Despite remarkable progress towards personalized human genome sequencing, much about the human genome remains unknown. Only 2% of the human genome codes for protein, yet many studies suggest that the remaining 98% may have non-coding functions and may be related to disease. Recently, tremendous advances in DNA sequencing throughput, speed, and cost have been made by next-generation sequencing, allowing the development of new genomic technologies for powerful ultra-high-throughput, genome-wide annotation of genomic elements. Towards this aim, the Fullwood lab focuses on human genome annotation, transcriptome characterization, and understanding transcription regulation, to promote human personal genomics. One of the uses of personal genomics is in better understanding cancer, which may lead to the development of better therapies with reduced side effects and novel biomarkers. Towards this end, we are focusing on genomic annotation of gastric and other cancer cell lines.
The Fullwood lab focuses on human genome annotation, transcriptome characterization, and understanding transcription regulation, to promote human personal genomics, particularly in cancer. In vivo, DNA is compacted into chromatin. The processes surrounding DNA are complex, and these “epigenetic” processes can include histone modifications, transcription factors that regulate gene expression. Cancer genome sequencing has revealed that many factors associated with epigenetic processes are mutated in cancers, and epigenetic processes have been targeted by specific drugs. In addition, RNA has been found to be more complex than previously thought, and long non-coding RNAs, previously thought of as “transcriptional noise”, have been found to play roles in cancer.
Chromatin immunoprecipitation (ChIP) with sequencing and RNA sequencing are powerful tools that rely on new next-generation sequencing approaches to provide deep insights into epigenetic processes. Moreover, Dr Fullwood’s research on developing Chromatin Interaction Analysis with Paired-End Tag sequencing (ChIA-PET) has suggested that chromatin interactions, which are regions of the genome that are far apart in the linear genome sequence but come together in close 3-dimensional spatial proximity, may constitute common mechanisms for gene regulation.
Dr Fullwood’s current work focuses on using ChIP sequencing, RNA sequencing, and ChIA-PET on a gastric cancer cell model, as well as other cancer cell models, to elucidate the detailed epigenomic profiles, allowing for new insights into possible cancer-associated biomarkers and cancer therapies. In addition, Dr Fullwood is interested in continuing to develop and refine new genomic technologies to understand chromatin and transcription.
- The ENCODE Project Consortium. An Integrated Encyclopedia of DNA Elements in the Human Genome, Nature. 2012
- Djebali et al. Landscape of Transcription in Human Cells, Nature. 2012
- Li et al. Extensive promoter-centered interactions provide higher-order framework for transcription regulation in human cells, Cell. 2012
- Goh, Y.*, Fullwood, M.J*†. Poh, H.M., Peh, S.Q., Ong, C.T., Zhang, J.Y., , Ruan, X., Ruan, Y.†. Chromatin Interaction Analysis with Paired-End Tag Sequencing (ChIA-PET) for mapping chromatin interactions and understanding transcription regulation, J. Vis. Exp. 2012 *Co-first authors and †co-corresponding authors.
- Fullwood, M.J., Lee, J., Lin, L., Li, G., Huss, M., Ng, P., Sung, W-K., Shenolikar, S. Next-generation Sequencing of Apoptotic DNA Breakpoints Reveals Association with Actively Transcribed Genes and Gene Translocations, PLoS ONE. 2011
- Fullwood, M.J.*, Han, Y.Y.*, Wei, C.L., Ruan, X., Ruan, Y. Chromatin Interaction Analysis using Paired-End Tag Sequencing, Current Protocols in Molecular Biology. 2010 *Co-first authors
- Li, G.*, Fullwood, M.J.*, Han X.*, et al. ChIA-PET Tool for Comprehensive Chromatin Interaction Analysis with Paired-End Tag Sequencing, Genome Biology. 2010 *Co-first authors.
- Fullwood, M.J., et al. The Oestrogen Receptor a-mediated Human Chromatin Interactome, Nature. 2009
- Fullwood, M.J., Wei, C.L., Liu, E. T., Ruan, Y. Ultra-High-Throughtput Sequencing of Paired-End Tags (PET) for Transcriptome and Genome Analyses, Genome Res. 2009
- Fullwood, M.J., Ruan, Y. ChIP-based Methods for the Identification of Long-Range Chromatin Interactions, Journal of Cellular Biochemistry. 2009
|Name||Melissa Jane FULLWOOD|
|Affiliations||Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore
Nanyang Assistant Professor, School of Biological Sciences, Nanyang Technological University
Joint Principal Investigator, Institute of Molecular and Cell Biology, A*STAR Singapore
|Institute||Degree (if applicable)||Year(s)|
|National University of Singapore, Singapore||Ph.D.||2009|
|Stanford University, USA||B.Sc.(Hons)||2005|
|•||Lee Kuan Yew Post-Doctoral Fellow, A*STAR-Duke-NUS NRP||2010 – 2012|
|•||Adjunct Research Fellow, Department of Biochemistry, National University of Singapore||2011 – 2012|
|•||Adjunct Post-Doctoral Fellow, Genome Institute of Singapore||2011 – 2012|
|•||Post-Doctoral Fellow, Duke-NUS||2009 – 2010|
|•||Research Fellow, Genome Institute of Singapore||2009|
|•||Research Officer, Genome Institute of Singapore||2005 – 2006|
Computational analysis of chromatin topology and transcriptomic variation in leukemia and breast cancer.
Investigation of chromatin interactions in the pathogenesis of leukaemia.
The effects of the relationship between non-coding RNAs and chromatin interactions on cancer progression.
Using high throughput sequencing data to study transcription factors in gastric cancer.
Senior Laboratory Executive
To process clinical samples and create transcriptome libraries for studies in haematopoiesis and leukemia, Member of the RNA Biology Centre.
FAM Wee Nih @ Winnie Fam
To understand RNA biology and therapeutics in haematopoiesis and leukemia under the RNA Epigenomic Core Project.
1) Disruption of TAD boundaries in cancer.
2) Bivalent chromatin interactions.
LOH Yan Ping
Carrying out 4C experiments to study chromatin interactions in cancer.
TNG Jia Qi
Carrying out CRISPR experiments to study chromatin interactions in human cancer cell lines.
|•||A*STAR/SNAS Young Scientist Award||2014|
|•||National Research Foundation (NRF) Fellowship||2013|
|•||A*STAR Phillip Yeo Prize for Outstanding Achievement in
|•||Regional Winner (International), GE & Science Prize
for Young Life Scientists
|•||Lee Kuan Yew Post-Doctoral Fellowship||2010|
|•||L’Oreal-UNESCO for Women in Science Singapore National
|•||A*STAR National Science Scholarship (A*STAR NSS PhD)||2006|
|•||Phi Beta Kappa||2005|
|•||A*STAR National Science Scholarship (A*STAR NSS BS)||2002|