The central directions of RPN’s laboratory are to explore the link between metabolism > transcription > alternative splicing > stem cell fate decision/ disease. This central line is explored with an approach grounded on basic biochemistry mechanisms and the emphasis on translational applications in the cell therapy area. Recently RPN´s Lab has shown that the biochemical and physical modulation of chromatin structure can constitute a powerful tool to change transcription and gene expression. Using a simple biochemistry cue, the extracellular osmotic pressure, it it possible to change chromatin structure and transcription. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. This constitutes an alternative route to manipulate cell fate decisions. This technology has been tested in model protocols of induced pluripotency and transdifferentiation in cells growing in suspension and adherent to substrates, CD34+ umbilical-cord-blood (UCB), fibroblasts and B-cells, with increased efficiency. Also, when cells are cultured on low-rigidity substrates, show open chromatin nuclear regions and enhanced expression of endogenous pluripotency-related genes facilitating the induction of pluripotency. The group has expertise in the synthesis and delivery of nanoparticles (NPs) with different cargos in primary and stem cells and patented a light-activated NP able to release retinoic acid inside the Leukemic niche and induce the differentiation of leukemia stem cells. In this context the group is exploring the delivery of metabolic intermediates able to modulate stem cell niches and tumour microenvironments for cell therapy in cancer and regenerative medicine.
Stem Cell Metabolism
