Chromatin Interactions in Cancer

DESCRIPTION OF LAB RESEARCH WORK
Precision cancer medicine relies on understanding the individual workings of each cancer and person in order to develop tailored therapies. Chromatin interactions are regions of the genome that are far apart in the linear genome sequence but come together in close 3-dimensional spatial proximity, and may constitute common mechanisms for gene regulation. Our lab’s main hypothesis is that epigenetic factors, transcription factors, and non-coding RNA are mutated in cancer, leading to dysregulation of chromatin interactions and consequent dysregulated transcription and cancer progression. Artificial intelligence on patient epigenomics datasets in order to predict epigenomic events including chromatin interactions may be able to eventually provide prognostic information as well as aid in the selection of epigenetic therapies for patients. We study this hypothesis within the system of all cancers, but with a focus on blood cancers as compared with normal blood formation.

LAB MEMBERS

	LEAD PI Melissa Jane Fullwood ​Nanyang Assistant Professor Email: mfullwood@ntu.edu.sg Phone: (65) 6516 5381
	Cao Fan Research Fellow Email: caofan@nus.edu.sg
	Deepak Babu Research Fellow Email: csideb@nus.edu.sg
​	Sukru Gulluoglu Research Fellow Email: sgulluoglu@gmail.com
	​​Benny Wang PhD Student Email: S150064@e.ntu.edu.sg​
	Lingshi Kong PhD Student Email: lingshi001@e.ntu.edu.sg
	See Yi Xiang PhD Student Email: seey0018@ntu.edu.sg
	Zhang Ying PhD Student Email: zhangy@u.nus.edu
	Tng Jia Qi Laboratory Executive Email: csitjq@nus.edu.sg​
	Winnie Fam Laboratory Executive Email: csifwnw@nus.edu.sg

CURRENT PROJECTS

• Artificial intelligence for predicting chromatin interactions and epigenomi​c phenomena
• Understanding the roles of genomic silencers and chromatin interactions​
• Characterization of chromatin interactions in Acute Myeloid Leukemia
• Investigating the roles of oncogenic transcription factor c-MYC in chromatin interactions
• Uncovering the relationships between chromatin interactions and RNA

PUBLICATIONS
Full list of publications can be found here​

• Lee, D.P. et al., A Robust CTCF-Based Chromatin Architecture Underpins Epigenetic Changes in the Heart Failure Stress-Gene Response., Circulation., 2019.
• See, Y., Wang, B., and Fullwood, M.J., “Chromatin Interactions and Regulatory Elements in Cancer: From Bench to Bedside,” Trends in Genetics, 2019.
• Teoh, P.J. et al., “Aberrant hyperediting of myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis”, Blood, 2018.
• Xie, J.J. et al., “Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over-Expressed and Oncogenic in Squamous Cell Carcinoma”, Gastroenterology., 2018.
• Yan, T. et al., “HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis”, Nat Commun., 2018.
• Cao, F. et al., “Super-Enhancers and Broad H3K4me3 Domains Form Complex Gene Regulatory Circuits Involving Chromatin Interactions”, Sci. Rep., 2017.
• Ooi, W.F. et al., “Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity”, Nat. Commun., 2016.
• ​Akincilar, S. et al., “Long-range chromatin interactions drive mutant Tert promoter activation”, Cancer Discovery, 2016.
• Choy, J.Y., Boon, P.L., Bertin, N., and Fullwood, M.J., “A Resource of Ribosomal RNA-depleted RNA-Seq data from Different Normal Adult and Fetal Human Tissues”, Sci. Data, 2015.
• Babu, D. and Fullwood, M.J., “3D Genome Organization in Health and Disease: Emerging Opportunities in Cancer Translational Medicine”, Nucleus. 2015.​