Andreas Bikfalvi, M.D, Ph.D.
Director of Research Department
BIOSKETCH

I was born in Hungary and raised in Germany, and I have French and German citizenship. I am a trained M.D., Ph.D. and obtained my Medical Degree at the University of Bretagne Occidentale (Brest, Brittany, France) and carried out my residency in Haematology and Oncology with Professor Helmut Loeffler at the Department of internal medicine at the University of Kiel (Germany). I pursued my career with a Ph.D. at INSERM Unit 150 in Paris (Director: Professor Jacques Caen, Ph.D. supervisor: Professor Gerard Tobelem) followed by a first post-doctoral Fellowship in the laboratory of Dr Yves Courtois (INSERM) in Paris. During my Ph.D. training, I became interested in growth factor and vascular biology, where I focused on several aspects of the biology of fibroblast growth factors (FGF) in relation to the regulation of the endothelial cell phenotype. I also studied the interaction of FGF with hematopoietic cells. I showed that FGFs are important hematopoietic factors that promote megakaryocytopoiesis by regulating interleukin-6 expression (1,2).

In 1991, I joined, as a post-doctoral fellow, the laboratory of Professor Daniel B. Rifkin at New York University Medical Centre where I tackled the problem of the mechanisms of action of the different molecular forms of Fibroblast Growth Factor-2 (FGF-2). This was a very difficult task since FGF-2 exists as both high molecular weight (HMW) or low molecular weight forms (LMW) and which do not have classical motifs for their release through the endoplasmic reticulum / Golgi pathway. I could clearly show that HMW FGF-2 induces unique phenotypes by intracellular receptor-independent mechanisms, whereas LMW FGF-2 is released, activates tyrosine kinase receptors and regulates, in an autocrine fashion, mainly cell migration (3). This work constitutes now a cornerstone in the biology of the molecular forms of FGF since it has allowed the identification and cloning of transcription factors that associate with intracellular FGF.

After my post-doctoral Fellowship, I joined, in 1995, the laboratory of Professor Denis Barritault in Paris as a senior investigator of the National Scientific Research Centre (CNRS). I then joined, in the same year, the University of Bordeaux I as a Professor of Cell and Molecular Biology. After my arrival, I had set-up a new laboratory (Growth Factor and Cell Differentiation Laboratory, LFCDC which became the “Molecular Angiogenesis Laboratory” and which is now the “Angiogenesis and Tumor Microenvironment Laboratory”), which focused on the molecular aspects of vascular and tumor development and its application towards therapy. This laboratory is in fact a unit (department) which has several PIs and research teams. The laboratory is, since 2001, affiliated with the French National Institute for Scientific Research and Health (INSERM EMI 0113, INSERM U920, now INSERM U 1029) and directed by me.

