Category: About The Iccns

Categories
About The Iccns

President

Bernard Perbal, D.Sc., LL.D

Degrees and Positions

  • Diploma of Advanced Studies (DEA), “Enzymology” (1968)
  • Doctorate of Sciences (D. Sc.) Biochemistry and Genetics. University of Paris (1974).
  • Post-doctoral fellow Western Infirmary- Intitute of Virology, Glagow Scotland UK (1974-1975)
  • Invited Professor, UCLA, Dpt of Molecualr Biology and Immunology Los Angeles CA USA (1980-1982)
  • Founder and Director of the Viral and Molecular Oncology Laboratory at the Curie Institute CNRS
  • Research Director (1982-1988)
  • Full Professor of Biotechnologies, Molecular Genetics and Biochemistry, Molecular Pathology
  • (1988-2007) University of Paris VI P.M. Curie, and Paris 7, D. Diderot.
  • Associate Principal Scientist – Open Research Dpt. L’Oréal USA Clark NJ (2008-2010)
  • Senior Research Associate Scientific Direction, L’Oréal Clichy France (2010-2011)
  • Professional Master’s Degree: Economy, Law and Finance. Option Law of Intellectual Property and New technologies. University of Nice, (2011-2012)
  • Law Doctorate (LL.D.): Genetic Personal data and Self ownership. University of Nice, (2018)
  • Attorney at Law. Oath-taking (2021) – Court of Appeal Aix en Provence – Bar of Marseille France.
  • Couple and Sexology therapist (2023)

Societies

  • American Association for Cancer Research
  • American Association for the Advancement of Science
  • American Society for Microbiology, Molecular Biology Society
  • American Society for Virology
  • Founder of the International CCN Society

Awards

  • 1965 Laureate of the Concours Général de Sciences Naturelles (France)
  • 1990 Laureate of the French Académie des Sciences (Prix G. Rousseau)
  • 1992 Laureate of the Académie des Sciences (Grand Prix INSERM et Académie des Sciences )
  • 1992 Laureate of the French Ligue Nationale Contre le Cancer (Prix S. Dumonteil)
  • 2012 International CCN Society Award

Books and Reports

  • A Practical Guide to Molecular Cloning (Wiley, 1988, 1992)
  • Molecular Biology of Polyomaviruses and Herpes viruses (Wiley, 1982)
  • Clonage Moléculaire : Un Guide Pratique (Vigot, 1989)
  • CCN Proteins: A New Family of Cell Growth and Differentiation Regulators (Editor, Imperial College Press, 2005)
  • CCN Proteins in Health and Disease (Editor, Springer, 2010)
  • Focus on the patentability of computer programs (2014) J Cell Commun Signal.8(1):67-70

Editorial Board

  • Founder and former Editor in Chief of Methods in Molecular and Cellular Biology (Wiley, New York, 1989)
  • Founder and Editor in Chief of “Cell Communication and signaling” (2003) a former publication of BMC
  • Founder and Editor in Chief of “Journal of Cell Communication and signaling” published by Springer (2007-2023) and by Wiley from Januaray 2024

