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The role of vitamin D in hepatoblastoma formation and prevention

Institution: 
Brigham and Women's Hospital
Researcher(s): 
Wolfram Goessling, MD/PhD
Grant Type: 
Innovation Grants
Year Awarded: 
2012
Type of Childhood Cancer: 
Hepatoblastoma
Project Description: 

Hepatoblastoma is the most common liver cancer of infancy and early childhood, that has become much more common in recent years. The tumor often requires aggressive chemotherapy and liver transplantation. Hepatoblastomas originate from primitive liver cells, so-called liver stem cells, that are formed during embryonic development. This means that the embryonic period prior to birth holds the key to our understanding of the development and prevention of hepatoblastoma. In our laboratory, we are using zebrafish to investigate the role of biological signals that affect liver formation during embryonic development. We discovered that vitamin D regulates liver growth during development and may affect liver stem cells during this period. This gives us reason to believe that lack of vitamin D may contribute to the formation of liver cancer in children. In fact, just like lack of a gene can cause cells to growth uncontrolled, we propose that lack of vitamin D can lead to changes in the architecture of the DNA that leads to cancer. We will use the zebrafish, as well as cancer cells in the petri dish and patient tumor samples, to identify how vitamin D impacts liver stem cells and liver growth and ultimately hepatoblastoma formation. We hypothesize that sufficient vitamin D levels are important to regulate liver growth and prevent hepatoblastoma formation. Our findings may lead to direct recommendations regarding vitamin D supplementation in pregnant women and may offer additional strategies to treat the tumor in those children where surgery alone is not enough.