Vanderbilt University School of Medicine

Gannon, Maureen Anne , Ph.D.
Associate Professor of Medicine
Associate Professor of Molecular Physiology and Biophysics
Associate Professor of Cell and Developmental Biology

Lab Url:

Phone Number: 615-936-2676

Email Address:maureen.gannon@Vanderbilt.Edu

Gannon, Maureen's picture

Office Address   Mailing Address

7425C MRBIV Langford

Division of Diabetes, Endocrinology and Metabolism 7425 MRBIV Langford 37232-0475

Research Keywords
Molecular genetics of pancreas development, organogenesis, morphogenesis, islet function, diabetes, transcription factors, pancreatic cancer,Cancer,Cell cycle,Developmental biology,Diabetes,Gene regulation,Knockout,Mouse,Mutation,Stem cells,Transcription factor

Research Description
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 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 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. Our 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 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 are examining whether CTGF can enhance beta cell regeneration in adults after significant beta cell destruction.

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 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. Our 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.

Clinical Interests

Matsuoka, TA, Kaneto, H, Kawashima, S, Miyatsuka, T, Tochino, Y, Yoshikawa, A, Imagawa, A, Miyazaki, J, Gannon, M, Stein, R, Shimomura, I. Preserving Mafa Expression in Diabetic Islet ??-Cells Improves Glycemic Control in Vivo. J Biol Chem, 290(12), 7647-57, 2015.

Mosser, RE, Maulis, MF, Moull??, VS, Dunn, JC, Carboneau, BA, Arasi, K, Pappan, K, Poitout, V, Gannon, M. High-fat diet-induced ??-cell proliferation occurs prior to insulin resistance in C57Bl/6J male mice. Am J Physiol Endocrinol Metab, 308(7), E573-82, 2015.

Riley, KG, Pasek, RC, Maulis, MF, Peek, J, Thorel, F, Brigstock, DR, Herrera, PL, Gannon, M. Connective Tissue Growth Factor Modulates Adult ??-Cell Maturity and Proliferation to Promote ??-Cell Regeneration in Mice. Diabetes, 64(4), 1284-98, 2015.

Golson, ML, Maulis, MF, Dunn, JC, Poffenberger, G, Schug, J, Kaestner, KH, Gannon, MA. Activated FoxM1 attenuates streptozotocin-mediated ??-cell death. Mol Endocrinol, 28(9), 1435-47, 2014.

Pekala, KR, Ma, X, Kropp, PA, Petersen, CP, Hudgens, CW, Chung, CH, Shi, C, Merchant, NB, Maitra, A, Means, AL, Gannon, MA. Loss of HNF6 expression correlates with human pancreatic cancer progression. Lab Invest, 94(5), 517-27, 2014.

Alfaro, MP, Deskins, DL, Wallus, M, DasGupta, J, Davidson, JM, Nanney, LB, A Guney, M, Gannon, M, Young, PP. A physiological role for connective tissue growth factor in early wound healing. Lab Invest, 93(1), 81-95, 2013.

Mosser, RE, Gannon, M. An assay for small scale screening of candidate ?? cell proliferative factors using intact islets. Biotechniques, 55(6), 310-2, 2013.

Gunasekaran, U, Hudgens, CW, Wright, BT, Maulis, MF, Gannon, M. Differential regulation of embryonic and adult I? cell replication. Cell Cycle, 11(13), , 2012.

Henley, KD, Gooding, KA, Economides, AN, Gannon, M. Inactivation of the dual Bmp/Wnt inhibitor Sostdc1 enhances pancreatic islet function. Am J Physiol Endocrinol Metab, 303(6), E752-61, 2012.

Reinert, RB, Kantz, J, Misfeldt, AA, Poffenberger, G, Gannon, M, Brissova, M, Powers, AC. Tamoxifen-Induced Cre-loxP Recombination Is Prolonged in Pancreatic Islets of Adult Mice. PLoS One, 7(3), e33529, 2012. PMCID:3314663

Vanderpool, C, Sparks, EE, Huppert, KA, Gannon, M, Means, AL, Huppert, SS. Genetic interactions between hepatocyte nuclear factor-6 and Notch signaling regulate mouse intrahepatic bile duct development in vivo. Hepatology, 55(1), 233-43, 2012. PMCID:3314663

Gunasekaran, U, Gannon, M. Type 2 diabetes and the aging pancreatic beta cell. Aging (Albany NY), 3(6), 565-75, 2011. PMCID:3164365