Research Themes

The studies performed in the laboratory of Viral Oncology that I created in 1982 were aimed at understanding :
• the molecular basis for the Myeloblastosis Associated Virus (MAV) tumorigenic potential.
• the biochemical properties, mode of action and biological role of the CCN3 (NOV) protein in normal and pathological conditions with a particular emphasis to the potential use of the CCN3 protein as a new tool for molecular medicine
The MAV strains usually induce osteopetrosis, lymphomas, and nephroblastomas in chicken (Perbal, 1995). MAV is the natural helper virus of Avian Myelobalstosis virus (AMV). Molecular cloning of a MAV strain inducing specifically nephroblastoma when injected in day-old chicken (Perbal 1985, Soret et al. 1985) allowed to establish that MAV-induced nephroblastoma represent a unique animal model for the Wilms’ tumor (Perbal 1994). The molecular cloning of MAV integration sites in the host genome, identified several genes whose viral induced alteration is associated to cancer development (Li et al. 2006). One of them, CCN3 was one of the three founding members of the CCN family of 6 proteins involved in the regulation of cell proliferation and differentiation in several normal and tumoral contexts (Joliot et al., 1992, Perbal , 2001).
Functionally bipartite, with members acting negatively or positively on cell communication and signaling, the CCN proteins are subject to complex fine tuning regulation from which stemmed the concept of their biological properties being based on a spatio-temporal combinatorial events model (Perbal . 2013, 2018, 2023)
Disregulation of the ccn3 gene expression and abnormal production, processing or localization of the CCN3 protein is associated to malignancy in several tumor cases. CCN3 detection in tumor samples is associated to a favorable outcome in several types of tumors and in some documented cases its expression is associated to metastatic potentiality of the tumor cells (Planque and Perbal 2003, Perbal 2003). The value of CCN3 as a prognostic marker has been established in the case of osteosarcomas (Perbal et al. 2008) and melanomas (Vallacchi et al. 2008). CCN3 is reducing the tumorigenic potential of glioblastomas, choriocarcinomas, Ewing’s tumors and melanomas. These observations set the stage for developing protocols for genetic therapy of these tumors.
Proteins and ligands interacting with CCN3 allow it to play its regulatory role in the control of cell attachement, spreading, proliferation and differentiation. After biologically active truncated CCN3 proteins with different sub cellular localization (Perbal 2004, Planque et al. 2006), were identified in our laboratory, several groups reported the existence of truncated and rearranged forms of other CCN proteins (Perbal et al. 2023). Since the nuclear CCN3 proteins detected in cancer cells have been shown to regulate transcription, we have proposed that a balanced production of secreted CCN3 protein with anti-proliferative activity and nuclear CCN3 protein with pro-proliferative and oncogenic activities is required for the spatio temporal combinatorial events control of its biological activities (Perbal et al 2023).
Recent Orientations
My interest in the molecular basis of genetic diseases which stemmed from my early retrovirology studies, led me to undertake investigations in the legal aspects related to genetic information protection of human. Further to the COVID pandemic and interrogations expressed by the public, I became interested in social approches of medical diseases and the combination power of my scientific and legal activities culminated in my certification as a couple therapist and sexologist.

Selected Publications in the field of cell communication and signaling

Full list available on
PubMed https://pubmed.ncbi.nlm.nih.gov/?term=perbal+b

Perbal B, Perbal M, Perbal A. Cooperation is
the key: the CCN biological system as a gate to high complex protein
superfamilies’ signaling.J Cell Commun Signal. 2023 Jun;17(2):233-253. doi:
10.1007/s12079-023-00749-8.PMID: 37166690Free PMC article. 2

Perbal B.J Time has come to address the
spatiotemporal combinatorial model for CCN proteins biological activitites by
spatial transcriptomics and genome wide association studies. Cell Commun Signal. 2023 Mar;17(1):1-3.

Kubota S, Kawaki H, Perbal
B, Takigawa M, Kawata K, Hattori T, Nishida T. Do not overwork:
cellular communication network factor 3 for life in cartilage.J Cell Commun Signal. 2023 Jun;17(2):353-359.

Perbal B. The power of combined spatial
transcriptomics and genome wide association studies (GWAS) approaches to heritable prostate cancer. J Cell Commun Signal. 2023 Mar;17(1):5-6. doi:10.1007/s12079-023-00724-3.6

Yeger H, Perbal B. The CCN axis in cancer development and progression. J Cell Commun Signal. 2021Dec;15(4):491-517.

Perbal B.J Cell Commun Signal. 2019 Dec;13(4):437-439. doi: 10.1007/s12079-019-00543-5. CCN proteins are part of a
multilayer complex system: a working model.

Perbal B, Tweedie S, Bruford E.J The official unified nomenclature adopted by the HGNC calls for the use of the acronyms, CCN1-6, and discontinuation in the use of CYR61, CTGF, NOV and WISP 1-3 respectively.Cell Commun Signal. 2018 Dec;12(4):625-629. doi: 10.1007/s12079-018-0491-1. Epub 2018 Nov5.

