Research Areas
Spatial Chromatin Organization in Intellectual Disabilities
Intellectual disabilities associated with genomic imbalance (aneuploidies or large copy number variants) display abnormal brain morphogenesis and deficits in learning and memory. Our studies have uncovered that genomic imbalance disrupts the 3D-genome organization, epigenome and transcriptome of neural progenitors, the multipotent stem cells of the developing brain that differentiate into neurons and glia. Additionally, we found that dynamic spatial chromatin reorganization plays a critical role in memory formation, consolidation and recall, however, how large structural variations impact these processes remains unknown. To address this knowledge gap, we aim to understand how genomic imbalance impacts global chromatin organization in specific brain cell types to manifest in abnormal neurodevelopment and deficits in learning and memory.
Senescence in Neurodevelopmental Disorders
Cellular senescence is a stress response that impairs the proliferative capacity of cells and is typically associated with aging, however, studies have revealed that senescent cells exist in a transient state during development. Our studies utilizing stem cells derived from individuals with Down syndrome revealed that genomic imbalance induces neural progenitor senescence. Building on these findings, we hypothesize that genomic imbalance induced senescence leads to abnormal morphogenesis and altered cellular composition of the brain. We are interested in understanding the cell type-specific contributions of genomic imbalance induced senescence on the neurodevelopmental and cognitive deficits associated with intellectual disabilities.
Neuro-Glial Interplay in Intellectual Disabilities
The importance of glial cell types, including astrocytes, oligodendrocytes, and microglia, in brain development and disease is becoming increasingly apparent. Despite this, we still lack a mechanistic understanding of the dysfunctional interplay between neurons and glial cells in neurodevelopmental disorders. We aim to characterize how genomic imbalance alters the synergistic relationship between neurons and glial cells to gain insight into the pathogenesis of intellectual disability disorders.
Scientific Approach
Human Stem Cell-Derived 2D and 3D models of the brain
Human Stem Cell-Derived 2D and 3D models of the brain
Mouse Models
Human Stem Cell-Derived 2D and 3D models of the brain