Guney, MA, Petersen, CP, Boustani, A, Duncan, MR, Gunasekaran, U, Menon, R, Warfield, C, Grotendorst, GR, Means, AL, Economides, AN, Gannon, M. Connective tissue growth factor acts within both endothelial cells and beta cells to promote proliferation of developing beta cells. Proc Natl Acad Sci U S A, 108(37), 15242-7, 2011. PMCID:3174622

Moore, MC, Menon, R, Coate, KC, Gannon, M, Smith, MS, Farmer, B, Williams, PE. Diet-induced impaired glucose tolerance and gestational diabetes in the dog. J Appl Physiol, 110(2), 458-67, 2011. PMCID:3043793

Blaine, SA, Ray, KC, Anunobi, R, Gannon, MA, Washington, MK, Means, AL. Adult pancreatic acinar cells give rise to ducts but not endocrine cells in response to growth factor signaling. Development, 137(14), 2289-96, 2010.

Golson, ML, Misfeldt, AA, Kopsombut, UG, Petersen, CP, Gannon, M. High Fat Diet Regulation of ??-Cell Proliferation and ??-Cell Mass. Open Endocrinol J, 4, , 2010.

Crawford, LA, Guney, MA, Oh, YA, Deyoung, RA, Valenzuela, DM, Murphy, AJ, Yancopoulos, GD, Lyons, KM, Brigstock, DR, Economides, A, Gannon, M. Connective tissue growth factor (CTGF) inactivation leads to defects in islet cell lineage allocation and beta-cell proliferation during embryogenesis. Mol Endocrinol, 23(3), 324-36, 2009. PMCID:2654514

Elghazi, L, Weiss, AJ, Barker, DJ, Callaghan, J, Staloch, L, Sandgren, EP, Gannon, M, Adsay, VN, Bernal-Mizrachi, E. Regulation of pancreas plasticity and malignant transformation by Akt signaling. Gastroenterology, 136(3), 1091-103, 2009. PMCID:2739876

Guney, MA, Gannon, M. Pancreas cell fate. Birth Defects Res C Embryo Today, 87(3), 232-48, 2009. PMCID:2755625

Virostko, J, Radhika, A, Poffenberger, G, Chen, Z, Brissova, M, Gilchrist, J, Coleman, B, Gannon, M, Jansen, ED, Powers, AC. Bioluminescence Imaging in Mouse Models Quantifies beta Cell Mass in the Pancreas and After Islet Transplantation. Mol Imaging Biol, , , 2009.

Zhang, H, Ables, ET, Pope, CF, Washington, MK, Hipkens, S, Means, AL, Path, G, Seufert, J, Costa, RH, Leiter, AB, Magnuson, MA, Gannon, M. Multiple, temporal-specific roles for HNF6 in pancreatic endocrine and ductal differentiation. Mech Dev, 126(11-12), 958-73, 2009.

Zhang, H, Zhang, J, Pope, CF, Crawford, LA, Vasavada, RC, Jagasia, SM, Gannon, M. Gestational diabetes resulting from impaired {beta}-cell compensation in the absence of FoxM1, a novel downstream effector of placental lactogen. Diabetes, , , 2009.

Ackermann Misfeldt, A, Costa, RH, Gannon, M. Beta-cell proliferation, but not neogenesis, following 60% partial pancreatectomy is impaired in the absence of FoxM1. Diabetes, 57(11), 3069-77, 2008. PMCID:2570403

Gannon, M, Ables, ET, Crawford, L, Lowe, D, Offield, MF, Magnuson, MA, Wright, CV. pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. Dev Biol, 314(2), 406-17, 2008. PMCID:2269701

Wilding Crawford, L, Tweedie Ables, E, Oh, YA, Boone, B, Levy, S, Gannon, M. Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis. PLoS ONE, 3(2), e1611, 2008. PMCID:2249940

Ackermann, AM, Gannon, M. Molecular regulation of pancreatic {beta}-cell mass development, maintenance, and expansion. J Mol Endocrinol, 38(2), 193-206, 2007.

Gannon, M. BuMP-ing up Insulin Secretion by Pancreatic beta Cells. Cell Metab, 5(3), 157-9, 2007.

