Leong Yeh Chwan
I graduated with a BSc (hons) in Biotechnology in 2013. I worked as research assistant at the University of Malaya for 9 months and became interested in stem cell and epigenetic research. I am currently pursuing a PhD in stem cell and cancer biology at the University of Nottingham.
Full-time PhD. Expected completion in 2018
School Research Theme:
Reproductive Biology and Comparative Medicine
Cancer cell reprogramming: elucidating the molecular events during tumorigenesis.
Summary of Research:
Increasing evidence shows that accumulation of genetic and epigenetics abnormalities contribute to cancer development. Genetic mutations in oncogenes, tumour suppressor genes and genes related to genome stability have been extensively studied and implicated in tumorigenesis. In recent years, epigenetic dysregulation has been shown to promote tumorigenesis and play a vital role in cancer cells maintenance.
Acquisition of specific cell identity has been widely considered as an epigenetic process. Cells of different lineages acquired specific global epigenetic configurations during the developmental process enabling the expression of cell-specific genes. The epigenetic marks acquired during the differentiation process were previously regarded as irreversible. However, the recent breakthrough in reprogramming of differentiated cells into pluripotent stem cells (termed induced pluripotent stem cells, iPSCs) via ectopic expression of four transcription factors (Oct4, Sox2, Klf4 and Myc, termed OSKM) has demonstrated that cell identity can in fact be reverted into a more primitive state. Generation of iPSCs is regarded as a process involving a series of epigenetic events, which lead to the abolishment of somatic cell’s epigenetic marks and formation of new epigenetic configurations characteristic of pluripotency without altering the cell DNA sequence.
Recent studies demonstrated that cancer development and iPSC generation share numerous similarities. It have been frequently reported that the iPSC generation can potentially induce genomic and epigenetic aberrations and result in oncogenic transformation. Besides, the four factors used in somatic cell reprogramming have been directly or indirectly implicated in the development of various cancers. For instance, Myc is an oncogene, whose overexpression has been observed in various human cancers including lung carcinoma, breast carcinoma and rare cases of colon carcinoma. In addition, the inhibition of tumor-suppressor pathways, including p53 and Rb, has been shown to significantly enhance the reprogramming efficiency. Besides, numerous common pathways in both oncogenesis and somatic cell reprogramming have been shown to be overlapping. Therefore, the iPSC technology serves as a promising tool to elucidate the molecular mechanisms underlying oncogenesis transformation. By reprogramming cancer cells using the iPSC technology we can investigate the impacts of epigenetic regulations on cancer cells.
Dr Cinzia Allegrucci (School of Veterinary Medicine & Science)
Dr Anna Grabowska (School of Medicine)
Dr Ramiro Alberio (School of Bioscience)
Primary Funding Source:
Vice-Chancellor’s Scholarship for Research Excellence (International)
None to Date