CV Science

claude Sardet PhD, DRCE CNRS, director of the Montpellier Cancer Research Institute (until 07/2022) IRCM U1194 (Inserm, University of Montpellier, Cancer Hospital CLCC-ICM)

Course and current status

Claude SARDET: Born: 13/02/1961 in Niort (79, France), French citizen.
Mail: claude.sardet@inserm.fr Tel: (33)467612584 (Office) (33)621110021 (Mobile)

CURRENT POSITION
• Directeur de Recherche CNRS (DRCE)
• Director of the Institut de Recherche en Cancérologie de Montpellier (IRCM U1194 Inserm, Université de Montpellier, ICM/CLCC cancer hospital of Montpellier) – first mandate 2015 -> 2020, second mandate 2021-2025, ongoing but will stop in july 2022 in the frame of a planed rotation    

EDUCATION
• 1983 Master of Engineering / INSA, Lyon, France.
• 1986 DEA, Mol. Pharmacology, University of Nice, France
• 1986 “Physiology course” Marine Biological Laboratory, Woods Hole, USA
• 1990 PhD Molecular Pharmacology, University of Nice, France
• 1997 HDR, University of Montpellier, France 

PROFESSIONAL CAREER
• 1983-85 Biologist of the 34th French Polar Expedition (EPF), Dumont D'Urville polar station, Antarctic.
• 1985-86 Research Assistant (IE) Fellow CNRS, Respiration Physiology, Cnrs (Y Le Maho's lab), Strasbourg, France
• 1986-89 Graduate Student, Centre de Biochimie, CNRS (J Pouyssegur's lab), Nice, France.
• 1990-92 Research Fellow CR2 CNRS, Centre de Biochimie, CNRS (J Pouyssegur's lab), Nice, France
• 1992-95 WHO and NIH Fogarty Fellow, Whitehead Institute/ MIT (RA Weinberg's lab), Cambridge, USA.
• 1996-98 Team leader ATIPE CNRS & CR1 CNRS, Institut de G.n.tique Mol.culaire (IGMM), Montpellier
• 1999-14 Team leader & DR CNRS, Institut de G.n.tique Mol.culaire (IGMM), Montpellier
• Since 2015 - Co-Team Leader with Dr. C Theillet of an INSERM team at IRCM U1194, Montpellier
• 2015-2020 - Director of the Institute IRCM INSERM U1194, ICM, University of Montpellier

• 2021-2026- renewal of my mandate of Director of IRCM U1194 (Vague A HCERES), but I will quit this position in july 2022 / planed turnover.  

SCIENTIFIC EXPERTISE, ADMINISTRATION AND SCIENTIFIC RESPONSIBILITIES
Main, ongoing:

• Director of IRCM U1194
• Member (Mb) of the Scientific Council of the “Fondation ARC”
• Mb of the Expert Committee of the AVIESAN / Cancer
• Mb of the Scientific Council of Curie Institute (Research dept, Paris)
• Mb of the Scientific Council of the Montpellier Cancer SIRIC, and of the FHU EVOCAN Montpellier
• Mb of the Scientific Council of the Canceropole GSO (Grand Sud-Ouest)
• Mb of the board of the LabEx EpigenMed /MUSE I site Montpellier University, Montpellier
• Mb of the Scientific council of the Bio-health department of Montpellier University
• Co-coordinator of the Cancer Axis of the "P.le Rabelais", Montpellier University
• Mb of coordination committees COCOR and CORT (translational Res.) of the Cancer Hospital ICM.

