Maureen Anne Gannon, Ph.D.
Molecular and cell biology of pancreas development, function and regeneration
Maureen Gannon grew up in Queens, New York. She received her B.S. in Biology from Molloy College in Rockville Centre, NY and her M.S. in Biology from Adelphi University in Garden City, NY. She received her Ph.D. in Cell Biology and Anatomy from Cornell University. Her thesis project, conducted in the lab of Dr. David Bader, examined cardiac organogenesis and the formation of the chambers of the heart in the developing embryo. Dr. Gannon pursued her postdoctoral training in the laboratory of Dr. Chris Wright at Vanderbilt University, where she studied genes that regulate embryonic pancreas development and expression of the insulin gene. Dr. Gannon joined the Vanderbilt faculty in 2001. She is currently Professor and Vice Chair for Faculty Development in the Department of Medicine at Vanderbilt University with secondary appointments in the Departments of Molecular Physiology & Biophysics and Cell & Developmental Biology. The research in her laboratory focuses on the function and regeneration of insulin-producing beta cells. Her work has implications for Type 1 and Type 2 diabetes. Her research has been funded by grants from the NIH, JDRF, ADA, and the VA. Dr. Gannon has presented her research at conferences in the US, Europe, Asia, and the Middle East. She lives in Nashville, TN with her husband and son. In her spare time she performs in Celtic singing and Irish Step Dancing, having performed at the Ryman Auditorium with The Chieftains, onstage at the Grand Old Opry, and at TPAC. She also sings in her church music group and volunteers with her son’s boy scout troop.
The pancreas is essential for normal digestion and maintenance of blood sugar levels. We study the role of genes and signaling pathways involved in the development and function of specific cell types within the pancreas.
The Oc1/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. We developed mice in which Oc1 is over-expressed or can be inactivated conditionally. These studies reveal that Oc1 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 Oc1 interacts with other factors in the embryonic pancreas to regulate endocrine differentiation. Our studies also revealed that Oc1 is essential for normal growth and branching of the pancreatic ductal epithelium. In the absence of Oc1, pancreatic duct and acinar differentiation is impaired and the mice develop pancreatitis. We have discovered that Oc1 loss is associated with pancreatic cancer progression in humans.
A second project in the 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. We found that loss of CTGF results in decreased embryonic islet beta cell proliferation and defective islet formation. We are using conditional gene inactivation and over-expression strategies to determine how CTGF affects islet development and function during embryogenesis and after transplantation. In addition, we we have shown that CTGF can enhance beta cell regeneration in adults after significant beta cell destruction. The positive effects of CTGF on beta cell regeneration in this model require the cooperation of macrophages recruited to the islets following partial beta cell destruction. The factors produced by macrophages that sensitize beta cells to respond to CTGF are being identified.
Finally, the FoxM1 transcription factor is highly expressed in proliferating cells and is essential for normal cell division. We 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, we found that FoxM1 is required downstream of all proliferative stimuli in the insulin-producing beta cells. For example, the number of maternal beta cells expands via mitosis during pregnancy. In FoxM1 mutants, this increase in mitosis does not occur and the animals develop gestational diabetes. We have also shown that FoxM1 induction can rejuvenate older beta cells to become more proliferative, expanding beta cell mass in aged mice. 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. Two of the downstream effectors of FoxM1 are G-protein coupled receptors that bind the lipid signaling molecule prostaglandin E2 (PGE2). PGE2 is elevated in inflammatory states such as Type 2 diabetes. We are targeting the PGE2 receptors as a potential treatment for Type 2 diabetes.