 Within the last 20 years, the research of my group was centered on the regulation of tumor angiogenesis and tumor cell invasion. I investigated the role of fibroblast growth factors (FGF) signalling in the invasion and angiogenesis of solid tumors. I clearly showed that FGF ligands provide a double signal(4). One is directly controlling cell growth whereas the other is responsible for the neovascular response. Using targeted expression of dominant-negative FGF receptors, I clearly demonstrated that FGF signalling is involved in the vascular development in the choroid and the retina(5,6). Furthermore, I demonstrated that tumor angiogenesis in the eye is severely impaired in mice with ocular tumors in which FGF activity is inhibited(7). This also applies to cerebral tumors. I also evidenced a new pathway for the induction of angiogenic growth factors that involves the endoplasmic reticulum stress response(8,9). I also studied the role of endogenous FGFs in lymphangiogenesis and demonstrated the involvement of FGFR3 in this process (10). In a series of systematic studies, I partially elucidated the mechanisms of angiogenesis inhibition and I performed studies related to translational research and examined the usefulness of angiogenesis inhibitors such as PF-4 or of a C-terminal fragment of matrix metalloproteinase-2, for the treatment of malignant diseases(11-18). I have developed a novel angiogenesis inhibitor named cyclic vascular endothelial cell inhibitor (cyclo VEGI) and characterized its anti-angiogenic activity(19). I also carried-out projects related to and the development of novel angiogenesis models and the identification of new molecules and targets/biomarkers for tumor angiogenesis and invasion. In this regard, we had in 2005 developed a new tumor angiogenesis model in the chick embryo and identified a set of genes regulated during the angiogenic switch(20,21). We have developed this model into a discovery tool for cancer research (metabolomic profiling, prognostic factors, biomarkers, identification etc.) (22-30). We were/are also focusing our research on new variant of the CXCL4 chemokine named CXCL4L1 and on the role of the unfolded protein response (UPR) in tumor angiogenesis and invasion (31-33, 8-9). I have also elucidated some of the biological roles of the lymphatic marker Lyve-1 and studied its interactions with FGFs (34). I have, furthermore, published on extra-vascular functions of VEGF and evidenced its role in spinal motor-neuron development and network establishment (35). My recent activities are related to large-scale approaches and systems biology related to renal cell carcinoma and glioma including mathematical modelling. Using these approaches, we have recently identified new hallmarks of glioma progression (36). Furthermore, we have recently modelled the metastatic process in the lung through mathematical modelling (37). Finally, my work focused also on the CXCR3 receptor and my team has elucidated the role of CXCR3A in pancreatic adenocarcinoma development and glioblastoma invasion as well as its mechanism of action and trafficking (38,39). Furthermore, we have evidence unique properties at a structural level between CXCR3A and CXCR3B upon receptor activation which explains the differences in signaling of both receptor isoforms (40). Finally, recent studies on the mechanisms of tumor cell invasion in brain tumors establishes thrombospondin-1’s function in tumor cell invasion. These results have been published recently (41).

I am holding the position of a full Professor of exceptional class of second degree which is the highest Academic position in France. I am/was a member of various evaluation committees such as the presidency of a HCERES (“Haut Comité d’Evaluation de la Recherche et de l’Enseignement Supérieur”) committee in February 2018 for the evaluation of scientific teams in France and the Commission Nationale N°2 of INSERM (CSS2) since 2017 (5 years term). I am a member of the scientific advisory board of the Luxembourg Institute of Health (LIH) since 2016.

I am heading a department of 37 peoples in Bordeaux, which comprises 4 research groups. Since my arrival in Bordeaux (end of 1995), I have raised more than 15 million Euros in funding. 

National and international recognition and diffusion

The scientific impact of our work has been increasingly recognized.

I was a senior member of the “Institut Universitaire de France” (IUF) for 5 years (2011-2016, only 5 year appointments are allowed) which is a prestigious membership in France and covers all of the academia all over France (Science, Arts, Humanities). This is highly competitive and only distinguished senior Professors are eligible for membership.

