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R.A.F.M. Chamuleau MD PhD

Position
Associate Professor
Main activities
Research, Other
Specialisation
Hepatology
Focus of research

 Pathophysiology and treatment of severe liver failure.

Development of a bioartificial liver charged with human liver cells able to support severe liver patients either to transplantation or recovery of the diseased liver.

Study of the mechanisms of liver regeneration and the influence of the bioartificial liver on it.

Development of a prognostic index to predict the course of acute liver failure.

Search for specific breathprints of exhaled air by eNose in patients with liver disease.

Key publications
  • Poyck Paul P. C., Hoekstra Ruurdtje, Chhatta Aniska, ten Bloemendaal Lysbeth, van Wijk Albert C. W. A., Galavotti Daniele, van Gulik Thomas M., Chamuleau Robert A. F. M. Time-related analysis of metabolic liver functions, cellular morphology, and gene expression of hepatocytes cultured in the bioartificial liver of the Academic Medical Center in Amsterdam (AMC-BAL) Tissue engineering 2007;13 (6):1235-1246 [PubMed]
  • Wlodzimirow Kama A., Eslami Saeid, Abu-Hanna Ameen, Nieuwoudt Martin, Chamuleau Robert A. F. M. A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality Liver international 2013;33 (1):40-52 [PubMed]
  • Wlodzimirow Kama, Abu-Hanna Ameen, Chamuleau Robert A. F. M. Acute-on-chronic liver failure - its definition remains unclear Journal of hepatology 2013;59 (1):190-191 [PubMed]
  • Hoekstra Ruurdtje, Nibourg Geert A. A., van der Hoeven Tessa V., Ackermans Mariëtte T., Hakvoort Theodorus B. M., van Gulik Thomas M., Lamers Wouter H., Elferink Ronald P. Oude, Chamuleau Robert A. F. M. The HepaRG cell line is suitable for bioartificial liver application international journal of biochemistry & cell biology 2011;43 (10):1483-1489 [PubMed]
  • Hoekstra Ruurdtje, Nibourg Geert A. A., van der Hoeven Tessa V., Plomer Gabrielle, Seppen Jurgen, Ackermans Mariëtte T., Camus Sandrine, Kulik Wim, van Gulik Thomas M., Elferink Ronald P. Oude, Chamuleau Robert A. F. M. Phase 1 and phase 2 drug metabolism and bile acid production of HepaRG cells in a bioartificial liver in absence of dimethyl sulfoxide Drug metabolism and disposition: the biological fate of chemicals 2013;41 (3):562-567 [PubMed]
  • Wlodzimirow Kama A., Eslami Saeid, Abu-Hanna Ameen, Nieuwoudt Martin, Chamuleau Robert A. F. M. Acute liver failure: What is it? Hepatology (Baltimore, Md.) 2012;55 (4):1306-1307 [PubMed]
All Publications
Curriculum Vitae


CURRICULUM VITAE

Name: Robert A.F.M. Chamuleau, MD, PhD
Birth date: 11-November 1941
Birth place: Maastricht, the Netherlands
Citizenship: Dutch
Home address: Koningin Emmalaan 11, 1405 CJ Bussum, the Netherlands
Home phone: 31- (0)35-6943167
Mobile: 06-50565552

Business address: Tytgat Institute for Liver and Intestinal Research, S-2, room 162
Academic Medical Center, University of Am¬sterdam,
Meibergdreef 69-71
1105 BK, Amsterdam, the Netherlands

Business phone: 31-(0)20-5665405
Business fax : 31-(0)20-5669190
Email: r.a.chamuleau@amc.uva.nl


EDUCATION and TRAINING
UNDERGRADUATE
1954-1960 Gymnasium beta, Stanislascollege, Delft

GRADUATE
1960-1968 Graduate as MD : Medical School, University of Amster¬dam.
1971 Graduate as PhD: B.C.P. Jansen Institute, Department of Bio¬chemis¬try, Uni¬versity of Am¬ster¬dam. Promotor: Prof J.M. Tager