Perbal B. The concept of the CCN protein family revisited: a
centralized coordination network. J Cell Commun Signal. 2018
Mar;12(1):3-12. doi: 10.1007/s12079-018-0455-5. Epub 2018 Feb 22.

Dombrowski Y, O’Hagan T, Dittmer M, Penalva R, Mayoral SR, Bankhead P, Fleville S,Eleftheriadis G, Zhao C, Naughton M, Hassan R, Moffat J, Falconer J, Boyd A,Hamilton P, Allen IV, Kissenpfennig A, Moynagh PN, Evergren E, Perbal B, Williams AC, Ingram RJ, Chan JR, Franklin RJM, Fitzgerald DC.Regulatory T cells promote myelin regeneration in the central nervous system Nat Neurosci. 2017
May;20(5):674-680. doi: 10.1038/nn.4528. Epub 2017 Mar 13.

Perbal B, Tweedie S, Bruford E The official unified nomenclature adopted by the HGNC calls for the use of the acronyms, CCN1-6, and discontinuation in the use of CYR61, CTGF, NOV and WISP 1-3 respectively. J Cell Commun Signal. 2018 Dec;12(4):625-629

Perbal B. The concept of the CCN protein family revisited: a centralized coordination network. J Cell Commun Signal. 2018 Mar;12(1):3-12.

Yeger H, Perbal B. CCN family of proteins: critical modulators of the tumor cell microenvironment. J Cell Commun Signal. 2016
Sep;10(3):229-240.

Zhang C, van der Voort D, Shi H, Zhang R, Qing Y, Hiraoka S, Takemoto M, Yokote K, Moxon JV, Norman P, Rittié L, Kuivaniemi H, Atkins GB, Gerson SL, Shi GP, Golledge J,
Dong N, Perbal B, Prosdocimo DA, Lin Z. Matricellular protein CCN3 mitigates abdominal aortic aneurysm. J Clin Invest. 2016 May 2;126(5):2012.

Perbal B CCN Proteins : A Centralized Communication System.
J Cell Commun Signal. 2013 Aug;7(3):169-77..May;180(5):1979-90.

Ouellet V, Tiedemann K, Mourskaia A, Fong JE, Tran-Thanh D, Amir E, Clemons M, Perbal B, Komarova SV, Siegel P. CCN3 impairs osteoblast and stimulates osteoclast differentiation to favor breast cancer metastasis to boneAm J Pathol 2011 May;178(5):2377-88

Rittié L,Perbal B,Castellot JJ, Orringer JS, Voorhees JJ, Fisher GJ Spatial-temporal modulation of CCN
proteins during wound healing in human skin in vivo J Cell Commun Signal. 2011 Mar;5(1):69-80

Lin Z, Natesan V, Shi H, Hamik A, Kawanami D, Hao C, Mahabaleshwar GH, Wang W, Jin ZG, Atkins GB, Firth SM, Rittié L, Perbal B, Jain MK A novel role of CCN3 in regulating endothelial inflammation. J Cell Commun Signal. 2010 Oct;4(3):141-53.

Perbal B, Lazar N, Zambelli D, Lopez-Guerrero JA, Llombart-Bosch A, Scotlandi K, Picci P. ‪Prognostic relevance of CCN3 in Ewing sarcoma. ‪Hum Pathol. 2009 Oct;40(10):1479-86. Epub 2009 Aug 19. ‪

Perbal B. ‪Alternative splicing of CCN mRNAs…. it has been upon us. ‪J Cell Commun Signal. 2009 Jun;3(2):153-7. Epub 2009
Apr 28.

