Akizu Lab Research Overview

Through collaborations with clinical geneticists worldwide, our lab is at the forefront of identifying genetic causes that inform novel diagnoses and treatments for neurodevelopmental disorders including autism and intellectual disabilities. Although these disorders are highly heritable, the underlying causes are often complex and include gene and environment interactions that we continuously survey in the lab.

Variants in genes encoding chromatin regulators are recurrently associated with neurodevelopmental disorders. Focused on the polycomb repressive complex 2, a chromatin regulatory complex involved in the epigenetic transmission of cellular identity, our work aims to uncover how diverse chromatin machineries cooperate to determine neuronal subtypes during brain development and how their disruption causes disease.

The developing human brain is exquisitely sensitive to metabolic dysregulation. Our work aims to unlock how metabolic enzyme polymerization protects neurons from degeneration and why the cerebellum is selectively vulnerable to lipid and lysosome homeostatic defects. This research is founded on two childhood neurodegenerative disorders of the posterior brain that we genetically defined.

Despite evidence demonstrating that neurodevelopmental disorders are treatable, successful treatments are still scarce. Leveraging our mechanistic studies, we aim to develop innovative strategies to treat these disorders. In collaboration with the Goldberg Lab at the Children’s Hospital of Philadelphia, we contributed to their efforts in unraveling a targeted therapy that improves seizures and motor behavioral defects in an animal model of progressive myoclonus epilepsy. We are also developing novel epigenetic treatments for neurodevelopmental disorders.