The pancreas is essential for normal digestion and maintenance of blood sugar levels. The Gannon Lab studies the role of genes and signaling pathways involved in the development and function of specific cell types within the pancreas.

The HNF6 transcription factor is expressed in all pancreas cells early in embryonic development, but is "turned off" in islet cells just before birth in the mouse. Dr. Gannon's lab developed mice in which HNF6 is over-expressed or can be inactivated conditionally. These studies reveal that HNF6 is essential to generate the appropriate number of endocrine progenitor cells, but that it must get "turned off" in order for the insulin-producing cells to function properly. Current studies are examining how HNF6 interacts with other factors in the embryonic pancreas to regulate endocrine differentiation. Gannon lab studies also revealed that HNF6 is essential for normal growth and branching of the pancreatic ductal epithelium. In the absence of HNF6, pancreatic duct differentiation is impaired and the mice develop pancreatitis.

A second project in the Gannon lab examines the role of CTGF, a secreted factor known to modulate growth factor signaling and affect cell proliferation and migration in other organ systems. Lab members found that loss of CTGF results in decreased embryonic islet beta cell proliferation and defective islet formation. They are using conditional gene inactivation and over-expression strategies to determine how CTGF affects islet development and function during embryogenesis and after transplantation.  

Finally, the FoxM1 transcription factor is highly expressed in proliferating cells and is essential for normal cell division. Dr. Gannon's lab has generated mice specifically lacking FoxM1 in the pancreas. In these mice, the number of insulin-producing cells fails to increase with body mass, resulting in diabetes. Significantly, they found that FoxM1 is required downstream of all proliferative stimuli in the insulin-producing beta cells. For example, the number of beta cells expands via mitosis when animals are fed a high fat diet, or during pregnancy. In FoxM1 mutants, this increase in mitosis does not occur and the animals become diabetic.

The Gannon lab's current studies are aimed at characterizing the signaling pathways that activate FoxM1 expression and activity as well as identifying target genes of FoxM1 in the insulin-producing cells.

NEWEST PUBLICATIONS

Genetic interactions between hepatocyte nuclear factor-6 and notch signaling regulate mouse intrahepatic bile duct development in vivo.
2012 Hepatology 55: 233-243

Connective tissue growth factor acts within both endothelial cells and beta cells to promote proliferation of developing beta cells.
2011 PNAS USA 108: 15242-15247

Type 2 diabetes and the aging pancreatic beta cell.
2011 Aging 3: 565-575