Aging and Rejuvenation
Aging, characterized by the functional decline of tissues and organs, is a major risk factor for most diseases affecting modern societies, including cancer, cardiovascular and neurodegenerative diseases. Several rejuvenation strategies have been proposed to delay ageing and the onset of age-associated decline and disease to extend healthspan and lifespan. Our laboratory is trying to advance and further develop some of these strategies including metabolic manipulation, partial reprogramming, senescent cell reprogramming and ablation, and endogenous tissue and organ regeneration. A major focus in our research activities is to study the association of aging with altered epigenetics mechanisms of gene expression, which we consider central to the effectiveness of age-delaying interventions.
Stem cells and Developmental Biology
Pluripotent stem cells—which can be turned into any cell type in the body—hold promise for treating diseases ranging from Alzheimer’s, to heart, liver diseases or blindness. These cells can be harvested from embryos or they can be reprogrammed from somatic cells. In our lab, we are trying to understand the molecular pathways involved during embryonic development with the goal of repurposing them in cells within a living organism, to induce cell plasticity and regenerate organs and tissues in a targeted manner. We are also trying to generate tissues and organs in vivo that ultimately might be used in for transplantation.
Genomic and Epigenetic Editing
Genome-editing systems are tools designed to insert, delete, modify or replace DNA sequences. In our lab, we are developing technologies to improve gene editing systems by increasing their efficiency, specifity and minimizing off target effects Additionally, we are also exploring the modification of the epigenome as a way to understand and modify phenotypes. For instance, we recently repurposed the CRISPR/Cas9 system to enable targeted gene activation (TGA), allowing modulation of endogenous gene expression without inducing DNA damage to treat mouse models of diabetes, muscular dystrophy, and acute kidney disease. Another example is the insertion of CpG-free DNA into targeted CpG islands (CGIs), inducing de novo methylation. These studies might be helpful to determine whether DNA methylation marks can be passed on to the next generation, a phenomenon with large implications in heredity disease and organismal evolution. Overall, the combination of gene and epigenome-editing technologies alongside the use of stem cells for transplantation represents an attractive alternative to current approaches for human disease treatment.