Nodal Signaling Promotes Retinoblastoma Invasion and Growth
Retinoblastoma represents about 3% of all pediatric cancers and is the most common childhood intraocular malignancy. It is fatal if untreated, with earlier diagnosis leading to better results. The most severe problem today relating to retinoblastoma is metastasis, which is the invasion and spread of cancer cells outside the eye. Metastatic retinoblastoma has the ability to spread from the retina to the Central Nervous System (CNS), bone or other organs through the optic nerve or blood. Chemotherapy is largely ineffective against metastatic retinoblastoma, creating a need for new therapeutic targets. The Eberhart group has found that the ALK7 receptor, an important component of "Nodal" signaling, was induced at least two-fold in invasive tumors, and we are following up on the role of this receptor and pathway in retinoblastoma.
The hypothesis is that pharmacological or genetic inhibition of the Nodal signaling will reduce invasion, proliferation and growth of retinoblastoma cells. This will be tested using drugs that inhibit downstream proteins, as well as genetic inhibition of the ALK7 receptor using shRNA technology. Multiple retinoblastoma cell lines will be treated with varying concentrations of the drug and different variations of the shRNA, and then the invasion, apoptosis (or cell death), and proliferation of the cells will be tested using different assays. I will also have the opportunity to observe how inhibition of the pathway affects the growth and spread of retinoblastoma cells in the eyes of fish, although I will not directly take part in these experiments.
Mentored by Dr. Charles Eberhart
Johns Hopkins University School of Medicine, Baltimore, MD