Jean-François PEYRON :
Date of birth : september 24th, 1961, Nice, France. married, 2 children.
current position :
- Head of Team #4 : Inflammation, Cancer, Cancer Stem Cells.
INSERM U895 Centre Méditerranéen de Médecine Moléculaire (C3M),
director : Yannick Le Marchand-Brustel.
- Interface contract with CHU Nice (Pediatrics Oncology and Hematology departments)
Professional experience :
- INSERM DR2 : 1998
- Habilitation à diriger des Recherches. 1998. Université de Nice.
- Postdoctoral fellow DNAX Research Institute of Molecular and Cellular Biology. Palo Alto. California. USA. 1989-1991. Human Immunology Department, Head Dr. Jan De Vries, group supervisor : Dr. Hergen Spits.
- Training period in Dr. Cox Terhorst’s lab. July 1990. Dana Farber Cancer Institute. Harvard Medical School. (Boston. Massachussets, USA).
- INSERM CR2 : 1988.
- ARC fellowship : 1987.
- Doctorat d'Université en Sciences de la Vie (PhD). 1987. Université de Nice.
- DEA Pharmacologie de l'Université de Nice. 1984.
- Maîtrise de Biochimie. 1983. Université de Nice.
- Licence de Biochimie. 1982. Université de Nice.
- Baccalauréat série C. 1979. Rectorat de Nice.
Expertise/consulting, grant evaluation :
Ligue contre le cancer, comité Haute Savoie (2007), Cancéropôle Ile de France (2008), Cancer Research UK (2008), INCa (2008), GEFLUC Flandres (2010).
Referee for AERES (2009).
Referee for the Comité d’Evaluation du CHU Nice postes d’accueil CHU-CNRS (2008-2009).
Tutor for new CR INSERM (CSS2) : M Fatah Ouaz (2007) et M Nicolas Bidère (2008).
Reviewer for :
Blood, Cancer Research, Embo J, Oncogene, Mol Cell Biol, J Mol Endo, J Cell Science, J Cell Biol, BBA, BBRC, Febs Letter, Mol Pharmaco, Biochem Pharmaco, Cancer Letters, Eur J Cell Biol, Leuk Research, Med/Sci, Exp Cell Res, Radiation & Environmental Biophysics.
Master Nice University, Ecole Polytechnique Universitaire, Sophia Antipolis (occasionally).
Member of >25 PhD thesis jurys since 1998 (rapporteur, examinateur, Président). 1 jury in Belgium.
Invited conference :
International meeting of the International Cell Death Society “Cell death and cancer“.
“NF-kB at the cross roads of survival or death in cancer cells“. Nice, 2007.
Scientific councils appartenance :
- Elected member to the council of Ecole Doctorale 85, Université de Nice (2010-)
- Elected member to the Scientific council of the Faculty of Medicine, Nice (2010-)
- Coordination committee C3M/U895 (2008-)
- Co-supervisor “Cell deaths“ theme, Cancéropôle PACA (2008-)
- IFR50 council (2005-)
Scientific honors :
- Prix Joseph Amalric, Ligue contre le cancer, comité du Var, 1997.
Scientific production :
59 articles, 2449 citations, h index = 28
NF-kB in cancer : The team demonstrated in vitro the benefits of targeting the NF-kB transcription factor (pharmacological IKK2 inhibitor, AS602868) to trigger apoptosis of primary cancer cells displaying an abnormal constitutive activation of the pathway (Acute Myeloid Leukemia, Chronic Myeloid Leukemia). Inhibition of NF-kB interferes with engraftment of AML cells into NOD-SCID mice suggesting that NF-kB could support the survival of leukemic stem cells. Targeting NF-kB, downstream of the Bcr-Abl oncogene, bypasses the resistance of CML cells to imatinib, even of those bearing the T315I mutation that confers resistance to all currently available Bcr-Abl inhibitors. Moreover, inhibition of NF-kB could potentiate the apoptotic action of classical chemotherapeutic drugs in various models (AML, colon cancer cell line).
We demonstrated the existence of an apoptosis amplifying loop when caspases impaired NF-kB anti-apoptotic actions through cleavage/inactivation of NEMO, the scaffold component of the IKK complex that is crucial for NF-kB activation.
Role of NF-kB in a murine T cell lymphoma model :
Pathologic activation of the PI3K/Akt pathway upstream of NF-kB is a common feature of T-cell malignancies. We are using a murine T cell lymphoma model after specific inactivation (cre-lox) of the PTEN tumor suppressor gene in T cells (tPTEN-/-).
To genetically dissect the action of NF-kB in the generation of tPTEN-/- lymphomas and identify its transformation-relevant target genes, we use several conditional double KO mice in order to either block (IKK2f/f, p65-RelAf/f) or stimulate (IkB-a f/f) NF-kB activation in a tPTEN-/- background.
Affymetrix gene profiling of tPTEN-/- tumors highlighted a marked perturbed metabolic signature that is explored in silico (GSEA/CMAP/IPA) to discover new potential targets. Metastasis relevant genes will be extracted from analysis of invasive/non-invasive tumors. The murine signatures will be matched to those of human lymphomas for identification of conserved genes, likely crucial for lymphomagenesis.
Cancer stem cells (CSC) and self-renewal :
CSC generates tumors, self-renew and escape therapies to induce relapse.
tPTEN-/- CSC can generate leukemia in serially transplanted nude mice. Transplantation/dilution experiments, coupled to flow cytometry will define their frequency and surface immunophenotype. The double KO mouse will help determine the importance of NF-kB for tPTEN-/- CSC self-renewal.
Besides, we have set up an inducible RNA interference model in the human K562 cell line to explore the role of the Bmi-1 transcriptional repressor that is crucial for normal and cancerous self-renewal.
NF-kB and inflammation : Using mouse models of Inflammatory Bowel Disease, we showed that NF-kB is targeted by the yeast probiotic Saccharomyces boulardii (Sb) to attenuate inflammation, by preventing expression of IL1, TNF, IL8. Sb exerts in vitro and in vivo, a protective effect during Salmonella infection by interfering with the inflammatory response through NF-kB inhibition.