Primary Research Focus
The ubiquitin system controls virtually all aspects of eukaryotic cell biology. This system mediates the covalent modification of proteins by the small modifier ubiquitin in a signaling cascade that involves three enzymatic steps catalyzed by E1 activating, E2 conjugating and E3 ligase enzymes. Ubiquitylation can lead to changes in protein function, localization and fate including their degradation by the 26S proteasome.
The Bustos Lab is focused on clarifying the role of the ubiquitin system in neurodevelopmental disorders with intellectual disabilities. These disorders have devastating effects on patients, their families and health systems. They also constitute a serious unsolved biomedical problem since the molecular mechanisms involved in their genesis are poorly understood and are key to developing effective therapies. Using pluripotent stem cells as a developmental model, our objective is to improve our understanding of the ubiquitylation-related molecular mechanisms that are altered in these diseases.
Lab Projects and News
Neurodevelopmental DisordersIntellectual disability is a neurodevelopmental disorder affecting cognitive and adaptive functions of around 1 to 2% of the population, especially children. Currently, these disorders lack effective treatments or cures due to the poor understanding of their molecular causes. Human genetics research has revealed that components of the ubiquitin system are often mutated in inherited forms of intellectual disability. The Bustos Lab employs a combination of cutting-edge cellular and biochemical techniques to characterize the function and regulation of ubiquitin system components such as E3 ubiquitin ligases and deubiquitylases in neurodevelopment and how this is disrupted in intellectual disabilities.
Stem Cell Maintenance and Neural DifferentiationStem cells are characterized by their capacity for self-renewal and their differentiation potency to determined cell lineages. These properties propose a high promise of stem cell use for tissue regeneration in degenerative diseases but also as a powerful model to study mechanisms of development and disease. Specific components of the ubiquitin system have been shown to be key regulators of stem cell maintenance and differentiation; however, the wider role of this system in stem cell biology is yet to be determined. The Bustos Lab uses state-of-the-art techniques to face that challenge, which will be crucial to fully understand the biology of stem cells.