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Hugo de Jonge

hugo de Jonge 0416-009Associate Professor
Room: Na-615
H.dejonge@erasmusmc.nl

Professional experience
Hugo de Jonge was born in Eindhoven, The Netherlands in 1944. He received his MSc (cum laude) in Biochemistry at the Free University in Amsterdam and his PhD at the Erasmus University in Rotterdam (1976) where he studied signal transduction by cyclic nucleotides and mitochondrial protein synthesis in intestinal epithelium. Following a postdoctoral training with Prof. Ohra Rosen at the Department of Pharmacology, Albert Einstein College of Medicine, New York and an EMBO Fellowship with Prof. Shmuel Shaltiel at the Department of Chemical Immunology, Weizmann Institute, Rehovot, Israel he became an associate and later full professor in Biochemistry at the Department of Biochemistry in Rotterdam, and served as a visiting professor at the Columbia University in New york (GI Reseach Department; head: Prof. Michael Field) and the University of Alberta in Edmonton (GI Department; head: Prof. Alan Thomson). From 2011 on, he continued his GI-related studies at the Department of Gastroenterology and Hepatology of the Erasmus Medical Center. During his research on mechanisms of ion transport regulation in epithelial cells and the molecular basis of chloride channelopathies such as secretory diarrhea (SD) and cystic fibrosis (CF), he discovered, cloned and characterized several key signaling enzymes (guanylyl cyclase-C, cyclic GMP-dependent protein kinase type II) involved in enterotoxin-induced diarrheal disease and identified their main molecular target, the CFTR choride channel.
Sofar he has published 198 full papers in high quality international journals. He has been a recipient of many prestigious awards including the Dutch Steven Hoogendijk Award (1999) and served as an Editor of the Biochemical Journal (1987-1995), Biochemica Biophysica Acta (2002-2007), and the J. Cystic Fibrosis (2000-present). He also served as the treasurer of the Board of the Dutch Biochemical Society (NVBMB: 1998-2007) and as a member of numerous scientific advisory boards, including the Cellular Physiology Study Section of the Neherlands Organization for the Advancement of Pure Research (NWO-ZON) (1983-1988; 1991; 1995-1996), the Dutch Foundation for Bio-Sciences (NWO-ALW) (1997-2001), the Flemish Science Organization (FWO section Medical Biochemistry) (2001-2009), and the Evaluation Panel Rare Diseases (7th Framework Programme, EU) (2007). He has been a (co-)organizer of many international conferences, including the Workshop "Disorders of Chloride Channel Regulation: Cystic Fibrosis and Secretory Diarrhoea", Royal Academy of Arts & Sciences, Amsterdam (1988), the FEBS Special Meeting on Cell Signaling Mechanisms, Amsterdam (1997), the 23th and 24th European Cystic Fibrosis Conference (The Hague, 1998; Vienna, 2001), and the 18th European Intestinal Transport Group Meeting, Egmond (2002).

Research focus
A major new research goal of his group is the in vivo rescue of mutant-CFTR function in cystic fibrosis mice by pharmacological approaches, and the ex vivo testing of promising candidate drugs by bioelectric assays in rectal biopsies and nasal mucosa, and fluid transport assays in intestinal organoids from cystic fibrosis patients. In addition, new approaches are explored to prevent excessive salt-and water loss in diarrheal diseases and diarrhea-predominant irritable bowel syndrome (IBS-D) by interfering with transmembrane signaling by microbial enterotoxins and endogenous secretagogues, in particular guanylin and uroguanylin. Conversely, pharmacological activators of the guanylin /guanylylcyclase /cyclicGMP signalling pathway are tested for their ability to restore luminal fluidity and intestinal motility in CF and in constipation-predominant IBS (IBS-C).

The researchgroup


Selected references:

  • Zachos NC, Kovbasnjuk O, Foulke-Abel J, In J, Blutt SE, De Jonge HR, Estes MK, Donowitz M.
    Human enteroids/colonoids and intestinal organoids functionally recapitulate normal intestinal physiology and pathophysiology.
    J Biol Chem. 2016 Feb 19;291(8):3759-66.

  • Foulke-Abel J, In J, Yin J, Zachos NC, Kovbasnjuk O, Estes MK, de Jonge H, Donowitz M.
    Human enteroids as a model of upper small intestinal ion transport physiology and pathophysiology.
    Gastroenterology. 2016 Mar;150(3):638-649.

  • Vidovic D, Carlon MS, F da Cunha M, Dekkers JF, Hollenhorst MI, Bijvelds MJ, Ramalho AS, Van den Haute C, Ferrante M, Baekelandt V, Janssens HM, De Boeck K, Sermet-Gaudelus I, de Jonge HR, Gijsbers R, Beekman JM, Edelman A, Debyser Z.
    rAAV-CFTR?R rescues the cystic fibrosis phenotype in human intestinal organoids and CF mice.
    Am J Respir Crit Care Med. 2016 Feb 1;193(3):288-98.

  • Bijvelds MJ, Loos M, Bronsveld I, Hellemans A, Bongartz JP, Ver Donck L, Cox E, de Jonge HR, Schuurkes JA, De Maeyer JH.
    Inhibition of heat-stable toxin-induced intestinal salt and water secretion by a novel class of guanylyl cyclase C inhibitors.
    J Infect Dis. 2015 Dec 1;212(11):1806-15.

  • Moon C, Zhang W, Ren A, Arora K, Sinha C, Yarlagadda S, Woodrooffe K, Schuetz JD, Valasani KR, de Jonge HR, Shanmukhappa SK, Shata MT, Buddington RK, Parthasarathi K, Naren AP.
    Compartmentalized accumulation of cAMP near complexes of multidrug resistance protein 4 (MRP4) and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) contributes to drug-induced diarrhea.
    J Biol Chem. 2015 May 1;290(18):11246-57

  • Chen T, Kocinsky HS, Cha B, Murtazina R, Yang J, Tse CM, Singh V, Cole R, Aronson PS, de Jonge H, Sarker R, Donowitz M.
    Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: Identification of a multifunctional phosphorylation site.
    J Biol Chem. 2015 Jan 23;290(4):1952-65.

  • Ikpa PT, Bijvelds MC, De Jonge HR.
    Cystic fibrosis: toward personalized therapies.
    Int J Biochem Cell Biol. 2014 Jul;52:192-200.

  • De Jonge HR, Tilly BC, Hogema BM, Pfau D, Kelly CA, Kelly M, Morris M, Melita AM, Viola R, Forrest Jr JN.
    cGMP Inhibition of type 3 phosphodiesterase is the major mechanism by which C-type natriuretic peptide activates CFTR in the shark rectal gland.
    Am J Physiol Cell Physiol. 2014 Feb 15;306(4):C343-53

  • Dekkers JF, Wiegerinck CL, De Jonge HR, Bronsveld I, Janssens HM, De Winter-De Groot KM, Bijvelds MJC, Nieuwenhuis EES, Van den Brink S, Clevers H, Van der Ent CK, Middendorp S, Beekman JM.
    A functional CFTR assay using primary cystic fibrosis intestinal organoids.
    Nat Med. 2013 Jul;19(7):939-45.

  • Bijvelds MJ, Bot AG, Escher JC, de Jonge HR.
    Activation of intestinal Cl- secretion by lubiprostone requires the Cystic Fibrosis Transmembrane conductance Regulator. 
    Gastroenterology. 2009 Sep;137(3):976-85.