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Ole Madsen, Ph.D.

Principal Investigator
Hagedorn Research Institute
Beta Cell Biology

Niels Steensens Vej 6
Gentofte, DK-2820
Denmark

p. +45 4443 9197
f. +45 4443 8000
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Ole Madsen, Ph.D. - Investigator Profile

I have a longstanding interest in processes controlling beta-cell maturation. We have for several years studied pluripotent islet tumor cells - from which destinct hormone producing islet tumors could be derived from common clonal origin. More recently, we have studied processes of pancreas and islet beta-cell ontogeny. We are much interested in the signal transduction processes controlling pancreatic endocrine maturation. Much of our current focus relates to the translational aspect of developmental biology to coax pluripotent stem cell differentiation towards therapeutic beta cells for diabetes treatment. 

Our main focus with the BCBC is to generate novel antibody tools for important factors/markers for the different stages of pancreatic maturation. Such reagents will be made available through the Antibody Core.

Scientific Interests/Keywords

antibody, cell surface, epitope, extracellular, cell lineage tracing, fluorescent cells, antibody tags, cell sorting, cell separation, cell culture, antibody mediated cell purification, protocol development.

Affiliates

Click to view the profile for Inger Lund Pedersen.
Click to view the profile for Toby Brunt.
Click to view the profile for Stina Mikkelsen.
Click to view the profile for Jacob Hald, Ph.D..
Click to view the profile for Jonas Ahnfelt-Ronne.
Click to view the profile for Nicolaj Rasmussen, Ph.D.

