Jorge Ferrer

Summary

URL: www.betacellregulation.net

Publications

  1. ncbi request reprint Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth
    Miguel Angel Maestro
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, Endocrinology, Hospital Clinic de Barcelona, Barcelona, Spain
    Endocr Dev 12:33-45. 2007
  2. doi request reprint GATA6 haploinsufficiency causes pancreatic agenesis in humans
    Hana Lango Allen
    Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
    Nat Genet 44:20-2. 2012
  3. pmc Functional targets of the monogenic diabetes transcription factors HNF-1alpha and HNF-4alpha are highly conserved between mice and humans
    Sylvia F Boj
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
    Diabetes 58:1245-53. 2009
  4. pmc Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets
    Reini F Luco
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions August Pi i Sunyer, Barcelona, Spain
    PLoS Genet 4:e1000079. 2008
  5. pmc Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene
    Ewan R Pearson
    Peninsula Medical School, Exeter, United Kingdom
    PLoS Med 4:e118. 2007
  6. pmc Putting pancreatic cell plasticity to the test
    Jorge Ferrer
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, Endocrinology Unit, Hospital Clinic de Barcelona, Barcelona, Spain
    J Clin Invest 117:859-62. 2007
  7. ncbi request reprint A conditional model reveals that induction of hepatocyte nuclear factor-1alpha in Hnf1alpha-null mutant beta-cells can activate silenced genes postnatally, whereas overexpression is deleterious
    Reini F Luco
    Endocrinology Unit, Hospital Clinic de Barcelona, Institut d Investigacions August Pi i Sunyer, Villarroel 170, Barcelona 08036, Spain
    Diabetes 55:2202-11. 2006
  8. ncbi request reprint A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes
    Jakob Ek
    Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
    Diabetes 55:1869-73. 2006
  9. pmc IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas
    Georg Mellitzer
    INSERM U682, Development and Physiopathology of the Intestine and Pancreas, Universite Louis Pasteur, Strasbourg, France
    EMBO J 25:1344-52. 2006
  10. ncbi request reprint The transcription factor hepatocyte nuclear factor-6 controls the development of pancreatic ducts in the mouse
    Christophe E Pierreux
    Hormone and Metabolic Research Unit, Université catholique de Louvain and Institute of Cellular Pathology, Brussels, Belgium
    Gastroenterology 130:532-41. 2006

Collaborators

Detail Information

Publications48

  1. ncbi request reprint Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth
    Miguel Angel Maestro
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, Endocrinology, Hospital Clinic de Barcelona, Barcelona, Spain
    Endocr Dev 12:33-45. 2007
    ..Collectively, these findings implicate HNF1beta as a regulator of pancreas organogenesis and differentiation, whereas HNF1alpha and HNF4alpha primarily regulate both growth and function of islet beta-cells...
  2. doi request reprint GATA6 haploinsufficiency causes pancreatic agenesis in humans
    Hana Lango Allen
    Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
    Nat Genet 44:20-2. 2012
    ..These findings define the most common cause of human pancreatic agenesis and establish a key role for the transcription factor GATA6 in human pancreatic development...
  3. pmc Functional targets of the monogenic diabetes transcription factors HNF-1alpha and HNF-4alpha are highly conserved between mice and humans
    Sylvia F Boj
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
    Diabetes 58:1245-53. 2009
    ..However, the significance of studies that assess binding without considering regulatory function is poorly understood...
  4. pmc Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets
    Reini F Luco
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions August Pi i Sunyer, Barcelona, Spain
    PLoS Genet 4:e1000079. 2008
    ..We have also revealed a defect in subnuclear gene positioning in a model of a human transcription factor disease...
  5. pmc Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene
    Ewan R Pearson
    Peninsula Medical School, Exeter, United Kingdom
    PLoS Med 4:e118. 2007
    ....