APPOINTMENTS and POSITIONS

1963-1968 Research Assistant, Dept of Biochemistry, University of Amsterdam
1968-1971 Research Fellow, Dept of Biochemistry, University of Amsterdam.
1971-1972 Military Service, Central Laboratory Red Cross Bloo¬dtransfusion Service, Amsterdam.
1972-1974 Residency, Medicine, Municipal Hospital, Arnhem, The Nether¬lands.
1974-1976 Residency, Medicine, Academic Hospital, University of Amster¬dam.
1976 Registered in Internal Medicine
1976-1978 Chef de Clinique General Medicine, Dept Internal Medicine, Academic Hospital, Binnengast¬huis, University of Amsterdam.
1978-1981 Assistant Professor, Experimental Internal Medicine, Wilhelmina Gasthuis, University of Amsterdam.
1981-1996 Associate Professor, Dept of Experimental In¬ternal Medicine, Academic Medical Center, Uni¬versity of Amsterdam.
1990-1996 Acting Head, Laboratory of Experimental Medici¬ne, Academic Medical Center, University of Amsterdam.
1997-1998 TMR Marie Curie Research Training Grant, European Community
1996-2006 Associate Professor, internist-hepatologist, Dept of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam
2001- CSO Hep-Art Medical Devices BV
2006- Group leader research group bioartificial liver, Tytgat Institute for Liver and Intestinal research

MEMBERSHIPS in PROFESSIONAL and SCIENTIFIC SOCIETIES
1. Dutch Society of Internal Medicine
2. Dutch Society of Hepatology
3. European Society for Artificial Organs (ESAO)
4. European Association of the Study of the Liver (EASL)

REVIEWER FOR MEDICAL JOURNALS:
The Lancet
Journal of Hepatology
Hepato-Gastroenterology
Cell Transplantation
Liver International
World Journal Gastrointestinal Surgery
Ned Tijdschrift voor Geneeskunde

PROFESSIONAL ACTIVITIES

University teaching
Lectures in Hepatology, undergraduate biology students University of Amsterdam
Postgraduate courses Hepatology Academic Medical Center, University of Amsterdam
Summerschool University of Utrecht


DOCTORAL THESIS SUPERVISION

1978 R.B. Dinkelaar, Erythropoietin, University of Amsterdam
1982 HWM de Koning, Encapsulated sorbents for artificial liver support ,Technical University, Enschede, The Netherlands
1988 NEP Deutz, Pathophysiological aspects of acute hepatic encephalopathy in the rat. University of Amsterdam
1988 M.Sinaasappel, Het galzuurmetabolisme tijdens cholestase bij het jonge kind, University of Amsterdam
1989 AA de Graaf, Development of methods for quantitative in vivo NMR and their application to the study of hepatic encephalopathy in the brain, Technical University Delft, The Netherlands
1991 DC Aronson, Extrahepatic cholestasis in the rat: an experimental approach to biliary atresia, University of Amsterdam
1991 DK Bosman, Pathophysiology and therapy of hepatic encephalopathy. University of Amsterdam
1994 GTM Wagenaar, Regulation of gene expression and function of the liver in vivo, University of Amsterdam
1996 B. Vogels, Experimental hepatic encephalopathy: a central role of ammonia and portacaval shunting? University of Amsterdam
1996 A. Tiggelman, Liver fibrosis: a study on the role of alfa2 macroglobulin and liver (myo)fibroblasts. University of Amsterdam
1997 Chuan-Ging Wu, Identification of genes differentially expressed in hepatocellular carcinoma. University of Amsterdam
1998 F. ter Borg, HBeAg-negative hepatitis B, University of Amsterdam
1998 H. Meyer, Chronic hepatic encephalopathy: studies into the pathogenesis and treatment in the dog, University Utrecht
1998 L. Flendrig, Development of a novel bioartificial liver. University of Amsterdam
2003 M. Sosef, Experimental treatment modalities for liver failure, University of Amsterdam
2004 M-P van de Kerkhove, Optimization and clinical application of the AMC-Bioartificial liver, University of Amsterdam, the Netherlands
2007 P.P.C. Poyck, Study towards the implementation of a human liver cell line for application in the AMC bioartificial liver, University of Amsterdam, the Netherlands
2007 T. Deurholt, Development of an immortalised human hepatocyten cell line for the AMC bio-artificial liver. University of Amsterdam
2012 G. Nibourg, Human Liver Cell Lines for the AMC-Bioartificial Liver, University of Amsterdam

RESEARCH GRANTS OBTAINED ( 1995-2012, Total about 9 million euro)

MLDS L. Flendrig
STW H. de Koning
STW M-P van de Kerkhove/ R. Hoekstra
STW A. van Wijk/ M. Huisman
European Commission R. Hoekstra/T. Deurholt
MLDS P. Poyck
EU (Balance) R. Hoekstra/ M. van Wenum
HepArt Med Dev B.V. R. Hoekstra
Biopartner and SKE R. Hoekstra

CURRENT RESEARCH INTERESTS
Development and clinical application of a bio-artificial liver
Development of an immortalised human liver cell line
Liver regeneration
Hepatic Encephalopathy