Publications

PubMedID Citation
20558340 Galbo T, Pedersen IL, Fløyel T, Bang-Berthelsen CH, Serup P, Madsen OD, Hald J. Novel monoclonal antibodies against Pdx1 reveal feedback regulation of Pdx1 protein levels. (2010) Eur J Histochem 54: e19
20336589 Hansson M, Madsen OD. Pluripotent stem cells, a potential source of beta-cells for diabetes therapy. (2010) Curr Opin Investig Drugs 11: 417-25
19665969 Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S, Billestrup N, Madsen OD, Serup P, Heimberg H, Mansouri A. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. (2009) Cell 138: 449-62
19213833 Holst B, Egerod KL, Jin C, Petersen PS, Østergaard MV, Hald J, Sprinkel AM, Størling J, Mandrup-Poulsen T, Holst JJ, Thams P, Orskov C, Wierup N, Sundler F, Madsen OD, Schwartz TW. G protein-coupled receptor 39 deficiency is associated with pancreatic islet dysfunction. (2009) Endocrinology 150: 2577-85
18845151 Gustavsen CR, Chevret P, Krasnov B, Mowlavi G, Madsen OD, Heller RS. The morphology of islets of Langerhans is only mildly affected by the lack of Pdx-1 in the pancreas of adult Meriones jirds. (2008) Gen Comp Endocrinol 159: 241-9
18665014 Klein T, Heremans Y, Heimberg H, Pipeleers D, Madsen OD, Serup P, Heller RS. Investigation and characterization of the duct cell-enriching process during serum-free suspension and monolayer culture using the human exocrine pancreas fraction. () Pancreas 38: 36-48
18347078 Hald J, Sprinkel AE, Ray M, Serup P, Wright C, Madsen OD. Generation and characterization of Ptf1a antiserum and localization of Ptf1a in relation to Nkx6.1 and Pdx1 during the earliest stages of mouse pancreas development. (2008) J Histochem Cytochem 56: 587-95
18212389 Klinck R, Serup P, Madsen OD, Jørgensen MC. Specificity of four monoclonal anti-NKx6-1 antibodies. (2008) J Histochem Cytochem 56: 415-24
17881611 Jørgensen MC, Ahnfelt-Rønne J, Hald J, Madsen OD, Serup P, Hecksher-Sørensen J. An illustrated review of early pancreas development in the mouse. (2007) Endocr Rev 28: 685-705
17631449 Madsen OD. Pancreas phylogeny and ontogeny in relation to a 'pancreatic stem cell'. (2007) C R Biol 330: 534-7
17478445 Ahnfelt-Rønne J, Jørgensen MC, Hald J, Madsen OD, Serup P, Hecksher-Sørensen J. An improved method for three-dimensional reconstruction of protein expression patterns in intact mouse and chicken embryos and organs. (2007) J Histochem Cytochem 55: 925-30
17160042 Madsen OD, Serup P. Towards cell therapy for diabetes. (2006) Nat Biotechnol 24: 1481-3
17053071 Narendran P, Neale AM, Lee BH, Ngui K, Steptoe RJ, Morahan G, Madsen O, Dromey JA, Jensen KP, Harrison LC. Proinsulin is encoded by an RNA splice variant in human blood myeloid cells. (2006) Proc Natl Acad Sci U S A 103: 16430-5
16984985 Hainerova I, Torekov SS, Ek J, Finkova M, Borch-Johnsen K, Jorgensen T, Madsen OD, Lebl J, Hansen T, Pedersen O. Association between neuromedin U gene variants and overweight and obesity. (2006) J Clin Endocrinol Metab 91: 5057-63
16480455 Madsen OD. Stem cells and diabetes treatment. (2005) APMIS 113: 858-75
16401696 Pedersen IL, Klinck R, Hecksher-Sorensen J, Zahn S, Madsen OD, Serup P, Jorgensen MC. Generation and characterization of monoclonal antibodies against the transcription factor Nkx6.1. (2006) J Histochem Cytochem 54: 567-74
16122727 Heller RS, Jenny M, Collombat P, Mansouri A, Tomasetto C, Madsen OD, Mellitzer G, Gradwohl G, Serup P. Genetic determinants of pancreatic epsilon-cell development. (2005) Dev Biol 286: 217-24
15983231 Torekov SS, Larsen LH, Glumer C, Borch-Johnsen K, Jorgensen T, Holst JJ, Madsen OD, Hansen T, Pedersen O. Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes. (2005) Diabetes 54: 2261-5
