The ability to convert any human cell to other specialised cell types of the body will allow the regeneration of tissues and organs as well as develop personalised therapies. It is now possible to reprogram biopsied human cells to become induced pluripotent stem (iPS) cells, which are very similar to embryonic stem (ES) cells. These cells are pluripotent and can potentially give rise to all cell types of the body. However, this cellular reprogramming method is highly inefficient and relies on the genetic manipulation of factors that have been associated with tumours. We aim to design reprogramming factors that are efficient and safe to use in the clinic.
Our ultimate goal is to design synthetic factors that can convert any cell in the body to a specific cell type of interest. We aim to learn from how the naturally occurring reprogramming factors interact with the genome and other molecules in the cell to change cell types.
We are particularly interested in how the reprogramming factors Oct4, Sox2, Klf4, and c-Myc (OSKM) convert fibroblasts to iPS cells. We found that the OSKM factors interact with genome in fibroblasts differently from that in ES cells. We also found that OSKM are initially blocked from accessing large chunks of the fibroblast genome, which are needed for complete reprogramming. Based on these abilities and limitations of the OSKM factors, we are currently establishing new approaches to produce custom-made reprogramming factors in the lab.