Selection of other ongoing duties and former duties related to Academic research:
• Mb of Scientific Council of the "Fondation pour la Recherche M.dicale (FRM)" (2014-18), Paris.
• Mb of the scientific panel CN2 of ARC foundation (2001-05 and from 2009-14), Villejuif.
• Mb of the national CSS-5 of INSERM (2003-07), Paris.
• Mb of the national CSS-3 of INSERM (2012-16), Paris.
• Mb of the CDD-Inserm 3-5 years program (2005-08), Paris.
• Mb of the Avenir/Atipe INSERM/CNRS program LS4 (2009), Paris.
• Mb of the scientific committee of the Ligue Contre le Cancer of Paris (08-09).
• Mb and Chaiman of the “Fondation de France (FDF)” / Cancer committee (Mb 2008-12, Chairman 2010-2012).
• Mb of the Institut Curie “seniorisation” committee (2017). Paris
• Mb of the Inserm “Ad hoc” Inserm Committee (2018). Paris
• Mb of 8 (5 as chaiman) Aeres/Hcres review committees.
• Chaiman or Mb of Scientific Advisory Boards (CDR Inserm Hopital St Antoine Paris (2007-11), IARC WHO Lyon (2004), Onco. Dept CRCNA Nantes (2015), GIGA Li.ge Belgium (2014, 2018, 21), UMR 7216 Paris Diderot (2016), IECB Bordeaux (2018-2022).
• Mb of the Board of trustees (CA) of the Canceropole GSO (2015-16)
• Mb of the GDRI France-Japan / cancer research (2011-2014)
• Mb of the group of experts in charge of pre-writing the National Plan Cancer3 (French Research Ministry 2013), Paris
• Mb of the elected Board of trustees (CA) of the Languedoc Roussillon COMUE
• Mb of the DVS (2013-15), "innovation th.rapeutique en canc.rologie", Paris
• Mb of juries of scientific prizes (Oberling since 2012, “Grand prix” FDF (2010-2012), ARC (2002, 04, 09, 2019), Ruban Rose/Estee Lauder (“Très grand Prix” 2017, 18), Hauser P (2001), Prix Rosen and Tartois of FRM (2014-18) etc..

TEACHING
Ad-hoc / occasional participation since 2000 in academic teaching at the master or PhD levels in various universities (Montpellier, Nice, Utrecht, Helsinki, Lyon, Bordeaux, Paris, Toulouse…).   PhD adviser (11 since 96).  Mb or chairman of PhD or HDR Juries (47 since 1996).  Mb of juries of selection of University professors and co-Chaiman of PhD recruitment jury (Montpellier, Toulouse 3 University Copenhagen University, Lyon University). “Formation permanente” SANOFI 1998-2001)etc…

PRIZES, HONOURS AND AWARDS
• International NIH Fogarty Fellow (major, 1993-95).
• WHO-IARC international Fellow (1992-93), ATIPE CNRS (1996-98).
• Team Labelled by the Fondation pour la Recherche Medicale (FRM 2007-09)
• Team Labelled by the French Ligue Contre le Cancer (2011-14)
• "Delahautemaison" Prize of the FRM (2007)
• "Turpin" Grand Prize / Institut de France - French Académie des Sciences (2008),
• Prime d'excellence CNRS (2009-13)
• " Raymond Rosen" Prize of the FRM (2013).

SCIENTIFIC PRODUCTION
Total: 88 original publications + 19 reviews/ Book chapters + 1 Patent.
Total citations: 9600 (Web of Sciences, 2020). H index 42.
Selection of representative publications as first/co-first or last /co-last senior author
Sardet C et al (1989) Cell 56, 271 - Sardet C et al (1990) Science 247:723 -  Sardet et al (1990) J Biol Chem 29: 19166 -Sardet C et al (1995) PNAS USA 92: 2403 – Lenormand, Sardet et al (1993) J Cell Biol 112: 1079 Le Cam et al (1999) EMBO J 18:1878 - Fabbrizio et al (1999) Oncogene 18(30:4357 Fajas L et al (2000) PNAS USA 97(14):7738 El Messaoudi et al (2006) PNAS USA 103:13351- Polanowska et al (2001) GCC 28:126 - Polanowska et al (2001) Oncogene 20:4115 - Fabbrizio et al (2002) EMBO Rep. 3(7):641 -  Li S * et al (2004 multicentric study) Science 303(5657):540 -  Paul et al (2006) Oncogene 25(40):5475 -  El Messaoudi et al. (2006) PNAS 103 :13351 -  Le Cam et al. (2006) Cell, 27:775 - Tardat et al. (2007) J Cell Biol, 179(7):1413 -  Lacroix et al. (2008) EMBO Rep 9(5):452 - Tardat et al. Nat Cell Biol 12(11):1086 - Lacroix et al. (2010) PNAS 107(49):21076 - Hatchi et al. (2011) J. Exp. Med. 208(7):1403 - Paul et al. (2012) Cell Death & Diff 19(5):900 - Rodier et al. Cell Rep 11(2):220 - Lacroix, Rodier et al. (2016) PNAS 113(39):10998 - Arnould et al. (2017) Oncotarget. 8(56):95206 - Paul et al. (2019) FEBS OB 9(1):159

Scientific summary

My scientific career has been marked by several changes of theme.