15684667 Zahn S, Pedersen J, Serup IL, Madsen P. Generation of monoclonal antibodies against mouse neurogenin 3: a new immunocytochemical tool to study the pancreatic endocrine progenitor cell. (2004) Hybrid Hybridomics 23: 385-8
15543206 Rescan C, Lefebvre S, Frandsen VH, Klein U, Foschi T, Pipeleers M, Scharfmann DG, Madsen R, Heimberg OD. EGF-induced proliferation of adult human pancreatic duct cells is mediated by the MEK/ERK cascade. (2005) Lab Invest 85: 65-74
15031110 Heller RS, Stoffers DA, Liu A, Schedl A, Crenshaw EB, Madsen OD, Serup P. The role of Brn4/Pou3f4 and Pax6 in forming the pancreatic glucagon cell identity. (2004) Dev Biol 268: 123-34
14686787 Heller RS, Klein T, Ling Z, Heimberg H, Katoh M, Madsen OD, Serup P. Expression of Wnt, Frizzled, sFRP, and DKK genes in adult human pancreas. (2003) Gene Expr 11: 141-7
12921743 Hald J, Hjorth JP, German MS, Madsen OD, Serup P, Jensen J. Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. (2003) Dev Biol 260: 426-37
12754281 Klein T, Ling Z, Heimberg H, Madsen OD, Heller RS, Serup P. Nestin is expressed in vascular endothelial cells in the adult human pancreas. (2003) J Histochem Cytochem 51: 697-706
12412008 Heller RS, Dichmann DS, Jensen J, Miller C, Wong G, Madsen OD, Serup P. Expression patterns of Wnts, Frizzleds, sFRPs, and misexpression in transgenic mice suggesting a role for Wnts in pancreas and foregut pattern formation. (2002) Dev Dyn 225: 260-70
12403815 Heremans Y, Gradwohl M, Serup P, Madsen G, Pipeleers P, Heimberg O. Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3. (2002) J Cell Biol 159: 303-12
11423476 Heller RS, Stoffers DA, Bock T, Svenstrup K, Jensen J, Horn T, Miller CP, Habener JF, Madsen OD, Serup P. Improved glucose tolerance and acinar dysmorphogenesis by targeted (2001) Diabetes 50: 1553-61
11141151 Serup P, Madsen OD, Mandrup-Poulsen T. Islet and stem cell transplantation for treating diabetes. (2001) BMJ 322: 29-32
10969830 Ammendrup A, Maillard A, Nielsen K, Aabenhus Andersen N, Serup P, Dragsbaek Madsen O, Mandrup-Poulsen T, Bonny C. The c-Jun amino-terminal kinase pathway is preferentially activated by (2000) Diabetes 49: 1468-76
10891400 Petersen HV, Jorgensen MC, Andersen FG, Jensen J, F-Nielsen T, Jorgensen R, Madsen OD, Serup P. Pax4 represses pancreatic glucagon gene expression. (2000) Mol Cell Biol Res Commun 3: 249-54
10868931 Jensen J, Heller RS, Funder-Nielsen T, Pedersen EE, Lindsell C, Weinmaster G, Madsen OD, Serup P. Independent development of pancreatic alphaand beta-cells from (2000) Diabetes 49: 163-76
10825208 Jacquemin P, Durviaux SM, Jensen J, Godfraind C, Gradwohl G, Guillemot F, Madsen OD, Carmeliet P, Dewerchin M, Collen D, Rousseau GG, Lemaigre FP. Transcription factor hepatocyte nuclear factor 6 regulates pancreatic (2000) Mol Cell Biol 20: 4445-54
10628902 Tyrberg B, Eizirik DL, Marklund SL, Olejnicka B, Madsen OD, Andersson A. Human islets in mixed islet grafts protect mouse pancreatic beta-cells from alloxan toxicity. (1999) Pharmacol Toxicol 85: 269-75
10615124 Jensen J, Pedersen EE, Galante P, Hald J, Heller RS, Ishibashi M, Kageyama R, Guillemot F, Serup P, Madsen OD. Control of endodermal endocrine development by Hes-1. (2000) Nat Genet 24: 36-44
10580420 Nielsen K, Karlsen AE, Deckert M, Madsen OD, Serup P, Mandrup-Poulsen T, Nerup J. Beta-cell maturation leads to in vitro sensitivity to cytotoxins. (1999) Diabetes 48: 2324-32
10567713 Jørgensen MC, Vestergård Petersen H, Ericson J, Madsen OD, Serup P. Cloning and DNA-binding properties of the rat pancreatic beta-cell-specific factor Nkx6.1. (1999) FEBS Lett 461: 287-94