 Holbourn KP, Acharya KR, Perbal B. ‪The CCN family of proteins: structure-function relationships. ‪Trends Biochem Sci. 2008
Oct;33(10):461-73. Epub 2008 Sep 11. ‪

 Kawaki H, Kubota S, Suzuki A, Lazar N, Yamada T, Matsumura T, Ohgawara T, Maeda T, Perbal B, Lyons KM,
Takigawa M. ‪ Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 shown by a comprehensive analysis of the CCN family proteins in cartilage. ‪J Bone Miner Res. 2008
Nov;23(11):1751-64. ‪

Yeger H, Perbal B. The CCN family of genes: a perspective on CCN biology and therapeutic potential. J Cell Commun Signal.
2008 Jun 21. [Epub ahead of print]

Perbal B, Zuntini M, Zambelli D, Serra M, Sciandra M, Cantiani L, Lucarelli E, Picci P, Scotlandi K. Prognostic
value of CCN3 in osteosarcoma. Clin Cancer Res. 2008 Feb 1;14(3):701-9.

Vallacchi V, Daniotti M, Ratti F, Di Stasi D, Deho P, De Filippo A, Tragni G, Balsari A, Carbone A, Rivoltini L, Parmiani G, Lazar N, Perbal B, Rodolfo M. CCN3/nephroblastoma overexpressed matricellular protein regulates integrin expression, adhesion, and dissemination in melanoma. Cancer Res. 2008 Feb 1;68(3):715-23. Erratum in: Cancer Res. 2008 Mar 15;68(6):2051.

Lazar N, Manara C, Navarro S, Bleau A-M, Llombart-Bosch A, Scotlandi K, Planque N, Perbal B. Domain-specific CCN3 antibodies asunique tools for structural and functional studies
J. Cell Commun Signal. 2007 Sep;1(2):91-102. Epub 2007 Sep 8.

Fukunaga-Kalabis M, Martinez G, Telson SM, Liu ZJ, Balint K, Juhasz I, Elder DE, Perbal B, Herlyn M.
Downregulation of CCN3 expression as a potential mechanism for melanoma progression. Oncogene. 2008 Apr 17;27(18):2552-60. Epub 2007 Oct 29.

van Roeyen CR, Eitner F, Scholl T, Boor P, Kunter U, Planque N, Grone HJ, Bleau AM, Perbal B, Ostendorf T, Floege J. CCN3 is a novel endogenous PDGF-regulated inhibitor of glomerular cell proliferation. Kidney Int. 2007 Oct 3; [Epub ahead of print]

Bleau AM, Planque N, Lazar N, Zambelli D, Ori A, Quan T, Fisher G, Scotlandi K, Perbal B. Antiproliferative activity of CCN3: Involvement of the C-terminal module and post-translational regulation. J Cell Biochem. 2007 Mar 5; [Epub ahead of print]

Perbal B. The CCN3 protein and cancer. Adv Exp Med Biol. 2006;587:23-40. Review.

Fukunaga-Kalabis M, Martinez G, Liu ZJ, Kalabis J, Mrass P, Weninger W, Firth SM, Planque N, Perbal B, Herlyn M. CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1. J Cell Biol. 2006 Nov 20;175(4):563-9. Epub 2006 Nov 13..

Perbal B. New insight into CCN3 interactions – Nuclear CCN3
: fact or fantasy? Cell Commun Signal. 2006 Aug 8;4:6.

McCallum L, Price S, Planque N, Perbal B, Pierce A, Whetton AD, Irvine AE. A novel mechanism for BCR-ABL action: stimulated secretion of CCN3 is involved in growth and differentiation regulation. Blood. 2006 Sep 1;108(5):1716-23. Epub 2006 May 2.

Planque N, Long Li C, Saule S, Bleau AM, Perbal B. Nuclear
addressing provides a clue for the transforming activity of amino-truncated CCN3 proteins. J Cell Biochem. 2006 Sep 1;99(1):105-16.

Perbal B. NOV story: the way to CCN3. Cell Commun Signal.
2006 Feb 20;4:3.

Benini S, Perbal B, Zambelli D, Colombo MP, Manara MC, Serra M, Parenza M, Martinez V, Picci P, Scotlandi K. In Ewing’s sarcoma CCN3(NOV) inhibits proliferation while promoting migration and invasion of the same cell type. Oncogene. 2005 Jun 23;24(27):4349-61.

Bleau AM, Planque N, Perbal B. CCN proteins and cancer: two
to tango. Front Biosci. 2005 May 1;10:998-1009.