Kanetsuna, Y, Takahashi, K, Nagata, M, Gannon, MA, Breyer, MD, Harris, RC, Takahashi, T. Deficiency of endothelial nitric-oxide synthase confers susceptibility to diabetic nephropathy in nephropathy-resistant inbred mice. Am J Pathol, 170(5), 1473-84, 2007. PMCID:1854944

Wiebe, PO, Kormish, JD, Roper, VT, Fujitani, Y, Alston, NI, Zaret, KS, Wright, CV, Stein, RW, Gannon, M. Ptf1a binds to and activates area III, a highly conserved region of the Pdx1 promoter that mediates early pancreas-wide Pdx1 expression. Mol Cell Biol, 27(11), 4093-104, 2007. PMCID:1900007

Boyer, DF, Fujitani, Y, Gannon, M, Powers, AC, Stein, RW, Wright, CV. Complementation rescue of Pdx1 null phenotype demonstrates distinct roles of proximal and distal cis-regulatory sequences in pancreatic and duodenal expression. Dev Biol, 298(2), 616-31, 2006.

Brissova, M, Shostak, A, Shiota, M, Wiebe, PO, Poffenberger, G, Kantz, J, Chen, Z, Carr, C, Jerome, WG, Chen, J, Baldwin, HS, Nicholson, W, Bader, DM, Jetton, T, Gannon, M, Powers, AC. Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function. Diabetes, 55(11), 2974-85, 2006.

Fujitani, Y, Fujitani, S, Boyer, DF, Gannon, M, Kawaguchi, Y, Ray, M, Shiota, M, Stein, RW, Magnuson, MA, Wright, CV. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev, 20(2), 253-66, 2006. PMCID:1356115

Kanetsuna, Y, Hirano, K, Nagata, M, Gannon, MA, Takahashi, K, Harris, RC, Breyer, MD, Takahashi, T. Characterization of diabetic nephropathy in a transgenic model of hypoinsulinemic diabetes. Am J Physiol Renal Physiol, 291(6), F1315-22, 2006.

Tweedie, E, Artner, I, Crawford, L, Poffenberger, G, Thorens, B, Stein, R, Powers, AC, Gannon, M. Maintenance of hepatic nuclear factor 6 in postnatal islets impairs terminal differentiation and function of beta-cells. Diabetes, 55(12), 3264-70, 2006.

Zhang, H, Ackermann, AM, Gusarova, GA, Lowe, D, Feng, X, Kopsombut, UG, Costa, RH, Gannon, M. The Foxm1 Transcription Factor is Required to Maintain Pancreatic Beta Cell Mass. Mol Endocrinol, , , 2006.

Zhang, H, Fujitani, Y, Wright, CV, Gannon, M. Efficient recombination in pancreatic islets by a tamoxifen-inducible Cre-recombinase. Genesis, 42(3), 210-7, 2005.

Brissova, Marcela, Fowler, Michael, Wiebe, Peter, Shostak, Alena, Shiota, Masakazu, Radhika, Aramandla, Lin, P Charles, Gannon, Maureen, Powers, Alvin C. Intraislet endothelial cells contribute to revascularization of transplanted pancreatic islets. Diabetes, 53(5), 1318-25, 2004.

Frigeri, Claudia, Martin, Cyrus C, Svitek, Christina A, Oeser, James K, Hutton, John C, Gannon, Maureen, O''Brien, Richard M. The proximal islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen promoter is sufficient to initiate but not maintain transgene expression in mouse islets in vivo. Diabetes, 53(7), 1754-64, 2004.

Wilding, Laura, Gannon, Maureen. The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursors. Diabetes Metab Res Rev, 20(2), 114-23, 2004.

Brissova, Marcela, Shiota, Masakazu, Nicholson, Wendell E, Gannon, Maureen, Knobel, Susan M, Piston, David W, Wright, Christopher V E, Powers, Alvin C. Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. J Biol Chem, 277(13), 11225-32, 2002.

Kawaguchi, Yoshiya, Cooper, Bonnie, Gannon, Maureen, Ray, Michael, MacDonald, Raymond J, Wright, Christopher V E. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet, 32(1), 128-34, 2002.

Samaras, Susan E, Cissell, Michelle A, Gerrish, Kevin, Wright, Christopher V E, Gannon, Maureen, Stein, Roland. Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in Pancreatic beta cells: role for hepatocyte nuclear factor 3 beta and Pax6. Mol Cell Biol, 22(13), 4702-13, 2002. PMCID:133887

Zhang, Peichuan, McGrath, Barbara, Li, Sheng'ai, Frank, Ami, Zambito, Frank, Reinert, Jamie, Gannon, Maureen, Ma, Kun, McNaughton, Kelly, Cavener, Douglas R. The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Mol Cell Biol, 22(11), 3864-74, 2002. PMCID:133833

Dutta, S, Gannon, M, Peers, B, Wright, C, Bonner-Weir, S, Montminy, M. PDX:PBX complexes are required for normal proliferation of pancreatic cells during development. Proc Natl Acad Sci U S A, 98(3), 1065-70, 2001. PMCID:14709

Gannon, M. Molecular genetic analysis of diabetes in mice. Trends Genet, 17(10), S23-8, 2001.