Education: studies of Chemical-Biochemical Engineering at INSA Lyon (France) and additional training in pharmacology (DEA/Master, Nice), animal biology (CNRS Strasbourg) and physiology (Woods Hole Marine Station, US)

Pre-scientific career (Strasbourg and Antarctica) 1983-1986: Biologist of the 34th French expedition to Antarctica (PE Victor mission), during which I spent 16 months on the antarctic continent to study the winter metabolic rewiring of Emperor Penguins, under the scientific direction of Dr. Y. Le Maho (CNRS, Strasbourg). Followed by a break to achieve a travel around the world on my own.

 PhD and first postdoc in Nice (France) 1986-1992: Back to France, I completed a PhD under the direction of J. Pouysségur (CNRS, Nice). I cloned the first Na+/H+ membrane exchanger (NHE1) by a functional reverse genetic approach and contributed in the discovery and characterization of other members of the new NHE family and to the demonstration of their regulation by mitogens. These exchangers (NHE1-9) are essential for the regulation of intracellular pH in all eukaryotic cells and are today recognized to be instrumental in various normal and pathophysiological situations, including cancer. In the same laboratory, I then largely contributed to one of the first demonstrations that the cellular localization of MAP kinases (ERK1/2) varied in response to mitogens and that their nuclear re-localization was a key event of cell proliferation. At the end of this first period of my career, I obtained a  permanent position from the CNRS.  

Research fellow NIH and WHO at the whitehead Institute 1992-1995:  In 1992 I joined the laboratory of Pr. RA Weinberg (Whithead Institute, MIT, Boston) where I contributed to the technical development of the first two-hybrid systems in yeast that I  used to identify and clone three novel key players in proliferation control: E2F4, E2F5 and hSNF5 /INI1. I demonstrated these new members of the E2Fs family were involved in transcriptional repression thru their association with p107 and p130 proteins (2 members of the pRB tumor suppressor family). In my own laboratory in Montpellier, I later observed that the E2F5 gene was amplified and over-expressed in breast tumors. It should also be noted that the identification and cloning of the human form of the SNF5 protein (hSNF5 / ini1) was instrumental for the demonstration by other labs, few years later, of the key role played by hSNF5 in cancer. The development of two-hybrid systems and associated cDNA libraries carried out during this postdoc were also at the origin, a few years later, of the participation of my own laboratory to the first publication of a large-scale protein-protein interactome (multicenter study/effort, led by M Vidal, DFCI, Boston). Finally, in the laboratory of Pr. RA Weinberg, I also contributed to the first characterization of the promoter of the cyclin E1 gene and its control by the E2F/pRB pathway, an essential event of the mitotic cycle.