  6. pmc Putting pancreatic cell plasticity to the test
    Jorge Ferrer
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, Endocrinology Unit, Hospital Clinic de Barcelona, Barcelona, Spain
    J Clin Invest 117:859-62. 2007
    ..This finding points to an unexpected plasticity of postnatal pancreatic endocrine cells...
  7. ncbi request reprint A conditional model reveals that induction of hepatocyte nuclear factor-1alpha in Hnf1alpha-null mutant beta-cells can activate silenced genes postnatally, whereas overexpression is deleterious
    Reini F Luco
    Endocrinology Unit, Hospital Clinic de Barcelona, Institut d Investigacions August Pi i Sunyer, Villarroel 170, Barcelona 08036, Spain
    Diabetes 55:2202-11. 2006
    ..This finding illustrates the paramount importance of using the correct concentration of a beta-cell transcription factor in both gene therapy and artificial differentiation strategies...
  8. ncbi request reprint A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes
    Jakob Ek
    Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
    Diabetes 55:1869-73. 2006
    ..In conclusion, a rare, novel mutation that disrupts a protein binding site in the pancreatic HNF4A promoter associates with late-onset diabetes...
  9. pmc IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas
    Georg Mellitzer
    INSERM U682, Development and Physiopathology of the Intestine and Pancreas, Universite Louis Pasteur, Strasbourg, France
    EMBO J 25:1344-52. 2006
    ..IA1 is therefore a novel Ngn3-regulated factor required for normal differentiation of pancreatic endocrine cells...
  10. ncbi request reprint The transcription factor hepatocyte nuclear factor-6 controls the development of pancreatic ducts in the mouse
    Christophe E Pierreux
    Hormone and Metabolic Research Unit, Université catholique de Louvain and Institute of Cellular Pathology, Brussels, Belgium
    Gastroenterology 130:532-41. 2006
    ..Here, we investigate the transcriptional mechanisms that control pancreatic duct development by addressing the role of the transcription factor hepatocyte nuclear factor (HNF)-6...
  11. ncbi request reprint Transcriptional networks controlling pancreatic development and beta cell function
    J M Servitja
    Endocrinology, Hospital Clinic de Barcelona, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
    Diabetologia 47:597-613. 2004
    ..Finally, we propose that pancreatic gene programs might be manipulated to generate beta cells or to enhance the function of existing beta cells, thereby providing a possible treatment of different forms of diabetes...
  12. pmc Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver
    Joan Marc Servitja
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, Barcelona, Spain
    Mol Cell Biol 29:2945-59. 2009
    ..Collectively, these findings show that Hnf1alpha governs broad, highly tissue-specific genetic programs in pancreatic islets and liver and reveal key consequences of Hnf1a deficiency relevant to the pathophysiology of monogenic diabetes...
  13. doi request reprint PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression
    Benoit R Gauthier
    Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
    Cell Metab 10:110-8. 2009
    ..Thus, the genetic control by the beta cell-specific factor Pdx1 of the ubiquitous gene TFAM maintains beta cell mtDNA vital for ATP production and normal GSIS...
  14. doi request reprint Gene expression dynamics after murine pancreatitis unveils novel roles for Hnf1α in acinar cell homeostasis
    Xavier Molero
    Grup de Recerca en Patologia Pancreàtica Exocrina, Institut de Recerca Hospital Universitari Vall d Hebron, Pg Vall d Hebron 119 129, Barcelona 08035, Spain
    Gut 61:1187-96. 2012
    ..The objective of this study was to analyse the dynamic regulation of pancreatic genes and the role of transcriptional regulators during recovery from pancreatitis...
  15. doi request reprint Mapping open chromatin with formaldehyde-assisted isolation of regulatory elements
    Takao Nammo
    Genomic Programming of Beta Cells, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
    Methods Mol Biol 791:287-96. 2011
    ..Here we describe the implementation of the FAIRE method in human pancreatic islet cells...