10424881 Tingstedt JE, Edlund H, Madsen OD, Larsson LI. Gastric amylin expression. Cellular identity and lack of requirement for the homeobox protein PDX-1. A study in normal and PDX-1-deficient animals with a cautionary note on antiserum evaluation. (1999) J Histochem Cytochem 47: 973-80
10375461 Luna G, Francini F, Gómez Dumm CL, Madsen O, Gagliardino JJ. Hormone coexpression in the adult toad endocrine pancreas: double-label immunofluorescence under basal conditions and after glucose injection. (1999) Gen Comp Endocrinol 115: 29-36
10214934 Jensen PB, Kristensen P, Clausen JT, Judge ME, Hastrup S, Thim L, Wulff BS, Foged C, Jensen J, Holst JJ, Madsen OD. The hypothalamic satiety peptide CART is expressed in anorectic and non-anorectic pancreatic islet tumors and in the normal islet of Langerhans. (1999) FEBS Lett 447: 139-43
10094480 Andersen FG, Jensen J, Heller RS, Petersen HV, Larsson LI, Madsen OD, Serup P. Pax6 and Pdx1 form a functional complex on the rat somatostatin gene upstream enhancer. (1999) FEBS Lett 445: 315-20
10094478 Andersen FG, Heller RS, Petersen HV, Jensen J, Madsen OD, Serup P. Pax6 and Cdx2/3 form a functional complex on the rat glucagon gene promoter G1-element. (1999) FEBS Lett 445: 306-10
9870681 Azzoni C, D'Adda T, Tamburrano G, Coscelli C, Madsen OD, Scopsi L, Bordi C. Functioning human insulinomas. An immunohistochemical analysis of intracellular insulin processing. (1998) Virchows Arch 433: 495-504
9714543 Petersen HV, Peshavaria M, Pedersen AA, Philippe J, Stein R, Madsen OD, Serup P. Glucose stimulates the activation domain potential of the PDX-1 homeodomain transcription factor. (1998) FEBS Lett 431: 362-6
9603781 Oster A, Jensen J, Serup P, Galante P, Madsen OD, Larsson LI. Rat endocrine pancreatic development in relation to two homeobox gene products (Pdx-1 and Nkx 6.1). (1998) J Histochem Cytochem 46: 707-15
9590691 Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup S. Hypothalamic CART is a new anorectic peptide regulated by leptin. (1998) Nature 393: 72-6
9435324 Jensen PB, Blume N, Mikkelsen JD, Larsen PJ, Jensen HI, Holst JJ, Madsen OD. Transplantable rat glucagonomas cause acute onset of severe anorexia and adipsia despite highly elevated NPY mRNA levels in the hypothalamic arcuate nucleus. (1998) J Clin Invest 101: 503-10
9230347 Madsen OD, Jensen J, Petersen HV, Pedersen EE, Oster A, Andersen FG, Jørgensen MC, Jensen PB, Larsson LI, Serup P. Transcription factors contributing to the pancreatic beta-cell phenotype. (1997) Horm Metab Res 29: 265-70
9025070 Larsson LI, Madsen OD, Serup P, Jonsson J, Edlund H. Pancreatic-duodenal homeobox 1 -role in gastric endocrine patterning. (1996) Mech Dev 60: 175-84
9022666 Madsen OD, Jensen J, Blume N, Petersen HV, Lund K, Karlsen C, Andersen FG, Jensen PB, Larsson LI, Serup P. Pancreatic development and maturation of the islet B cell. Studies of pluripotent islet cultures. (1996) Eur J Biochem 242: 435-45
8799146 Serup P, Jensen J, Andersen FG, Jørgensen MC, Blume N, Holst JJ, Madsen OD. Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1. (1996) Proc Natl Acad Sci U S A 93: 9015-20
8702531 Jensen J, Serup P, Karlsen C, Nielsen TF, Madsen OD. mRNA profiling of rat islet tumors reveals nkx 6.1 as a beta-cell-specific homeodomain transcription factor. (1996) J Biol Chem 271: 18749-58
8692940 Heimberg H, De Vos A, Moens K, Quartier E, Bouwens L, Pipeleers D, Van Schaftingen E, Madsen O, Schuit F. The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells. (1996) Proc Natl Acad Sci U S A 93: 7036-41
8501199 Jensen CH, Teisner B, Højrup P, Rasmussen HB, Madsen OD, Nielsen B, Skjødt K. Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2. (1993) Hum Reprod 8: 635-41