CNRS Team leader at the IGMM (CNRS, Montpellier) 1996-2014. In 1996, I founded my own team at the IGMM of Montpellier (CNRS) supported by a starting grant from the ATIPE-Avenir program.  Our first work was focused on the p16-> cyclins/cdks -> pRB -> E2F regulatory cascade and their target genes, highlighting novel E2F-containing repressor complexes and the role played by chromatin in the periodic expression of cyclins. In particular, we demonstrated that type II arginine-methyltransferases (PRMTs II / PRMT5) play a role in the transcriptional and chromatin regulation of mammalian genes, including cyclin E1. We also proved that another arginine methyl-transferase (type I PRMT, CARM1) was involved in the control of this gene and, in breast cancers, this was in part responsible of cyclin E1 over-expression, suggesting for the first time that PRMTs could play a role in the oncogenic process. Our team also provided the first demonstration of the role of the histone Lysine-methyltransferase PR-Set7/set8 in the control of DNA replication.  In parallel we "re-discovered" and characterized the biological functions of the transcription factor E4F1, an essential but poorly studied player in the control of the balance between metabolism, proliferation and survival. E4F1 was initially identified biochemically in the 1980s as a transcriptional activity activated by the adenoviral oncoprotein E1A and essential for the replication of transforming adenoviruses (type V). However, unlike other adenoviral oncoprotein targets discovered at the same time (i.e.pRB/E2F, p300, p53 etc.), E4F1 remained inexplicably "anonymous". Our work, and later those of my brilliant former student and colleague Laurent Le Cam at the IRCM, have now positioned E4F1 as a key regulator of proliferation/survival, just as important as the other "illustrious" targets of viral oncoproteins. We showed that E4F1 is at the crossroads of different signaling pathways involved in oncogenesis and metabolism, thru the direct transcriptional regulation of a hundred or so genes, but also thru the formation of protein complexes with tumor suppressors (pRB, p53, p14ARF, DRAL/FHL2 and RassF1). In particular, we showed that E4F1 is an atypical transcription factor that also acts as an atypical E3 ubiquitin ligase on p53, an activity important for directing the p53 response towards the activation of a cycle arrest program rather than a pro-apoptotic program. This discovery placed E4F1 at the center of the "decision" process between cell death and proliferation. The development of E4F1 deficient mice (constitutive or inducible KO in different tissues and in different genetic backgrounds, collaboration with the team of L Le Cam) showed this factor is essential for early embryonic development and for the survival of epithelial stem cells and of most cancer cells deficient for the p53 pathway. We also explored the p53-independent role of E4F1, in particular in non-proliferative tissues, and showed that it directly controls the expression of limited set of genes, half of which being involved either in mitochondrial function and metabolism or in the response to stress and DNA damage (including Chek1). In particular, these studies revealed that E4F1 directly controls a hitherto unknown "Metabolic Regulon" (composed of 5 genes) essential for the Pyruvate Deshydrogenase (PDC Complex) activity and for the energy and metabolic homeostasis of normal and cancer cells.

Inserm team leader and director of the Montpellier Cancer Research Institute (IRCM U1194), 2015-2022. In 2013, I was contacted by the Cancer Research Institute of Montpellier to take the lead of their AERES project for the renewal/re-creation of the unit for the 2015-2020 contract. In January 2015, after two long years of evaluation and recruitment/re-organization (additional building and teams), I joined the IRCM and officially became the new director of this research center under the supervision of Inserm, the University of Montpellier, and the Montpellier Cancer Hospital (CLCC-ICM). IRCM (5000m2 building) is located on the campus of the cancer hospital and currently brings together more than 220 people organized in 15 Inserm teams, 2 junior teams, support services and technical platforms. The activity of managing such rapidly expanding Institute at the research-clinical interface is a very exciting but very time consuming "adventure" for a scientist. Therefore, in 2015 I decided to reduce the size of my former research group and to merge it with a team of the IRCM led by Dr. Charles Theillet, recognized for its work in the field of molecular genetics of breast and ovarian cancers. This was accompanied, gradually, by a reduction in the number of my previous research projects and a refocusing on the links between cell metabolism, cell cycle checkpoints and the response to replicative stress in breast and ovarian cancers, based on model systems developed at IRCM (includingwell-characterized PDTX models). Our new team entitled "Genetic and Phenotypic Plasticity of Cancers (GPPC)", develops several projects ranging from the dysregulation of amino acids (Proline) and nucleotides (Pyrimidine, DHODH) metabolism in tumor cells to translational questions aiming at exploring the phenotype of residual tumor cells or at broadening the therapeutic offer in triple negative and high grade ovarian cancers (synthetic lethality, drug combinations targeting DHODH, Cdks, PARP, Chek/ATR, and HR… ).

In 2019-2020, I coordinated again the project of re-creation / re-organization of the IRCM for the 2021-2026 contract (HCERES, Vague A) that resulted, in January 2021, in the official re-creation of the Institute under my directorship. Convinced that the IRCM is now on the right track, and tired of the past 8 full-time years to manage the daily life, the COVID crisis and the waves of evaluation and expansion of the IRCM, I sincerely wish, for the few years remaining before my retirement, to refocus on my scientific activity (which is losing momentum) and on various external steering committees serving the scientific community. Therefore, in consultation with IRCM staff, I have recently engaged a procedure to pass the reins of the institute to a new board of direction in july 2022.