PUBLICATIONS

> 200 papers in international peer reviewed journals.
7 key publications are:

1. Meijer AJ, Lamers WH, Chamu¬leau RAFM. Nitrogen metabolism and ornithine cycle function. Physiol Reviews 1990; 70: 701-748.
2. Bosman DK, van den Buijs CACG, de Haan JG, Maas MAW, Chamuleau RAFM.
The effects of benzodiazepine recep¬tor antagonists and partial inverse agonists on acute hepatic encephalopathy in the rat. Gastroenterology 1991; 101: 772-781.
3. Flendrig LM., la Soe JW., Jorning GGA., Steenbeek A., Ladiges NCJJ., te Velde AA., Chamuleau RAFM.In vitro evaluation of a novel bioartificial liver system based on a spirally nonwoven polyester matrix for high density hepatocyte culture as small aggregates. J Hepatol 1997; 26:1379-1392
4. Ter Borg F. ten Kate FJW, Cuypers HTM , Leentvaar-Kuipers A, Wertheim-van Dillen PME, Honkoop P, Rasch MC, deMan RA, van Hattum J, Chamuleau RAFM, , Reesink HW. Jones EA. The relationship between laboratory test results and histological hepatitis activity in HBsAg positive, anti HBe positive individuals. The Lancet 1998 , 351; 1914-1918.
5. Van der Vliet HN, Groenink Sammels M, Leegwater ACJ, Levels JHM, Reitsma PH, Boers W, Chamuleau RAFM. Apolipoprotein A-V. A novel apolipoprotein associated with an early phase of liver regeneration. J Biol Chem 2001;276:44512-44520.
6. Maarten-Paul van de Kerkhove, Ernesto Di Florio, Vincenzo Scuderi, Antonio Mancini, Antonello Belli, Adele Bracco, Mario Dauri, Giuseppe Tisone, Giuseppe Di Nicuolo, Pietro Amoroso, Alessandro Spadari, Guerino Lombardi, Ruurdtje Hoekstra, Fulvio Calise, Robert A.F.M. Chamuleau . Phase I clinical trial with the AMC Bioartificial liver. Int J Artif Organs, 2002; 25: 950-959
7. Geert A.A. Nibourg, RAFM Chamuleau, TV van der Hoeven et al. Liver progenitor cell line HepaRG differentiated in a bioartificial liver effectively supplies liver support to rats with acute live failure. PlosOne 2012; 7(6): e38778

 

 

Research programmes

R. Hoekstra PhD (Bioartificial Liver)

Prof. R.P.J. Oude Elferink PhD (Hepatic metabolism and transport processes)

R.A.F.M. Chamuleau MD PhD (Optimalization of the AMC Bioartificial liver (AMC-BAL) charged with HepaRG cells to bridge patients with severe liver failure to transplantation or own regeneration)

Acronyme: BALANCE

In BALANCE, the companies Hep-Art, Pharmacell and BioPredic join forces with academic partners Amsterdam Medical Centre and University of Edinburgh to offer Acute Liver Failure (ALF) patients a bioartificial liver-support system for bridging the waiting period for liver transplantation or recovery of the diseased liver.
ALF is a highly lethal disorder and liver transplantation is the only life-saving therapy. However, limited availability of donor livers severely reduces its impact. A bioartificial liver (BAL) may support ALF patients by temporary and extracorporeal treatment of their plasma through a bioreactor with functional human liver cells.
The central objective of BALANCE is to develop a GMP certified BAL that executes the three key liver functions for a clinically relevant period in ALF and to reach proof of safety and feasibility. What makes the HepaRG-BAL extremely potent is the unique combination of an ideal liver cell ecosystem and the introduction of the HepaRG cell line which is the only human cell line in the world that approaches human liver in its functionality.
A two-staged approach will be adopted. Stage I is designed for in-vitro optimisation of the BAL and the human cell line and stage II comprises of the ex-vivo activities in which the optimized and upscaled BAL is tested and validated in pigs (controlled study) and humans with ALF (phase I/IIa clinical study).
BALANCE will give birth to three main results: an optimised and validated BAL, a GMP manufacturing process and a GMP grade and stable human liver cell line. Hep-Art will further pursue clinical development of the BAL towards EMA registration and marketing together with a large industrial partner. Pharmacell will exploit the GMP manufacturing process for production of the trial and commercial material. BioPredic will further exploit the GMP-graded HepaRG cells. Last but not least, BALANCE will strengthen the European competitive advantage in the field of bioartificial organs.
 

Postdocs
R. Hoekstra PhD
V.A. van der Mark

Others
E.J. Hendriks BEng