8421685 Deltour L, Leduque P, Blume N, Madsen O, Dubois P, Jami J, Bucchini D. Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo. (1993) Proc Natl Acad Sci U S A 90: 527-31
8404649 Madsen OD, Karlsen C, Nielsen E, Lund K, Kofod H, Welinder B, Rehfeld JF, Larsson LI, Steiner DF, Holst JJ. The dissociation of tumor-induced weight loss from hypoglycemia in a transplantable pluripotent rat islet tumor results in the segregation of stable alpha- and beta-cell tumor phenotypes. (1993) Endocrinology 133: 2022-30
8148038 Lund K, Blume N, Michelsen BK, Bucchini D, Madsen OD. Differential expression of non-allelic insulin genes in rodent islet tumour cells. (1993) J Mol Endocrinol 11: 305-18
7937976 Petersen HV, Serup P, Leonard J, Michelsen BK, Madsen OD. Transcriptional regulation of the human insulin gene is dependent on the homeodomain protein STF1/IPF1 acting through the CT boxes. (1994) Proc Natl Acad Sci U S A 91: 10465-9
7652479 Madsen OD, Karlsen C, Blume N, Jensen HI, Larsson LI, Holst JJ. Transplantable glucagonomas derived from pluripotent rat islet tumor tissue cause severe anorexia and adipsia. (1995) Scand J Clin Lab Invest Suppl 220: 27-35
7593609 Blume N, Skouv J, Larsson LI, Holst JJ, Madsen OD. Potent inhibitory effects of transplantable rat glucagonomas and insulinomas on the respective endogenous islet cells are associated with pancreatic apoptosis. (1995) J Clin Invest 96: 2227-35
7575438 Serup P, Petersen HV, Pedersen EE, Edlund H, Leonard J, Petersen JS, Larsson LI, Madsen OD. The homeodomain protein IPF-1/STF-1 is expressed in a subset of islet cells and promotes rat insulin 1 gene expression dependent on an intact E1 helix-loop-helix factor binding site. (1995) Biochem J 310 ( Pt 3): 997-1003
7540573 Karlsen AE, Andersen HU, Vissing H, Larsen PM, Fey SJ, Cuartero BG, Madsen OD, Petersen JS, Mortensen SB, Mandrup-Poulsen T. Cloning and expression of cytokine-inducible nitric oxide synthase cDNA from rat islets of Langerhans. (1995) Diabetes 44: 753-8
6207064 Madsen OD, Frank BH, Steiner DF. Human proinsulin-specific antigenic determinants identified by monoclonal antibodies. (1984) Diabetes 33: 1012-6
6196183 Madsen OD, Cohen RM, Fitch FW, Rubenstein AH, Steiner DF. The production and characterization of monoclonal antibodies specific for human proinsulin using a sensitive microdot assay procedure. (1983) Endocrinology 113: 2135-44
3896518 Orci L, Ravazzola M, Amherdt M, Madsen O, Vassalli JD, Perrelet A. Direct identification of prohormone conversion site in insulin-secreting cells. (1985) Cell 42: 671-81
3537136 Contreas G, Madsen OD, Vissing H, Lernmark A. A simple assay for the detection of antibodies to endocrine islet cell surface antigens. (1986) J Immunol Methods 95: 135-9
3536964 Orci L, Ravazzola M, Amherdt M, Madsen O, Perrelet A, Vassalli JD, Anderson RG. Conversion of proinsulin to insulin occurs coordinately with acidification of maturing secretory vesicles. (1986) J Cell Biol 103: 2273-81
3516766 Madsen OD, Olsson ML, Bille G, Sundkvist G, Lernmark A, Dahlqvist G, Ludvigsson J. A two-colour immunofluorescence test with a monoclonal human proinsulin antibody improves the assay for islet cell antibodies. (1986) Diabetologia 29: 115-8
2877997 Madsen OD, Larsson LI, Rehfeld JF, Schwartz TW, Lernmark A, Labrecque AD, Steiner DF. Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones. (1986) J Cell Biol 103: 2025-34
2842785 Madsen OD, Andersen LC, Michelsen B, Owerbach D, Larsson LI, Lernmark A, Steiner DF. Tissue-specific expression of transfected human insulin genes in pluripotent clonal rat insulinoma lines induced during passage in vivo. (1988) Proc Natl Acad Sci U S A 85: 6652-6
