Stephen Duncan PhD

Biography

Stephen Duncan was born in Glasgow, Scotland, UK, and studied Molecular Biology at the University of Glasgow. He received his Ph.D./D.Phil. from Wolfson College at Oxford University in 1992 for working on the mechanisms that controlled transmission of the poxvirus, vaccinia, with Dr Geoffrey Smith. He then moved to The Rockefeller University in New York City to undertake a postdoctoral fellowship in the laboratory of Dr James Darnell where he studied transcriptional regulation of liver development. He completed his fellowship in 1996 after which he became an Assistant Professor at the Rockefeller University. He transferred to the Medical College of Wisconsin, Milwaukee in 1997, where he moved through the ranks to become the Marcus Professor in Human and Molecular Genetics in the department of Cell Biology, Neurobiology and Anatomy. In 2007 he accepted a position as the founding Director of MCW’s Program in Regenerative Medicine. In 2015 Dr. Duncan relocated to the Medical University of South Carolina in Charleston, where he is currently the Chair of the Department of Regenerative Medicine and Cell Biology. Research in the Duncan Lab focuses on the use of mice and stem cells to understand the contribution of transcription factors to embryonic development and function of the liver. His group has developed technologies to control the differentiation of pluripotent stem cells into hepatocytes. Researchers in his laboratory have exploited this system to model rare diseases in hepatic metabolism and as a platform for drug discovery.

Research Interests

The liver has vital endocrine and exocrine functions that regulate a wide 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.