Scientific impact is also documented by invitations to a number of international conferences (Institut Pasteur Euroconference on Angiogenesis, March 8-9, 2001; 2d symposium of the German Priority Research Program, Kloster Seeon, Sept 21-24, 2002; 5th Congress of the European Society of Neurooncology Meeting American Association for Cancer Research 2003 meeting, Chicago  Oct 15-19 2003 ; British Society for Rhumatology april 20-23, 2004, Signal transduction 2004, Jan 25-31, Luxemburg ; 8èmeEntretien Jacques Cartier, Lyon, Dez 5-6 2005; European Society of Medical Oncology (ESMO) Istanbul, Sept 29-Oct 3 2006; National Cancer Resarch Institute Conference Oct 5-8 Birmingham, 2007; Ramón Areces Foundation on the 12th and 13th of  November 2008, Málaga (Spain); Monte Verità conference on tumor-host interaction and angiogenesis, Ascona, Oct 31-Nov 4, 2010; Biochemical Society Meeting ‘Advances in the cellular and molecular biology of angiogenesis’, Birmingham, 27—29 June 2011 ; Brain tumor 2012-from biology to therapy, Warsaw, may 28-30 2012; Session chair International Vascular Biology Meeting, June 2018 in Helsinki, Finland). I have been rmore recently a member of the King Faysal International Prize Committee in Science (BIOLOGY, Riyadh, jan 14-16, 2012).I have also organized a number of scientific meetings during the last 10 years, including 8 international angiogenesis conferences with the European School of Hematology (ESH). I was a member of the scientific committee of ESH for over 10 years. Furthermore, I am member of the Editorial board of “Angiogenesis”, an associated editor of “BMC Cancer” and “BMC Research Notes” and I was a member of the American Society of Biochemistry and Molecular Biology (ASBMB). I have been the President of the French Angiogenesis Research Network between 1996-2007 (now become the French Angiogenesis Society) and the current secretary of the society. I have also edited with Springer Verlag an Encyclopeadia of Vascular Biology and Pathology. I have also written two books. The first was entitled “Une Brève Histoire du Vaisseau Sanguin et Lymphatique” and has been published in spring 2016 (INSERM-EDP Science Co-edition). This book received in 2017 the Jean-René Cruchet Prize from the “Académie Nationale des Sciences, Belles Lettres et Arts”.  I, furthermore, rewrote an English version of the book and updated it. This book (“A brief History of Blood and Lymphatic Vessels”) has been recently published by Springer Verlag (published April 2018). I have received several recognitions and awards (see CV).

I have been a member of EU consortia (STROMA project 7 PCRDT) and I am the coordinator of a recently funded EU ERA-NET/Transcan project on low grade gliomas (“ Multi-parametric analysis of the evolution and progression of low grade glioma”, GliomaPRD project, http://www.transcanfp7.eu/index.php/abstract/glioma-prd.html).

Education of young researchers

 Over the last 15 years the research has involved the supervision of more than 10 post-doctoral fellows and 20 graduate or undergraduate students. Several post-doctoral fellows obtained a permanent position in the Academia and were successful in their research: Martin Hagedorn (PhD 2004 and post-doctorate) was recruited as an Assistant Professor at the university where he continued successfully his research. Benoit Rousseau (past PhD student and post doctorate) was recruited as the head of the animal A2 facility at the university Bordeaux. Gregor Auf (past post-doctoral fellow) who was first author of an important PNAS paper (Auf et al, PNAS 2010) went back to Germany to continue neurosurgical training. Most of the remaining post-doctoral fellows went for a second post-doctorate (Lior Zilberberg, Daniel Rifkin’s laboratory NYU Medical Center; Frederic Larrieu-Lahargue in Dean Lee’s Laboratory, Salt Lake City; Witold Kilarski, Melody Schwartz Laboratory, Lausanne now Chicago; Natalia Platonova, university of Milan; Alexandre Dubrac, Anne Eichmann’s laboratory, Yale University, USA; It is to emphasize that Alexandre Dubrac is highly successful and considered the best post-doctoral fellows of the Yale Cardiovascular Research Center. He has started an independent position as an Assistant Professor in Montreal (St Justine Research Center) in september 2018 where he will head his own laboratory. All of the graduate students have successfully defended their thesis.Thomas Daubon (post-doctoral fellow) is in the best position to be recruited either at INSERM or the CNRS this fall.

I have also established a strong interaction with the laboratory of Michel Tremblay (Goodman Cancer Center) and McGill university and 2 PhD students have participated and are participating in this interaction (Mathilde Poulet, PhD defense Dec 2017; Tiffanie Chouleur, first year PhD student). A “co-tutelle” (co-diploma) agreement has been established between McGill university and the university Bordeaux for Tiffanie Chouleur which is the first shared degree between both universities in the biomedical sciences.

Interaction with the Canadian Research Community

The interaction with Canada are spanning over the last 20 years.

In 2001, I have established an interaction with Pnina Brodt (McGill University) on several aspect of tumor cell invasion and angiogenesis. She visited my laboratory and I also travelled several times to Canada within this collaboration. My former assistant Patrick August spent 1 year in her laboratory where he was working on the role of proteases in angiogenesis and tumor invasion.