2805585 Contreas G, Dyrberg T, Madsen OD, Markholst H, Lernmark A. Increased levels of circulating immune complexes are not associated with diabetes in BB rats. (1989) Diabetes Res 10: 109-13
2663499 Larsson LI, Nielsen JH, Hutton JC, Madsen OD. Pancreatic hormones are expressed on the surfaces of human and rat islet cells through exocytotic sites. (1989) Eur J Cell Biol 48: 45-51
2644530 Nielsen JH, Linde S, Welinder BS, Billestrup N, Madsen OD. Growth hormone is a growth factor for the differentiated pancreatic beta-cell. (1989) Mol Endocrinol 3: 165-73
2644126 Bucchini D, Madsen O, Desbois P, Pictet R, Jami J. B islet cells of pancreas are the site of expression of the human insulin gene in transgenic mice. (1989) Exp Cell Res 180: 467-74
2550269 Beck TC, Madsen OD. Monoclonal antibodies as probes to the differentiated exocrine pancreas react to monoclonal islet tumor tissue. (1989) Exp Clin Endocrinol 93: 255-60
2443408 Madsen OD. Proinsulin-specific monoclonal antibodies. Immunocytochemical application as beta-cell markers and as probes for conversion. (1987) Diabetes 36: 1203-11
2274051 Fromont-Racine M, Bucchini D, Madsen O, Desbois P, Linde S, Nielsen JH, Saulnier C, Ripoche MA, Jami J, Pictet R. Effect of 5'-flanking sequence deletions on expression of the human insulin gene in transgenic mice. (1990) Mol Endocrinol 4: 669-77
2199167 Madsen OD, Contreas G, Jørgensen J. Monoclonal (auto)antibodies in insulin-dependent diabetes mellitus. (1990) Curr Top Microbiol Immunol 156: 75-86
2169420 Nielsen E, Welinder B, Madsen OD. Protein HMG-17 is hyper-expressed in rat glucagonoma. Single-step isolation and sequencing. (1990) Eur J Biochem 192: 81-6
2122446 Contreas G, Jørgensen J, Madsen OD. Novel islet, duct, and acinar cell markers defined by monoclonal autoantibodies from prediabetic BB rats. (1990) Pancreas 5: 540-7
1989847 Fürnsinn C, Komjati M, Madsen OD, Schneider B, Waldhäusl W. Lifelong sequential changes in glucose tolerance and insulin secretion in genetically obese Zucker rats (fa/fa) fed a diabetogenic diet. (1991) Endocrinology 128: 1093-9
1954895 Nielsen E, Welinder BS, Madsen OD. Chromogranin-B, a putative precursor of eight novel rat glucagonoma peptides through processing at mono-, di-, or tribasic residues. (1991) Endocrinology 129: 3147-56
1924335 Michelsen BK, Petersen JS, Boel E, Møldrup A, Dyrberg T, Madsen OD. Cloning, characterization, and autoimmune recognition of rat islet glutamic acid decarboxylase in insulin-dependent diabetes mellitus. (1991) Proc Natl Acad Sci U S A 88: 8754-8
1850107 Madsen OD, Nielsen JH, Michelsen B, Westermark P, Betsholtz C, Nishi M, Steiner DF. Islet amyloid polypeptide and insulin expression are controlled differently in primary and transformed islet cells. (1991) Mol Endocrinol 5: 143-8
1734887 De Vroede M, Foriers A, Van de Winkel M, Madsen O, Pipeleers D. Presence of islet amyloid polypeptide in rat islet B and D cells determines parallelism and dissociation between rat pancreatic islet amyloid polypeptide and insulin content. (1992) Biochem Biophys Res Commun 182: 886-93
1569972 Blume N, Petersen JS, Andersen LC, Kofod H, Dyrberg T, Michelsen BK, Serup P, Madsen OD. Immature transformed rat islet beta-cells differentially express C-peptides derived from the genes coding for insulin I and II as well as a transfected human insulin gene. (1992) Mol Endocrinol 6: 299-307
1563584 In 't Veld PA, Zhang F, Madsen OD, Klöppel G. Islet amyloid polypeptide immunoreactivity in the human fetal pancreas. (1992) Diabetologia 35: 272-6
1406710 Møller CJ, Christgau S, Williamson MR, Madsen OD, Niu ZP, Bock E, Baekkeskov S. Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas. (1992) Mol Endocrinol 6: 1332-42

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