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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.

The Weimer Lab focuses on understanding mechanisms of polarized signaling involved in development of the cerebral cortex. These processes are known to regulate the proliferation and placement of neurons, formation of axons in differentiating cells and long term maintenance and trafficking within these same processes.

The Weimer Lab draws on expertise in cell and molecular biology, genetics and behavioral neuroscience to answer questions that bridge from basic mechanisms to translational and clinical approaches to treat human disease. These questions answer how and why various scaffolding or “signaling complex” form in neurons, how disruption in these complexes can contribute to human disease and determine if these complexes may serve as druggable targets.

Specifically, the team explores a number of mechanisms involved in neural stem cell proliferation, neuronal polarity and axonal outgrowth and trafficking with the hope of advancing our knowledge of neurobiology and aiding in the future treatment of rare neural developmental disorders. This includes projects focused on neuropediatric disorders including Batten disease, cortical malformations and neurofibromatosis type I.

Research in the Pilaz Lab focuses on cellular and molecular mechanisms regulating the production, migration and survival of neurons in the context of brain development in health and disease. We love to develop new tools to give researchers the means to push the limits of knowledge. When it comes to brain development, our go-to method is in utero electroporation, allowing us to introduce DNA, RNA and proteins, into live embryonic mouse brains. We couple in utero electroporation with CRISPR to alter the genome of neural stem cells and their progeny using a technique we developed called Breasi-CRISPR. We mainly use Breasi-CRISPR to tag endogenous proteins and visualize them within isolated cells, both live and fixed. Current efforts try to leverage Breasi CRISPR to tag mRNAs instead of proteins.