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American Liver Foundation
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New York, New York 10006
American Liver Foundation Postdoctoral Research Fellowship Award
Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts
“Role of nitric oxide signaling in liver development and regeneration in zebrafish”
Liver disease is a common cause of morbidity and mortality. Elucidating the key pathways involved in liver development is essential for our knowledge of normal liver function and the maintenance of tissue homeostasis. Disturbances in liver development can lead to severe malformation of the hepatobiliary system, whereas unregulated growth can lead to hepatic neoplasia. In order to identify novel regulators of liver development in vivo, a chemical genetic screen was performed in zebrafish (Danio rerio) using a library of over 2,500 compounds with known biological activity. This screen revealed that compounds impacting on nitric oxide (NO) signaling modulated liver development. Although the function of NO on the vasculature is well established, the role of NO on endoderm development is largely unknown. Dr. Cox will use chemical manipulation, complemented with gene knockdown and rescue experiments to characterize the effect of NO signaling on liver development and elucidate downstream signaling pathways. He will then determine whether NO signaling enhances regeneration using recently established surgical and chemical models of liver injury. The information revealed by these studies will enhance our understanding of the signaling networks regulating liver growth, and will help to identify therapeutic targets to improve liver regeneration and combat hepatic neoplasia. A Postdoctoral Research Fellowship Award from the American Liver Foundation will allow Dr. Cox to work in the highly stimulating and supportive environment at Brigham and Women’s Hospital to elucidate the mechanism by which NO signaling regulates liver formation and regeneration in zebrafish.