Young-Goo Han Lab

Our group has created a transgenic mouse model that maintains activated SHH signaling in the brain. We have observed a significant increase in the presence and proliferation of oRG cells, in addition to emergence of folding or gyration (a feature not witnessed in murine species). We are focused on understanding the cellular and molecular mechanisms of oRG expansion as mediated by SHH signaling. Using RNA-Seq to analyze the transcriptomes of mutant mice compared to controls, we have identified both known and novel putative regulators. Further work will validate and define the specific roles of these factors in oRG expansion. In order to assess the role of candidates in human brain development, we utilize cerebral organoid systems derived from human pluripotent stem cells, as well as ferret models which naturally feature brain folding. 

Pediatric brain tumors are considered developmental, as they often arise from progenitor cells that have escaped normal proliferation control mechanisms. Each of the different types of pediatric brain tumors are thought to arise from specific types of neural progenitor cells. We hypothesize that oRG cells, which are vastly abundant in developing human brains, are cells of origin for certain pediatric high-grade gliomas. Conventional mouse models have few oRG cells which are necessary to interrogate molecular mechanisms, and so we are leveraging our SHH-model to decipher pathogenesis. Additionally, we are exploring the role of the primary cilium, the cellular antenna, as a factor in tumorigenesis. Our group has discovered that primary cilia have opposing roles depending on their presence or absence in a given tumor. In tumors with these structures, primary cilia seem to promote tumorigenesis, while in those without them, they serve to inhibit tumor development. At St. Jude, we have access to a complete database of human tissue samples that enables us to evaluate the connections between primary cilia and tumor subgroup.