PROJECT SUMMARY

The human genome is built with strings of DNA spanning 2 meters. However, a single nucleus of a mammalian cell is only on the scale of 10μm. How the human genome is folded and packaged into the nucleus is still a mystery. We are studying  how the human genome forms 3D structures in the nucleus and how these human genome 3D structures instruct transcription (the process of transcribing DNA code into message RNA). Especially, we focus on Myeloid Dysplastic Syndromes (MDS) as our study subject. We are studying if there is any change in the folding and packaging of genome in MDS. We especially want to explore if the disordered folding in the genome of MDS can contribute to the development of MDS. It is also proposed that DNA methylation – a chemical modification occurs on CG sequence – may play a role in shaping and guiding genome structure. Decitabine – a drug that erases all DNA methylation marks in the genome – is widely used as the first line therapy for MDS. We thus will also explore how Decitabine alters the genome folding in MDS and contributes to the therapy response in MDS patients.