Department of Medicine-Diabetes, Endocrinology, and Metabolism
Drs. Vijay Yechoor and Lawrence C.B. Chan received the award for their joint contributions to the understanding of cell fate determination and the molecular therapy of diabetes.
In a publication in Developmental Cell in 2009, Yechoor et al. found that following the introduction of a single gene, Neurogenin3, cells in the liver can take on the structure and function of the endocrine pancreas and go on to completely reverse diabetes in mice. Yechoor and Chan also uncovered a novel mechanism for the induced beta cell neogenesis. They found that transfer of a single transcription factor into an endoderm-derived lineage is sufficient to cause cell lineage switching and induce formation of neo-islets. The newly formed islets display a complete islet-specific transcription program and produce insulin in a glucose-responsive manner, stably reversing diabetes.
Yechoor and Chan further found that the newly formed periportal beta cells possess are structured similarly to pancreatic beta cells. These findings shed light on the fundamental processes of cell fate determination and reprogramming and provide a blueprint for a potential curative therapy for insulin-deficient diabetes.
Drs. Chan and Yechoor's nomination was based on the following publications:
Yechoor V, Liu V, Espiritu C, Paul A, Oka K, Kijima H, Chan L. Neurogenin3 Is Sufficient for Transdetermination of Hepatic Progenitor Cells into Neo-Islets In Vivo but Not Transdifferentiation of Hepatocytes. Developmental Cell 2009 Mar 16: 358-73.
Yechoor V, Liu V, Paul A, Lee J, Buras E, Ozer K, Samson S, Chan L. Gene Therapy with Neurogenin 3 and Betacellulin Reverses Major Metabolic Problems in Insulin-Deficient Diabetic Mice. Endocrinology 2009 150(11); 4863-73.