GL Lee*.  Signatures of Recent Positive Selection at the ATP-Binding Cassette (ABC) Drug Transporter Superfamily Gene Loci.  Human Molecular Genetics 16(11):1367-1380 (2007)

Jianwei Ren, Alison Kan, Siew Hong Leong, London L.P.J Ooi, Kuan-Teh Jeang, Samuel S. Chong,  Oi Lian Kon and Caroline G.L. Lee*.  FAT10 plays a role in the regulation of chromosomal stability.  The Journal of Biological Chemistry 281: 11413 - 11421 (2006)

Dongwei Zhang, Kuan-Teh Jeang, Caroline G.L. Lee*.  P53 negatively regulates the expression of FAT10, a gene upregulated in various cancers.  Oncogene 25, 2318–2327 (2006)

Kun Tang, Li Peng Wong, Edmund JD Lee, Samuel S. Chong, Caroline G.L. Lee*.  Genomic Evidence for Positive Selection at the MDR1 Gene Locus. Human Molecular Genetics 13(8): 783-797 (2004)

Kun Tang, Soo-Mun Ngoi, Pai-Chung Gwee, John MZ Chua, Edmund JD Lee, Samuel S. Chong and Caroline G. Lee*.  “Distinct Haplotype Profiles and Strong Linkage Disequilibrium in the MDR1 multidrug transporter gene locus in three Asian populations. Pharmacogenetics 12(6):437-450 (2002)