Tristan Rodriguez joined the Heart Science section of the National Heart and Lung Institute (NHLI) in October 2011.
Tristan Rodríguez trained as an embryologist in the laboratory of the late Dr. Rosa Beddington (National Institute for Medical Research, London, Mill Hill), who was a key figure in establishing the early mouse embryo as a model system to understand cell fate. In 2002 he was awarded a Lister Institute of Medicine non-clinical fellowship to work on axis specification in the mouse embryo and moved to the MRC Clinical Sciences Centre to initiate this work. During this period his research focussed on studying the signalling centres and signals that pattern the early mammalian embryo. At the end of 2011 the Rodriguez laboratory moved to NHLI recruited into the Heart Science section by Professor Michael Schneider as part of a new cardiovascular initiative and in 2012 Tristan was awarded a 5-year lectureship. Here his group is focussed on understanding the first steps of embryonic stem cell differentiation.
This research focuses on understanding the mechanisms that control cell fate decisions and cell survival in the early mammalian embryo. The main models used for these studies are genetically manipulated embryos and embryonic stem cells. Specifically, the Rodriguez group studies how cells exit the pluripotent state and initiate the differentiation program to form the three definitive germ layers that will give rise to the precursors of all the tissues and organs of the fetus: the endoderm, mesoderm and ectoderm. This research involves analysing the signalling pathways, transcriptional events, cellular metabolic pathways and epigenetic mechanisms that regulate germ layer differentiation. By integrating this information into the context of the developing embryo we hope to achieve an understanding of how multiple cellular and molecular inputs are coordinated during the differentiation process and to apply the knowledge we obtain to regenerative medicine.
A key finding of the group involved identification of cell competition as a novel mechanism that monitors cellular fitness during early embryonic development. This work allowed the group to identify that at the onset of differentiation embryonic stem cells monitor their relative fitness and that those cells with mutations that adversely affect their signalling, growth rate or metabolic activity are eliminated before they have adverse effects for the development of the embryo.
Another important contribution of the group has been to unravel the key role that microRNAs play in the maintenance of the different pluripotent stem cell populations of the early embryo. This work allowed identification of the key miRNA-mRNA interactions that control multipotency and cell survival during early embryonic development.
et al., 2015, Activin A directs striatal projection neuron differentiation of human pluripotent stem cells, Development, Vol:142, ISSN:0950-1991, Pages:1375-1386
et al., 2018, The Mitochondria and the Regulation of Cell Fitness During Early Mammalian Development, Current Topics in Developmental Biology, Vol:128, ISSN:0070-2153, Pages:339-363
et al., 2018, P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development, Nature Communications, Vol:9, ISSN:2041-1723
Di Gregorio A, Bowling S, Rodriguez TA, 2016, Cell Competition and Its Role in the Regulation of Cell Fitness from Development to Cancer, Developmental Cell, Vol:38, ISSN:1534-5807, Pages:621-634
et al., 2014, HOIP Deficiency Causes Embryonic Lethality by Aberrant TNFR1-Mediated Endothelial Cell Death, Cell Reports, Vol:9, ISSN:2211-1247, Pages:153-165
et al., 2014, MicroRNAs control the apoptotic threshold in primed Pluripotent stem cells through regulation of BIM, Genes & Development, Vol:28, ISSN:0890-9369, Pages:1873-1878
et al., 2013, Competitive Interactions Eliminate Unfit Embryonic Stem Cells at the Onset of Differentiation, Developmental Cell, Vol:26, ISSN:1534-5807, Pages:19-30
et al., 2012, Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors, Nature Communications, Vol:3, ISSN:2041-1723
et al., 2011, Crosstalk between Nodal/Activin and MAPK p38 Signaling Is Essential for Anterior-Posterior Axis Specification, Current Biology, Vol:21, ISSN:0960-9822, Pages:1289-1295
et al., 2010, An Early Developmental Role for miRNAs in the Maintenance of Extraembryonic Stem Cells in the Mouse Embryo, Developmental Cell, Vol:19, ISSN:1534-5807, Pages:207-219
et al., 2011, Coordination of cell proliferation and anterior-posterior axis establishment in the mouse embryo, Development, Vol:138, ISSN:0950-1991, Pages:1521-1530