Miguel Ramalho-Santos, PhD, MSc

Core

Pluripotent stem cells have the remarkable ability to give rise to all cell types of the body, and for this reason they are called pluripotent. Because of this property, pluripotent stem cells provide exciting new avenues in Regenerative Medicine. Pluripotent stem cells may allow us to understand cellular differentiation in normal and diseased states. They may also in the future be used to generate particular cell types that are needed by patients.

My lab is interested in the genetic regulation of pluripotency. We aim to answer the question of how such broad differentiation potential is maintained at the molecular level in pluripotent cells of the mammalian embryo and in pluripotent stem cells in culture. We have characterized the gene expression profiles of pluripotent cells and identified a transcriptional program that is required to maintain pluripotency. We are dissecting the transcriptional regulatory networks of pluripotency, and the open chromatin state of pluripotent cells. In parallel, we are investigating the mechanisms that underlie nuclear reprogramming of non-pluripotent cells to the pluripotent state, in particular via the generation of induced Pluripotent Stem (iPS) cells. We are also addressing the question of the in vivo significance of pluripotency and reprogramming, which our data indicate are closely associated with germline development in mammals. We use techniques such as mouse genetics and embryology, microarrays, bioinformatics, biochemistry, mouse and human pluripotent stem cell manipulation and RNA interference. Understanding the regulation of stem cell pluripotency will provide basic insights into development of the early mammalian embryo and the germline, and will inform efforts to generate patient-specific pluripotent stem cells and rationally tailor their differentiation towards cells of therapeutic interest.