I had also an FRSQ travel exchange grant with Eric Chevet in 2004 who was a former assistant professor at Mc Gill university. The project was related to the role of the unfolded protein response on glioma angiogenesis and invasion.

During my several visits to Canada I met with Prof Michel Tremblay and we decided to develop projects together in 2012/13. First one of my technical assistants (Géraldine Miquel) spent 1 year in his laboratory. We next co-directed a PhD student (Mathilde Poulet) who defended successfully her PhD in  Dezember 2017. The PhD thesis combined the expertises of both laboratories, Angiogenesis (Bikfalvi) and phosphatases (Tremblay).

Based on this successful interaction, I promoted with Michel Tremblay the establishment of a joint PhD program between McGill University and Bordeaux University in the biomedical sciences. This program has been initiated in September 2017 with a first PhD student enrolled in this program (Tiffanie Chouleur) who will obtain a diploma from both universities. Another PhD student (not yet selected) will enrol the program by the end of this year.

References

  1. BikfalviA, Han ZC, Fuhrmann G. Blood. 1992 Oct 15;80(8):1905-13.
  2. BikfalviA, Han ZC. Leukemia. 1994 Mar;8(3):523-9.
  3. BikfalviA, Klein S, Pintucci G, Quarto N, Mignatti P, Rifkin DB. J Cell Biol. 1995 Apr;129(1):233-43.
  4. Auguste, P., Gursel, D. B., Lemiere, S., Reimers, D., Cuevas, P., Carceller, F., Di Santo, J. P., and Bikfalvi, A. (2001) Cancer Res61(4), 1717-1726
  5. Rousseau, B., Larrieu-Lahargue, F., Bikfalvi, A., and Javerzat, S. (2003) Exp Eye Res77(2), 147-156
  6. Rousseau, B., Dubayle, D., Sennlaub, F., Jeanny, J. C., Costet, P., Bikfalvi, A., and Javerzat, S. (2000) Exp Eye Res71(4), 395-404
  7. Rousseau, B., Larrieu-Lahargue, F., Javerzat, S., Guilhem-Ducleon, F., Beermann, F., and Bikfalvi, A. (2004) Cancer Res64(7), 2490-2495
  8. Auf, G., Jabouille, A., Guerit, S., Pineau, R., Delugin, M., Bouchecareilh, M., Magnin, N., Favereaux, A., Maitre, M., Gaiser, T., von Deimling, A., Czabanka, M., Vajkoczy, P., Chevet, E., Bikfalvi, A., and Moenner, M. Proc Natl Acad Sci U S A107(35), 15553-15558
  9. Drogat, B., Auguste, P., Nguyen, D. T., Bouchecareilh, M., Pineau, R., Nalbantoglu, J., Kaufman, R. J., Chevet, E., Bikfalvi, A., and Moenner, M. (2007) Cancer Res67(14), 6700-6707
  10. Shin, J. W., Min, M., Larrieu-Lahargue, F., Canron, X., Kunstfeld, R., Nguyen, L., Henderson, J. E., Bikfalvi, A., Detmar, M., and Hong, Y. K. (2006) Mol Biol Cell17(2), 576-584
  11. Ragona, L., Tomaselli, S., Quemener, C., Zetta, L., and Bikfalvi, A. (2009) Biochem Biophys Res Commun382(1), 26-29
  12. Lozano, R. M., Redondo-Horcajo, M., Jimenez, M. A., Zilberberg, L., Cuevas, P., Bikfalvi, A., Rico, M., and Gimenez-Gallego, G. (2001) J Biol Chem276(38), 35723-35734
