Our final goal is to understand and harness the regenerative potential within our own cells and organs for therapy.
During development, an exquisitely orchestrated series of biological processes lay down the map for the entirety of our bodies, and carry it out to perfection. Thus, the information and capacity to recreate every single one of our organs and tissues is contained within ourselves. However, after birth we slowly lose this ability for a variety of reasons (aging, stem cell depletion, oxidative stress, among others). In some organs, that capacity never manifests during adult life and is insufficient to bring any functional improvement in case of damage (e.g. heart, brain). In other organs, it is maintained throughout life (e.g. gut, liver), although this seems to be the exception rather than the rule in humans. This does not stop the human gut epithelium from regenerating the equivalent to the surface of a tennis court every five days! Our poor regenerative capacity is at the core of many pathologies as we age, but what would happen if we could reactivate it once more, in a controlled fashion, with therapy in mind?
For that purpose, we can look at examples in nature. Unlike humans, many vertebrates exhibit a remarkable capacity to regenerate, including mammals (mice), amphibians (newt) and fish (zebrafish). In cases where regeneration occurs, it happens either by mobilizing endogenous stem cell pools (e.g. satellite cells in skeletal muscle) or by dedifferentiation of tissue resident cells (the best characterized model in mammals being cardiomyocytes in the heart) with no detectable downside effects and complete functional restoration. The molecular events behind these processes are complex, involve a multitude of cells types and signals, and overall are very poorly understood. However, their study can offer valuable clues about regeneration in humans and help us develop bio-inspired reprogramming therapies to treat a vast array of diseases, including cardiovascular disorders, our main topics of interest.
We currently work on three main lines or research:
Lipids and metabolism. Investigating how the cell's metabolism (in particular lipids) is involved in the processes or regeneration, cell reprogramming, injury and disease. Development and regeneration. Understanding how the body map is laid out (development) and remodeled as an adult organism, as it offers insights into competent states, differentiation (programming) and dedifferentiation (reprogramming). Our most common systems are the zebrafish and mouse.
Bio-inspired reprogramming. Applying bio-inspired reprogramming and synthetic biology approaches to developing ground-breaking regenerative therapies, either by 1) reprogramming somatic cells to become stem cells with healing properties 2) Expanding or activating resident stem cells or 3) by remodeling their environment to facilitate regenerative states.
To tackle these questions, we use an ample array of techniques, including mass spectrometry-based lipidomics, molecular and cellular biology, functional genomics, CRISPR/Cas9 genome manipulation, high-content screenings, human pluripotent stem cells, organoid systems and animal models (mouse and zebrafish).