  16. pmc Hepatic nuclear factor 1alpha (HNF1alpha) dysfunction down-regulates X-box-binding protein 1 (XBP1) and sensitizes beta-cells to endoplasmic reticulum stress
    Clare L Kirkpatrick
    Department of Cell Physiology and Metabolism, Centre Medical Universitaire, Universite de Geneve, 1 rue Michel Servet, 1211 Geneve 4, Switzerland
    J Biol Chem 286:32300-12. 2011
    ..Rat insulin 2 promoter-DN HNF1α mouse islets express lower levels of BiP mRNA, synthesize less insulin, and are sensitized to ER stress relative to matched control mouse islets, suggesting that this mechanism is also operating in vivo...
  17. ncbi request reprint Glucose as a mitogenic hormone
    Jorge Ferrer
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomèdiques August Pi iSunyer, Barcelona, Spain
    Cell Metab 13:357-8. 2011
    ..2011) combine genetic, transplantation, and pharmacologic approaches to show that glucose also stimulates β cell proliferation through similar metabolic signals, providing a new framework to develop therapeutics for diabetes...
  18. pmc EuroDia: a beta-cell gene expression resource
    Robin Liechti
    Vital IT, SIB Swiss Institute of Bioinformatics, Genopode Building, CH 1015 Lausanne, Switzerland
    Database (Oxford) 2010:baq024. 2010
    ..The flexible engine of this database (GEDAI) is currently used to handle gene expression data from several laboratory-run projects dealing with different organisms and platforms. Database URL: http://eurodia.vital-it.ch...
  19. pmc Epistasis of transcriptomes reveals synergism between transcriptional activators Hnf1alpha and Hnf4alpha
    Sylvia F Boj
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
    PLoS Genet 6:e1000970. 2010
    ..These findings provide an in vivo strategy to study combinatorial gene regulation and reveal how Hnf1alpha and Hnf4alpha control a common islet-cell regulatory program that is defective in human monogenic diabetes...
  20. pmc Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene activity program
    Joris van Arensbergen
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona 08036, Spain
    Genome Res 20:722-32. 2010
    ..These findings reveal a dynamic regulation of Polycomb repression programs that shape the identity of differentiated beta-cells...
  21. pmc Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis
    Intza Garin
    Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, 48903 Spain
    Proc Natl Acad Sci U S A 107:3105-10. 2010
    ..Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man...
  22. pmc A map of open chromatin in human pancreatic islets
    Kyle J Gaulton
    Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Nat Genet 42:255-9. 2010
    ..These findings illuminate the tissue-specific organization of cis-regulatory elements and show that FAIRE-seq can guide the identification of regulatory variants underlying disease susceptibility...
  23. doi request reprint Pancreatic exocrine duct cells give rise to insulin-producing beta cells during embryogenesis but not after birth
    Myriam Solar
    Genomic Programming of Beta Cells Laboratory, Institut d Investigacions Biomediques August Pi i Sunyer, 08036 Barcelona, Spain
    Dev Cell 17:849-60. 2009
    ..Thus, once the ductal epithelium differentiates it has a restricted plasticity, even under regenerative settings...
  24. ncbi request reprint Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas
    Miguel A Maestro
    Endocrinology, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
    Hum Mol Genet 12:3307-14. 2003
    ..These findings define a precursor cellular stage of the embryonic pancreas and place Hnf1beta in a genetic hierarchy that regulates the generation of pancreatic endocrine cells...
  25. ncbi request reprint Chromatin immunoprecipitation using isolated islets of Langerhans
    Marcelina Parrizas
    Hospital Clinic Universityari, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
    Methods Mol Med 83:61-71. 2003
  26. ncbi request reprint Mapping novel pancreatic islet genes to human chromosomes
    J Ferrer
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Diabetes 46:386-92. 1997
    ..These mapped ESTs may be used to assist in the positional cloning of diabetes susceptibility genes...
  27. ncbi request reprint Cloning of human pancreatic islet large conductance Ca(2+)-activated K+ channel (hSlo) cDNAs: evidence for high levels of expression in pancreatic islets and identification of a flanking genetic marker
    J Ferrer
    Division of Endocrinology, Diabetes, and Metabolism, Washington University School of Medicine, St Louis, MO 63110, USA
    Diabetologia 39:891-8. 1996
    ....