  13. Hagedorn, M., Zilberberg, L., Lozano, R. M., Cuevas, P., Canron, X., Redondo-Horcajo, M., Gimenez-Gallego, G., and Bikfalvi, A. (2001) FASEB J15(3), 550-552
  14. Bello, L., Carrabba, G., Giussani, C., Lucini, V., Cerutti, F., Scaglione, F., Landre, J., Pluderi, M., Tomei, G., Villani, R., Carroll, R. S., Black, P. M., and Bikfalvi, A. (2001) Cancer Res61(20), 7501-7506
  15. Bello, L., Giussani, C., Carrabba, G., Pluderi, M., Lucini, V., Pannacci, M., Caronzolo, D., Tomei, G., Villani, R., Scaglione, F., Carroll, R. S., and Bikfalvi, A. (2002) Clin Cancer Res8(11), 3539-3548
  16. Hagedorn, M., Zilberberg, L., Wilting, J., Canron, X., Carrabba, G., Giussani, C., Pluderi, M., Bello, L., and Bikfalvi, A. (2002) Cancer Res62(23), 6884-6890
  17. Giussani, C., Carrabba, G., Pluderi, M., Lucini, V., Pannacci, M., Caronzolo, D., Costa, F., Minotti, M., Tomei, G., Villani, R., Carroll, R. S., Bikfalvi, A., and Bello, L. (2003) Cancer Res63(10), 2499-2505
  18. Bello, L., Lucini, V., Costa, F., Pluderi, M., Giussani, C., Acerbi, F., Carrabba, G., Pannacci, M., Caronzolo, D., Grosso, S., Shinkaruk, S., Colleoni, F., Canron, X., Tomei, G., Deleris, G., and Bikfalvi, A. (2004) Clin Cancer Res10(13), 4527-4537
  19. Zilberberg, L., Shinkaruk, S., Lequin, O., Rousseau, B., Hagedorn, M., Costa, F., Caronzolo, D., Balke, M., Canron, X., Convert, O., Lain, G., Gionnet, K., Goncalves, M., Bayle, M., Bello, L., Chassaing, G., Deleris, G., and Bikfalvi, A. (2003) J Biol Chem278(37), 35564-35573
  20. Hagedorn, M., Balke, M., Schmidt, A., Bloch, W., Kurz, H., Javerzat, S., Rousseau, B., Wilting, J., and Bikfalvi, A. (2004) Dev Dyn230(1), 23-33
  21. Hagedorn, M., Javerzat, S., Gilges, D., Meyre, A., de Lafarge, B., Eichmann, A., and Bikfalvi, A. (2005) Proc Natl Acad Sci U S A102(5), 1643-1648
  22. Cavill, R., Sidhu, J. K., Kilarski, W., Javerzat, S., Hagedorn, M., Ebbels, T. M., Bikfalvi, A., and Keun, H. C. J Proteome Res9(6), 3126-3134
  23. Dumartin, L., Quemener, C., Laklai, H., Herbert, J., Bicknell, R., Bousquet, C., Pyronnet, S., Castronovo, V., Schilling, M. K., Bikfalvi, A., and Hagedorn, M. Gastroenterology2010 Apr;138(4):1595-606,
  24. Javerzat, S., Franco, M., Herbert, J., Platonova, N., Peille, A. L., Pantesco, V., De Vos, J., Assou, S., Bicknell, R., Bikfalvi, A., and Hagedorn, M. (2009) PLoS One4(11), e7856
  25. Soulet, F., Kilarski, W. W., Antczak, P., Herbert, J., Bicknell, R., Falciani, F., and Bikfalvi, A. BMC Genomics11, 495
  26. Saidi, A., Hagedorn, M., Allain, N., Verpelli, C., Sala, C., Bello, L., Bikfalvi, A., and Javerzat, S. (2009) Int J Cancer125(5), 1054-1064
