A Developmental Model to Characterize the Epigenetic Origins of the Retinoblastoma Tumor Initiating Cell
Dr. Huo has moved to Levine Children's Hospital in Charlotte, NC
Background
The first tumor suppressor gene discovered was RB1. Loss of RB1 gene function can lead to many cancers, but the one that appears earliest is retinoblastoma in infants. Unfortunately, retinoblastoma treatment is highly toxic and can cause affected babies to lose one or both eyes. If we understood how loss of RB1 caused cancer to arise during the growth of the baby retina, we could develop more effective, less toxic cures for retinoblastoma. Understanding how loss of RB1 causes retinoblastoma would also help us understand how RB1 loss contributes to other, later cancers, like osteosarcoma.
Project Goals
In this project, we will establish the first model in a dish of how RB1 leads to retinoblastoma in the baby eye. Our group of laboratories recently discovered how to start with adult blood, turn it into adult stem cells, and then grow those adult stem cells into retina-like cups in a dish that behave like real retinas. We will take these adult stem cells, knock out RB1 gene function (just like what is seen in babies with retinoblastoma), watch carefully to see at what step of retina growth retinoblastoma appears, and identify what kind of retina cells retinoblastoma comes from. We will then dissect the patterns of genes, miRNAs, and DNA methylation marks that are abnormal in the retinoblastoma-causing cells. These patterns will help us learn what pathways triggered by loss of RB1 help cause retinoblastoma and other cancers, and help us develop new drugs targeting those pathways.
