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Defining the Mechanism by which LIN28B acts as an Oncogene in Neuroblastoma

Children’s Hospital of Philadelphia
Robert Schnepp, MD, PhD
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 

Dr. Schnepp has joined the Department of Pediatrics at Emory University and is a member of the Aflac Cancer and Blood Disorders Center in Atlanta, GA.

Neuroblastoma is a childhood cancer that affects developing nerve cells called neuroblasts. When neuroblastoma spreads throughout the body, it is called high risk. Patients with high risk neuroblastoma are treated very aggressively, with chemotherapy, surgery, radiation, and other specialized treatments. However, about half of patients with high-risk disease still die of their disease. Therefore, it is of the utmost importance to better understand this disease so that we can develop more effective therapy to treat children with neuroblastoma.

Our laboratory has discovered that a protein called LIN28B is found at very high levels in neuroblastoma, particularly in neuroblastoma which has spread throughout the body.  Patients who have high levels of LIN28B in their neuroblastoma cells do not do as well as those patients who have lower amounts of this protein.

Project Goal
We have discovered that LIN28B causes cells to grow more quickly and have evidence that LIN28B works with another protein, called RAN, to cause neuroblastoma.  In this project, we would like to first determine how LIN28B causes cells to grow more quickly and whether it also causes cells to spread throughout the body. Next, we would like to determine what other proteins, in addition to RAN, work with LIN28B to cause cancer.  Finally, we would like to study how LIN28B regulates RAN and whether blocking RAN with newly developed drugs could serve as a new and effective way to treat neuroblastoma. Our ultimate goal is to better understand this disease and develop new treatments to improve cure rates.