Stephen A. Duncan, DPhil

Professor and Chair
Department: Regenerative Medicine & Cell Biology
Programs: Cell Injury, End Organ Disease
Cell Models Core

 

 

Research Interests:

The liver has vital endocrine and exocrine functions that regulate a diverse array of metabolic activities. Although specific forms of inborn errors of hepatic metabolism are relatively rare, cumulatively they are common and without treatment are often fatal. To date, a liver transplant can treat the most severe hepatic metabolic deficiencies. Unfortunately, the number of available donor livers is limited, and demand for transplant-quality livers continues to increase. With donor livers being scarce, it has been proposed that cell transplant therapy may offer an alternative to organ transplant. One source of hepatocytes for transplant could be human induced pluripotent stem cells (iPSCs). Several projects in Dr. Duncan’s laboratory, therefore, focus on generating functional hepatocytes from iPSCs.

Metabolic liver disease can also often be treated using small molecules or biologics that, in general, have an established track record of success. With this in mind, Dr. Duncan and his team are developing a platform that will facilitate the efficient identification of treatments for rare inborn errors of hepatic metabolism. They propose to 1) establish human pluripotent stem cells harboring genetic variants associated with liver disease in patients, 2) differentiate the stem cells to hepatocytes and examine whether genetic variations recapitulate the disease in culture, 3) establish assays that are compatible with moderate to high throughput screening to identify existing drugs that could be repurposed to correct the pathophysiology of the disease, and 4) establish the efficacy and safety of lead drugs using humanized animal models and human trials.

Publications:

PubMed Collection