Gannon, M, Gamer, L W, Wright, C V. Regulatory regions driving developmental and tissue-specific expression of the essential pancreatic gene pdx1. Dev Biol, 238(1), 185-201, 2001.

Gannon, M, Gilday, D, Rifkind, A B. TCDD induces CYP1A4 and CYP1A5 in chick liver and kidney and only CYP1A4, an enzyme lacking arachidonic acid epoxygenase activity, in myocardium and vascular endothelium. Toxicol Appl Pharmacol, 164(1), 24-37, 2000.

Gannon, M, Herrera, P L, Wright, C V. Mosaic Cre-mediated recombination in pancreas using the pdx-1 enhancer/promoter. Genesis, 26(2), 143-4, 2000.

Gannon, M, Ray, M K, Van Zee, K, Rausa, F, Costa, R H, Wright, C V. Persistent expression of HNF6 in islet endocrine cells causes disrupted islet architecture and loss of beta cell function. Development, 127(13), 2883-95, 2000.

Gannon, M, Shiota, C, Postic, C, Wright, C V, Magnuson, M. Analysis of the Cre-mediated recombination driven by rat insulin promoter in embryonic and adult mouse pancreas. Genesis, 26(2), 139-42, 2000.

Gerrish, K, Gannon, M, Shih, D, Henderson, E, Stoffel, M, Wright, C V, Stein, R. Pancreatic beta cell-specific transcription of the pdx-1 gene. The role of conserved upstream control regions and their hepatic nuclear factor 3beta sites. J Biol Chem, 275(5), 3485-92, 2000.

Song, S Y, Gannon, M, Washington, M K, Scoggins, C R, Meszoely, I M, Goldenring, J R, Marino, C R, Sandgren, E P, Coffey, R J, Wright, C V, Leach, S D. Expansion of Pdx1-expressing pancreatic epithelium and islet neogenesis in transgenic mice overexpressing transforming growth factor alpha. Gastroenterology, 117(6), 1416-26, 1999.

Gannon, M, Bader, D. Avian cardiac progenitors: methods for isolation, culture, and analysis of differentiation. Methods Cell Biol, 52, 117-32, 1997.

Wu, K L, Gannon, M, Peshavaria, M, Offield, M F, Henderson, E, Ray, M, Marks, A, Gamer, L W, Wright, C V, Stein, R. Hepatocyte nuclear factor 3beta is involved in pancreatic beta-cell-specific transcription of the pdx-1 gene. Mol Cell Biol, 17(10), 6002-13, 1997. PMCID:232449

Gilday, D, Gannon, M, Yutzey, K, Bader, D, Rifkind, A B. Molecular cloning and expression of two novel avian cytochrome P450 1A enzymes induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Chem, 271(51), 33054-9, 1996.

Gannon, M, Bader, D. Initiation of cardiac differentiation occurs in the absence of anterior endoderm. Development, 121(8), 2439-50, 1995.

Melnik, N, Yutzey, K E, Gannon, M, Bader, D. Commitment, differentiation, and diversification of avian cardiac progenitor cells. Ann N Y Acad Sci, 752, 1-8, 1995.

Yutzey, K, Gannon, M, Bader, D. Diversification of cardiomyogenic cell lineages in vitro. Dev Biol, 170(2), 531-41, 1995.

Nakai, K, Ward, A M, Gannon, M, Rifkind, A B. Beta-naphthoflavone induction of a cytochrome P-450 arachidonic acid epoxygenase in chick embryo liver distinct from the aryl hydrocarbon hydroxylase and from phenobarbital-induced arachidonate epoxygenase. J Biol Chem, 267(27), 19503-12, 1992.

Wang, G, Higgins, P J, Gannon, M, Staiano-Coico, L. Transforming growth factor-beta 1 acts cooperatively with sodium n-butyrate to induce differentiation of normal human keratinocytes. Exp Cell Res, 198(1), 27-30, 1992.

Rifkind, A B, Gannon, M, Gross, S S. Arachidonic acid metabolism by dioxin-induced cytochrome P-450: a new hypothesis on the role of P-450 in dioxin toxicity. Biochem Biophys Res Commun, 172(3), 1180-8, 1990.

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