Research Projects

Cell cycle machinery plays a crucial role in proper development, and anomalies can lead to developmental disorders or cancers. Neurodevelopmental disorders, such as Autosomal Primary Recessive Microcephaly (MCPH), result from reduced cell division, while neurodegenerative disorders occur in adults due to lack of protein turnover, leading to loss of neuronal function and death. Studying genes in neurodevelopmental hotspots like the 19q13.2-13.2 locus simultaneously will provide a comprehensive understanding of their physiological roles in brain development. The 19q13.2-13.2 locus contains the highest density of zinc finger transcription factors (ZNFs), with C2H2 ZNFs being particularly enriched. However, their roles and regulation during human brain development and in cancers are poorly understood. These ZNFs have evolved in a lineage and species-specific manner in humans and mammals, leading to duplication of genes and loss of certain effectors and proteins. Delineating the roles of these ZNFs is essential to understand their species and lineage-specific functions. This proposal aims to study the roles of ZNFs in human brain development using mini human brain organoids using a loss of function approach. The locus is implicated in glioma, and the study will investigate their possible role in gliomagenesis using cancer stem cells, spheroids, and glioblastoma organoids. The study will prioritize genes based on expression in lower versus higher grade glioblastoma and developmental stages in the human brain.