  27. Saidi, A., Javerzat, S., Bellahcene, A., De Vos, J., Bello, L., Castronovo, V., Deprez, M., Loiseau, H., Bikfalvi, A., and Hagedorn, M. (2008) Int J Cancer122(10), 2187-2198
  28. Soulet F, Kilarski WW, Roux-Dalvai F, Herbert JM, Sacewicz I, Mouton-Barbosa E, Bicknell R, Lalor P, Monsarrat B, Bikfalvi Mol Cell Proteomics. 2013 Aug;12(8):2293-312.
  29. Fergelot P, Bernhard JC, Soulet F, Kilarski WW, Léon C, Courtois N, Deminière C, Herbert JM, Antczak P, Falciani F, Rioux-Leclercq N, Patard JJ, Ferrière JM, Ravaud A, Hagedorn M, Bikfalvi Angiogenesis. 2013 Jan;16(1):181-94.
  30. Kilarski WW, Herbert J, Bikfalvi Methods Mol Biol. 2018;1722:31-56
  31. Lasagni, L., Grepin, R., Mazzinghi, B., Lazzeri, E., Meini, C., Sagrinati, C., Liotta, F., Frosali, F., Ronconi, E., Alain-Courtois, N., Ballerini, L., Netti, G. S., Maggi, E., Annunziato, F., Serio, M., Romagnani, S., Bikfalvi, A., and Romagnani, P. (2007) Blood109(10), 4127-4134
  32. Dubrac, A., Quemener, C., Lacazette, E., Lopez, F., Zanibellato, C., Wu, W. G., Bikfalvi, A., and Prats, H. Blood116(22), 4703-4711
  33. Kuo JH, Chen YP, Liu JS, Dubrac A, Quemener C, Prats H, BikfalviA, Wu WG, Sue SC. J Biol Chem. 2013 May 10;288(19):13522-33.
  34. Platonova N, Miquel G, Regenfuss B, Taouji S, Cursiefen C, Chevet E, Bikfalvi Blood. 2013 Feb 14;121(7):1229-37
  35. Guérit S, Allain AE, Léon C, Cazenave W, Ferrara N, Branchereau P, Bikfalvi Dev Neurobiol. 2014 Nov;74(11):1110-22.
  36. Clarke K, Daubon T, Turan N, Soulet F, Mohd Zahari M, Ryan KR, Durant S, He S, Herbert J, Ankers J, Heath JK, Bjerkvig R, Bicknell R, Hotchin NA, BikfalviA, Falciani F. PLoS Genet. 2015 Jul 1;11(7):e1005325.
  37. Baratchart E, Benzekry S, BikfalviA, ColinT, CooleyL, PineauR, RibotE, SautO, Souleyreau W. PlosComp Biol 2015 Nov 23;11(11):e1004626 Benzekry, A. Bikfalvi, T. Colin senior authors)
  38. Quemener C, Baud J, Boyé K, Dubrac A, Billottet C, Soulet F, Darlot F, Dumartin L, Sire M, Grepin R, Daubon T, Rayne F, Wodrich H, Couvelard A, Pineau R, Schilling M, Castronovo V, Sue SC, Clarke K, Lomri A, Khatib AM, Hagedorn M, Prats H, BikfalviCancer Res. 2016 Nov 15;76(22):6507-6519.
  39. Boyé K, Pujol N, D Alves I, Chen YP, Daubon T, Lee YZ, Dedieu S, Constantin M, Bello L, Rossi M, Bjerkvig R, Sue SC, BikfalviA, Billottet C.Nat Commun. 2017 Nov 17;8(1):1571
  40. Boyé K, Billottet C, Pujol N, Alves ID, Bikfalvi A.Sci Rep. 2017 Sep 6;7(1):10703.
  41. Daubon T, Léon C, Clarke K, Andrique L, Salabert L, Darbo E, Pineau R, Guérit S, Maitre M, Dedieu S, Jeanne A, Bailly S, Feige JJ, Miletic H, Rossi M, Bello L, Falciani F, Bjerkvig R, Bikfalvi A.Nat Commun. 2019 Mar 8;10(1):1146.

Andreas Bikfalvi

Professional skills

Expert in Cancer and Vascular Biology
Philosophy of Science
Jazz Musicianship (Guitar)