Frederic Lluis performed his PhD studies at the Centre de Regulació Genómica (CRG) (Barcelona, Spain) in the group of Dr. Pura Muñoz-Canoves between 1999 and 2004. In October 2005, he joined Dr. Pia Cosma’s group as a postdoctoral fellow at TIGEM (Naples, Italy). Since 2010 he is a staff scientist in her group at CRG (Center of Genomic Regulation), Barcelona, Spain. In February 2011, he has been awarded the Miguel Servet contract from the Carlos III program.
Lluis investigates the role of the Wnt/beta-catenin pathway controlling reprogramming of somatic cells with the final goal being to determine the protein interactors and targets of the Wnt pathway that contribute to this reprogramming.
Differentiation from zygotes has been considered a unidirectional route in all cells of the body. Recently, however, it has become clear that the reverse path is also possible: the reprogramming of somatic nuclei, i.e. the de-differentiation of somatic cells into pluripotent stem cell-like cells. To date, reprogramming has been induced in vitro by transferring somatic nuclei into enucleated oocytes, by fusing embryonic stem cells (ESCs) with somatic cells, and by transferring specific factors into different types of somatic cells.
Signalling pathways participate in almost all cellular processes. We have recently shown that activation of the Wnt/β-catenin signalling pathway enhances reprogramming of somatic cells after their fusion with ESCs. Furthermore, recently it has been also shown that modulation of other signalling pathways as MAPK/ERK and PI3K/Akt signalling pathways strikingly enhances reprogramming efficiency. Despite these important findings, the molecular mechanisms driving reprogramming are still largely unknown, and moreover, the downstream molecular interactors and the target genes that regulate this process are unclear.
Wnt signalling and the reprogramming of cell fate to pluripotency
Spontaneous cell fusion between two cells of different lineages can originate new hybrid cells that have different features from the original parent cells. If one of the fusing parent cells is highly plastic, such as a stem cell, and the other is a somatic cell, their fusion can be followed by reprogramming events that generate new hybrid pluripotent cells. However, whether cell-fusion-mediated reprogramming can occur in vivo in higher vertebrates, and what are the molecular mechanisms and genes that drive the reprogramming, remain to be defined. We have shown that activation of the Wnt/β-catenin signalling pathway enhances reprogramming of somatic cells after their fusion with embryonic stem cells. We are currently dissecting out the gene networks and studying the mechanisms of in-vivo somatic-cell reprogramming, to determine whether reprogrammed hybrids have the potential to differentiate and regenerate adult tissues.
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