Kyurkchiev S, Yeger H, Bleau AM, Perbal B. Potential
cellular conformations of the CCN3(NOV) protein. Cell Commun Signal. 2004 Sep 10;2(1):9.

Fu CT, Bechberger JF, Ozog MA, Perbal B, Naus CC.
CCN3 (NOV) interacts with connexin43 in C6 glioma cells: possible mechanism of connexin-mediated growth suppression. J Biol Chem. 2004 Aug 27;279(35):36943-50. Epub 2004 Jun 21.

Gellhaus A, Dong X, Propson S, Maass K, Klein-Hitpass L, Kibschull M, Traub O, Willecke K, Perbal B, Lye SJ, Winterhager E. Connexin43 interacts with NOV: a possible mechanism for negative regulation of cell growth in choriocarcinoma cells. J Biol Chem. 2004 Aug 27;279(35):36931-42. Epub 2004
Jun 4.

Katsube K, Chuai ML, Liu YC, Kabasawa Y, Takagi M, Perbal B, Sakamoto K. The expression of chicken NOV, a member of the CCN gene family, in early stage development. Brain Res Gene Expr Patterns. 2001 Aug;1(1):61-5.

Perbal B. CCN proteins : multifunctional signalling regulators. Lancet 2004 Jan;363(9) :62-64

Perbal B. Communication is the key. Cell Commun Signal.
2003 Oct 27;1(1):3.

Perbal B. The CCN3 (NOV) cell growth regulator: a new tool
for molecular medicine. Expert Rev Mol Diagn. 2003 Sep;3(5):597-604.

Planque N, Perbal B. A structural approach to the role of
CCN (CYR61/CTGF/NOV) proteins in tumourigenesis. Cancer Cell Int. 2003 Aug 22;3(1):15.

Li CL, Martinez V, He B, Lombet A, Perbal B. A role for
CCN3 (NOV) in calcium signalling. Mol Pathol. 2002 Aug;55(4):250-61.

Sakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, Li CL, Perbal B, Katsube K. The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway. J Biol Chem. 2002 Aug 16;277(33):29399-405. Epub 2002 Jun 05.

Manara MC, Perbal B, Benini S, Strammiello R, Cerisano V,
Perdichizzi S, Serra M, Astolfi A, Bertoni F, Alami J, Yeger H, Picci P, Scotlandi K. The expression of ccn3(nov) gene in musculoskeletal tumors. Am J Pathol. 2002 Mar;160(3):849-59.

Perbal B. Les protéines CCN : quand multimodulaire rime
avec multifonctionnel. Médecine-Sciences. 2002 Jun;18 :745-56

Thomopoulos GN, Kyurkchiev S, Perbal B. Immunocytochemical localization of NOVH protein and ultrastructural characteristics of NCI-H295R cells. J Submicrosc Cytol Pathol. 2001 Jul;33(3):251-60.

Gupta N, Wang H, McLeod TL, Naus CC, Kyurkchiev S, Advani S, Yu J, Perbal B, Weichselbaum RR. Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV).
Mol Pathol. 2001 Oct;54(5):293-9.

Maillard M, Cadot B, Ball RY, Sethia K, Edwards DR, Perbal B, Tatoud R. Differential expression of the ccn3 (nov) proto-oncogene in human prostate cell lines and tissues Mol Pathol. 2001 Aug;54(4):275-80

Su BY, Cai WQ, Zhang CG, Martinez V, Lombet A, Perbal B.
The expression of ccn3 (nov) RNA and protein in the rat central nervous system is developmentally regulated Mol Pathol 2001 Jun;54(3):184-91.

Perbal B. NOV (nephroblastoma overexpressed) and the CCN
family of genes: structural and functional issues. Mol Pathol. 2001
Apr;54(2):57-79. doi: 10.1136/mp.54.2.57

Joliot V, Martinerie C, Dambrine G, Plassiart G, Brisac M, Crochet J, Perbal B . Proviral rearrangements and overexpression of a newcellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas. Mol Cell Biol. 1992 Jan;12(1):10-21.