Kam W Leong
Direct cellular reprogramming, or transdifferentiation, where adult cells are converted from one lineage to another lineage without going through an intermediate stem cell-like stage, represents the next frontier of regenerative medicine or tissue engineering. An example would be the direct conversion of adult cells such as fibroblasts or endothelial cells into functional neurons.
Neurodegenerative diseases are responsible for an enormous proportion of global morbidity and mortality. There are currently no effective treatment options. Neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease are characterized by extensive cell death: loss of neurons in the neocortex and hippocampus in the case of Alzheimer’s and loss of dopaminergic (DA) neurons in the substantia nigra in the case of Parkinson’s. Cell replacement therapy is an attractive long-term alternative to pharmacologic intervention or deep brain electrical stimulation. However, procurement of the appropriate cells for therapy has long been a challenge. Embryonic stem cells (ESC) can be differentiated into functional neurons but safety and ethical issues are significant barriers. Induced pluripotent stem cells (iPSC) can sidestep the ethical issues but the risk of teratoma formation persists. The generation of a safe source of autologous human neurons, by direct cellular reprogramming, would represent a transformative cell therapy against intractable neurodegenerative diseases.
So far all the success on direct cellular reprogramming has mostly been achieved by viral delivery. We focus on nonviral delivery approach to facilitate clinical translation. The overall objective of our research program is to systematically investigate and optimize the biochemical and physical cues dictating direct cellular reprogramming. In particular we will do so by leveraging on biomaterials and biomedical engineering techniques and innovations.