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A Developmental Model to Characterize the Epigenetic Origins of the Retinoblastoma Tumor Initiating Cell

The Johns Hopkins University School of Medicine
Jeffrey Huo, MD, PhD
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 

Dr. Huo has moved to Levine Children's Hospital in Charlotte, NC


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 Goal

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.

Project Update 2016

Thanks to the support of the ALSF, the laboratory of my mentor (Dr. Elias Zambidis) and I have helped make significant advances towards the use of adult pluripotent stem cells to model pediatric cancer. Towards the goal of modelling the earliest stages of retinoblastoma development, ALSF support has helped us generate next-generation naïve pluripotent stem cells without the use of transgenes or anti-apoptosis inhibitors that would interfere with cancer modelling. ALSF support has also enabled me to help advance clinical research into advancements in bone marrow transplantation and immunotherapy, an important part of the treatment of some retinoblastoma patients.

* Click here to watch a video about Dr. Huo’s work.

* Read more about Dr. Huo and one of his patients here.

"Studying the very earliest stages of retinoblastoma formation in babies is very difficult, yet key to developing new drugs for eradicating this devastating pediatric tumor. Our novel approach will be to use novel human stem cell engineering tools to recreate the earliest stages of malignant retinal genesis in a dish. Thanks to the ALSF, we now have the chance to pursue this developmental disease model, and use it to identify the cancer stem cells that may actually give rise to retinoblastoma." ~Jeffrey Huo, MD/PhD

Co-funded by: 
Northwestern Mutual Foundation