  28. ncbi request reprint Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians
    H Inoue
    Division of Metabolism, Diabetes and Endocrinology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Diabetes 45:825-31. 1996
    ..9% of patients and 0.5% of control subjects (P < 0.0001, OR 21.5, 95% CI 2.91-159.6). These results suggest that defects at the SUR locus may be a major contributor to the inherited basis of NIDDM in Northern European Caucasians...
  29. ncbi request reprint Mitochondrial glycerol-3-phosphate dehydrogenase. Cloning of an alternatively spliced human islet-cell cDNA, tissue distribution, physical mapping, and identification of a polymorphic genetic marker
    J Ferrer
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Diabetes 45:262-6. 1996
    ..These studies provide the means to investigate the role of the human mGPDH gene in the pathogenesis of NIDDM and illustrate the value of a novel strategy to identify genetic markers for diabetes candidate genes...
  30. ncbi request reprint Signals derived from glucose metabolism are required for glucose regulation of pancreatic islet GLUT2 mRNA and protein
    J Ferrer
    Endocrinology and Nutrition Unit, University of Barcelona School of Medicine, Spain
    Diabetes 42:1273-80. 1993
    ..In addition, ongoing RNA and protein synthesis are required for this effect...
  31. ncbi request reprint Expression of GLUT-2 antisense RNA in beta cells of transgenic mice leads to diabetes
    A Valera
    Department of Biochemistry and Molecular Biology, School of Veterinary Medicine, Autonomous University of Barcelona, Spain
    J Biol Chem 269:28543-6. 1994
    ..These results suggest that the reduction of GLUT-2 in the pancreas could be a crucial step in the development of diabetes mellitus...
  32. ncbi request reprint Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM
    A C Riggs
    Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA
    Diabetes 44:689-94. 1995
    ..Exons 2 and 3 each encode a LIM domain, while the homeodomain is completely contained within exon 4.(ABSTRACT TRUNCATED AT 250 WORDS)..
  33. ncbi request reprint Pancreatic islet cells express a family of inwardly rectifying K+ channel subunits which interact to form G-protein-activated channels
    J Ferrer
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 270:26086-91. 1995
    ..These results show that two components of islet cell KIR channels, CIR and GIRK2, may interact to form heteromeric G-protein-activated inwardly rectifying K+ channels that do not possess the typical properties of KATP channels...
  34. ncbi request reprint Pancreatic islet GLUT2 glucose transporter mRNA and protein expression in humans with and without NIDDM
    J Ferrer
    Endocrinology and Nutrition Service, University of Barcelona School of Medicine, Hospital Clinic, Spain
    Diabetes 44:1369-74. 1995
    ..Furthermore, the analysis of islet GLUT2 in a small sample of human organ donors with and without diabetes raises the possibility that decreased beta-cell GLUT2 may not represent a widespread feature of humans with NIDDM...
  35. ncbi request reprint A new 5-HT2 antagonist (ritanserin) in the treatment of chronic headache with depression. A double-blind study vs amitriptyline
    G Nappi
    Dept. of Neurology IRCCS C. Mondino, University of Pavia, Italy
    Headache 30:439-44. 1990
    ..Our data confirm the usefulness of these methods as markers of chronic headache with depression...
  36. ncbi request reprint Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM
    H Inoue
    Division of Endocrinology, Diabetes and Metabolism, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Diabetes 46:502-7. 1997
    ..Diabetes 45:825-831, 1996) and 2) did not contribute to the impaired insulin secretion characteristic of NIDDM in Caucasian patients...
  37. ncbi request reprint Early-onset type-II diabetes mellitus (MODY4) linked to IPF1
    D A Stoffers
    Nat Genet 17:138-9. 1997
  38. pmc Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function
    Sara K Hansen
    Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
    J Clin Invest 110:827-33. 2002
    ..Furthermore, they indicate that this regulation is essential to maintain normal pancreatic function...
