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Home > Education Resources > Liver Lowdown > Liver Lowdown July/Aug 2015 > Researcher

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Zenobia Cofer, PhD, Children's Hospital of Philadelphia

Recipient of:

Dean Thiel Memorial Postdoctoral Research Fellowship


Epigenetic Regulation of Hedgehog signaling in biliary atresia disease progression and development

Mentor: Randolph Matthews, MD, PhD

Dr. Zenobia Cofer was in the laboratory-- working with her zebrafish colony--when she learned that she had received a 2014 Research Award from the ALF. “It was an ecstatic moment for me,” Zenobia said – a chance to do independent research on an important and original idea.

Zenobia is using the zebrafish to study Biliary Atresia (BA), a disease of the bile ducts that affects only infants. In BA the bile ducts become inflamed and blocked, causing bile to remain in the liver, where it causes cirrhosis or scarring of the liver. There is no cure for BA; some babies with the condition may benefit from a surgical procedure; all will need specialized care, and in some cases a liver transplant.

Zenobia approached the study of BA from a background in genetics. She chose the zebrafish for her model, because it turns out that this small minnow-like fish is a powerful tool for the study of liver diseases that affect children. Zenobia works with the zebrafish larvae; the liver system is complex and develops in only a few days after fertilization. That means that she can quickly look at how liver development changes when genetic pathways are disrupted or inhibited--when larvae are given a drug, for example.

Zenobia’s research focuses on chemical markers, called methylation, that are present on certain regions of DNA as a way to help turn on and off and gene expression. When DNA loses methylation marks, gene expression can turn on, leading to improper activity. Using zebrafish as a model, Zenobia is looking at how liver development changes when there are problems with DNA methylation. She has found that that the loss of methylation increases the expression of Hedgehog gene activity in BA; and that zebrafish larvae that have lower DNA methylation also have liver defects. But when larvae are given a drug that blocks Hedgehog gene expression, their livers have a normal appearance. This important finding suggests that BA may be caused by a loss of DNA methylation leading to higher Hedgehog gene expression. If this is true, then drugs targeting Hedgehog gene expression may in the future be used in the treatment of BA.

For her work, Zenobia received the Presidential Award at the 65th Annual Meeting of the American Association for the Study of Liver Diseases. She is excited about the research funded by her ALF grant, and grateful for the opportunities to network with leading researchers through AASLD. A native of Philadelphia, she is just as proud of her work as a volunteer in science education for low-income minority-students in the community.

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Page updated: August 4th, 2015


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