Michael Kareta, PhD, Lab
Primary Research Focus
The research in our laboratory is to study the basic mechanisms which define cellular identity, and how identity may be altered to promote disease. In particular we are currently investigating the mechanisms that “stem cell” genes play in the formation of multiple pediatric and adult tumors. We explore these foundational questions by the use of mouse genetics, cell culture, and molecular biology techniques combined with next generation genomic and bioinformatics analysis with a long term goal of generating novel therapeutics.
Behind the Research
Our laboratory is focused on the role of pluripotency pathways in tumor formation using both genetically engineered mouse models and cellular reprogramming techniques. In particular we are investigating the role of the Sox2 gene in the formation of tumors. We have previously identified Sox2 as a downstream target of the retinoblastoma (Rb) tumor suppressor. Using induced pluripotency we observed that upon Rb loss, Sox2 is upregulated and the cells are more able to be reprogrammed to a acquire a new cellular identity. Additionally we observe that this upregulation of Sox2 is required in the formation of tumors following Rb loss. As the mechanism by which Rb loss promotes tumors is not fully understood, understanding the downstream networks activated by Rb loss will be critical for the development of future therapeutics. Therefore we will continue our study into Sox2 oncogene function using multiple genomic and cutting-edge bioinformatics approaches so that we may shed light on foundational networks in cancer and validate new targets to inhibit in the clinic.Resident Sox2+ cells are the cell of origin for neuroendocrine tumors