  39. ncbi request reprint A genetic switch in pancreatic beta-cells: implications for differentiation and haploinsufficiency
    Jorge Ferrer
    Department of Endocrinology, Hospital Clinic i Universitari, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
    Diabetes 51:2355-62. 2002
    ..Such a model can serve to rationalize key aspects of the pathogenic mechanism in MODY...
  40. pmc A transcription factor regulatory circuit in differentiated pancreatic cells
    S F Boj
    Endocrinology and Hormonal Biochemistry Units, Hospital Clinic Universitari, Institut d Investigacions Biomediques August Pi i Sunyer, Villarroel 170, 08036 Barcelona, Spain
    Proc Natl Acad Sci U S A 98:14481-6. 2001
    ..Furthermore, they indicate that hnf1alpha is an essential component of a transcription factor circuit whose role may be to maintain differentiated functions of pancreatic cells...
  41. ncbi request reprint Genetic variability of the SUR1 promoter in relation to beta-cell function and Type II diabetes mellitus
    T Hansen
    Steno Diabetes Center, Gentofte, Denmark
    Diabetologia 44:1330-4. 2001
    ..We aimed to examine the promoter of SUR1 for genetic variation and to determine if variants were associated with Type II (non-insulin-dependent) diabetes mellitus or measures of beta-cell function...
  42. pmc Hepatic nuclear factor 1-alpha directs nucleosomal hyperacetylation to its tissue-specific transcriptional targets
    M Parrizas
    Endocrinology and Hormonal Biochemistry Units, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain 08036
    Mol Cell Biol 21:3234-43. 2001
    ..These findings provide genetic evidence based on a live mammalian system to establish that a single activator can be essential to direct nucleosomal hyperacetylation to transcriptional targets...
  43. ncbi request reprint Regulated expression of adenosine triphosphate-sensitive potassium channel subunits in pancreatic beta-cells
    W Moritz
    Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02114, USA
    Endocrinology 142:129-38. 2001
    ..2 minigene by about 2-fold. We propose that glucose- and GLP-1-dependent regulation of K(ATP) subunit genes may be important in the adaptation of beta-cells to changes in secretory demands in physiological and diseased states...
  44. pmc Molecular cloning and expression of novel sulphotransferase-like cDNAs from human and rat brain
    C N Falany
    Department of Pharmacology, 101 Volker Hall, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Biochem J 346:857-64. 2000
    ..The high degree of sequence conservation, and the selective localization of the BR-STL message in brain, suggest an important function in the central nervous system...
  45. ncbi request reprint CHOP/GADD153 and methionyl-tRNA synthetase (MetRS) genes overlap in a conserved region that controls mRNA stability
    M Ubeda
    Massachusetts General Hospital, Howard Hughes Medical Institute, Boston, Massachusetts 02114, USA
    Biochem Biophys Res Commun 262:31-8. 1999
    ..The conservation of this overlapping of the CHOP and MetRS genes and the role of their complementary sequence in the control of mRNA stability suggest the existence of a functional link between the expression of these two genes...
  46. ncbi request reprint Characterization of the mouse sulfonylurea receptor 1 promoter and its regulation
    C Hernandez-Sanchez
    Section on Molecular and Cellular Physiology, Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 1770, USA
    J Biol Chem 274:18261-70. 1999
    ..2 genes since glucocorticoids failed to affect the stability of each mRNA. Likewise, the reduction in mRNA levels was correlated with a decrease in SUR1 and Kir6.2 protein levels...
  47. ncbi request reprint Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene
    T Hansen
    Steno Diabetes Center and Hagedorn Research Institute, Glostrup University Hospital, Copenhagen, Denmark
    Diabetes 47:598-605. 1998
    ..In combination with an intron variant, the association is higher, and young, healthy carriers of the intragenic combination have reduced serum C-peptide and insulin responses to a tolbutamide load...