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Valerie Castle, M.D.

Ravitz Professor and Chair, Department of Pediatric and Communicable Diseases Pediatrician-in-Chief

Director of the Taubman Institute's Neuroblastoma Research Program

Discovering Treatments for Childhood Cancers

When Valerie Castle began her career as a pediatrician in the early 1980s, the survival rate for acute lymphoblastic leukemia had gone from near zero in the 1930s and 1940s to almost 50 percent. Today, survival rates exceed 85 percent. Great gains such as these in survival rates for children with cancer have occurred because of the persevering work of physician-scientists like Castle who have teamed together — at C.S. Mott Children’s Hospital and in networks with researchers around the world — to treat children collaboratively and with ever-increasing and far-reaching effectiveness.

Castle’s research focuses exclusively on the pediatric solid tumor, neuroblastoma. She is specifically interested in mechanisms of chemotherapy and radiation resistance as well as studies on the control of neuroblastoma invasion and metastases. Her latest studies have been in the area of chromosomal rearrangements, a hallmark of cancers including neuroblastoma. These can be caused by incorrect DNA repair. Castle’s laboratory has recently discovered that the levels of proteins involved in the repair of damaged DNA are abnormally high in neuroblastoma tumors, and these levels correlated with a shorter duration of patient survival, suggesting that defective DNA repair resulting in chromosomal abnormalities may contribute to the poor outcome or even the development of this disease.

Using the facilities of the Taubman Institute’s Consortium for Stem Cell Therapies, Castle is now developing a neural crest stem cell model of this neuroblastoma. She is testing the hypothesis that overly active DNA repair during development of the neural crest stem cell into a nerve cell is a fundamental step in the development of neuroblastoma tumors. After differentiating an established human embryonic stem cell line into a neural crest stem cell, her investigators will express the DNA repair factors they believe are critical in the development of this tumor. These genetically modified lines will then be analyzed for their similarities and differences to human neuroblastoma cancer cell lines that have been established in the Castle laboratory. This groundbreaking work has the potential to uncover the underlying mechanisms in the development of this devastating cancer in children.

Research Findings:

• Progress Report, May 2010 (PDF, 150KB)
• HDAC6 Deacetylates Ku70 and Regulates Ku70-Bax Binding in Neuroblastoma (PDF, 1.7MB)

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