Based on our recent expertise (Garcia-Gonzalez et al., 2025 Nature Methods and Garcia-Gonzalez et al., 2024 NAR), we aim to develop novel RNA/DNA- and protein-based single-cell and spatial barcoding tools. This will involve advanced genetic engineering technologies, using CRISPR-Cas9-assisted genome targeting of very large and expressible DNA elements. Once these novel tools are established, we aim to simultaneously target gene function and track, over long periods, how single-cell lineages with differing gene activity change their proliferation, migration, survival, or differentiation state in a developing living organism or disease conditions. This powerful approach will provide all-in-one spatial and temporal resolution of any mutant or wild-type single-cell-derived lineage.
In the future, one of our lab’s main projects will be to use these new multispectral and DNA/RNA barcoding technologies to characterize the biology and spatial heterogeneity of single cardiovascular progenitors in adult organ homeostasis and disease. We will map how single vascular (and adjacent non-vascular) cells communicate, clonally expand, differentiate, migrate, or die over time within the tissue, and identify which genes are most important and can significantly change their biology when targeted. This will provide exciting insights into the spatial heterogeneity of vascular cells, their niches, and how their collective and social behavior changes after specific genetic or pharmacological interventions.
Another aim of these novel technologies will be to model and quantify at very high spatiotemporal resolution how particular combinations of genetic mutations influence the initiation and development of cancer from single mutant cells.