Judith FAVIER, PhD

Team 13-Genetics and Metabolism of Rare Cancers

My PhD research focused on the study of the hypoxia-inducible factor (EPAS1 or HIF2a) in angiogenesis, during development using the chicken embryo and in human tumor tissues. After a postdoctoral stay in Montreal, where I deepened my technical skills in the study of angiogenesis and tumorigenesis, using both in vitro and in vivo mouse models, I came back to France to join, as a post-doc, the team of X. Jeunemaitre in the Collège de France where I was recruited as Inserm research associate (CR2) in 2007 to launch a research program on Pheochromocytomas and Paragangliomas (PPGL). I created with Anne-Paule Gimenez-Roqueplo, Oncogeneticist at HEGP, the PPGL group, that we moved to the PARCC in 2009.  I received a Young Investigator Chair of excellence Award (ANR) in 2012, and was strongly implicated in European collaborative projects (ENS@T-Cancer, granted by FP7-HEALTH in 2011), which allowed me to conduct an innovative research on the molecular processes that regulate the tumorigenesis of PPGL, with a more pronounced interest in the malignant forms linked to SDHB gene mutations. In 2014, I was promoted Inserm Research Professor (DR2) and became co-PI of an Inserm team dedicated to the study of PPGL. I was promoted Inserm Research Professor (DR1) in 2022.

My research strategy, based on strong and long lasting collaborations, aims to investigate the genetics and biology of PPGL using cutting-edge technologies and benefits from a unique access to patients and biosamples. This approach has been highly successful and our team is recognized as the top international level in the field. In 2015, I was elected as co-chair of the International Pheochromocytoma and paraganglioma research Support Organization (PRESSOR) and Head of the PPGL working group of ENS@T in 2021. In 2019, I started a 5-year term as the full PI of the Inserm Team “Genetics and Metabolism of Rare Cancers. My research strategy has always embraced multidisciplinary approaches and combined strength from the clinics and basic sciences, which I believe are crucial to address important medical and scientific questions about angiogenesis, oncogenesis and cancer metabolism.

.

Current position———————————————————————————————————————————————————–

• 2019: Team Leader, Inserm team “Genetics and Metabolism of Rare Cancers”
• 2022: Research Director (DR1 Inserm) – PARCC-HEGP

.

Previous positions———————————————————————————————————————————————————–

• 2014: Research Director (DR2 Inserm) – PARCC-HEGP
• 2014-2018: co-Team Leader– PARCC-HEGP
• 2011-2014: Senior Researcher (CR1 Inserm) – PARCC-HEGP
• 2009: Group leader of the “PPGL” laboratory – PARCC-HEGP, Paris
• 2007-2011: Junior Researcher (CR2 Inserm) – Collège de France and PARCC-HEGP
• 2005-2007: Post-doc – Collège de France, Inserm U772
• 2003-2005: Post-doc – Montreal Heart Institute, Canada

.

Education———————————————————————————————————————————————————–

2013          Diploma in accreditation to supervise PhD students (HDR). Université Paris Descartes

2011           Graduation in «Animal experimentation, Ethics and welfare” level 1 (for project leaders)

2002          PhD in Genetics (Director: JM Gasc) summa cum laude, University Paris Descartes, France.

.

Editorial functions and  scientific committees———————————————————————————————————————————————————–

• 2021-now: Chair of the PPGL working group of the European Network for the Study of Adrenal Tumors, member of the ExCo, Tresurer of ENSAT
• since 2022: member Management Committee of the COST CA20122 – Harmonizing clinical care and research on adrenal tumours in European countries
• 2018-now: Associate Editor at Endocrine-related Cancer
  
• 2018-now: Elected member of the PPGL working group of the European Network for the Study of Adrenal Tumors
• 2017-2019: Member of the Scientific Board of the French Society of Endocrinology (SFE)
• 2016-2021: Member of INSERM commission CSS2
• 2015-now: Co-chair of the international Pheochromocytoma Research Support Organization (PRESSOR).
• 2015-now: Fouding member of the “Rare Cancers” working group from the Cancéropôle Ile de France
• 2010-now: Member of the European Network for the Study of Adrenal Tumors (ENS@T)
• 2009-now: Co-Chairman of the «Animals models» working group from PRESSOR.

.

Funding———————————————————————————————————————————————————–

• 2022-2026     The Paradifference Foundation
• 2022               CARPEM
• 2021-2024     INCA (PRTK 2020) : “COMETE-CARE : positioning of molecular markers in clinical routine for the management of patients with adrenal cancers”
• 2020-2023    INCA-PLBIO- “MIRENVI”
• 2020-2023    ANSES – SOHO-EpiMetCan
• 2020-2023    Plan ECO-PHYTO II -SOHO- SDHi ecOHealth 
• 2019-2020    CARPEM : Appel d’offre Projets émergents
• 2018-2019    Foncer contre le cancer- “Circulating DNA in metastatic renal cell carcinomas”
  
• 2018-2019   CARPEM : Appel d’offre Projets émergents
  
• 2017-2020   The Paradifference Foundation
• 2017-2022   Equipe labéllisée de la Ligue contre le Cancer
• 2016-2018   The Paradifference Foundation – Metabolic escape of SDHB defective tumours
  
• 2015-2016    Cancéropôle Ile-de-France –  Emergence 2015 –« 3D-INVITROPP »
• 2015-2020    Horizon 2020 – H2020-PHC-2014- « ENS@T-HT»                   
  
• 2014              CARPEM : Appel d’offre Projets émergents
• 2015-2020    Programme for Translational Cancer Research – INCA – “COMETE-TACTIC”
• 2014-2016    Plan Cancer : Appel à projets Epigénetique et Cancer 2013- «METABEPIC  »
•  2012-2015    ANR jeunes chercheurs – «MODEOMAPP”. 
  
• 2011-2015     FP 7 COOPERATION – HEALTH-2010-2.4.1-5 – « ENS@T-Cancer»
• 2010               Groupe des Tumeurs Endocrines (GTE)- “Sdhb KO mice”
• 2009-2012    ANR 08 GENOPATH –« MITOXY»
  
• 2005-2007    Grant from the ARC Fondation 

.

Awards———————————————————————————————————————————————————-

• 2002: Young Researchers award (Fondation Bettencourt-Schueller)
• 2013-2016: Prize of Scientific Excellence (PEDR Inserm)
• 2017-2020: Prize of Scientific Excellence (PEDR Inserm)
• 2021-2024: Prize of Scientific Excellence (PEDR Inserm)

   .

Main international conferences as an invited speaker (past 10 years)————————————————————————————————————————————-

•  2022 : 5th meeting of the Paradifference Foundation (Suède)
• 2022 : Congress of the Polish Society of Endocrine Oncology. Genetic diversity of pheochromocytoma / paraganglioma and prospects for targeted therapies – summary of the experience.
• 2021 : EMBO Workshop on Metabolism, the Immune System and Cancer (Spain) – Succinate dehydrogenase in cancer 
• 2021 : 4th meeting of the Paradifference Foundation 
• 2021 : Metabolism and Cancer symposium (Bordeaux)
• 2021 : WorldMEN Meeting (World Multiple Endocrine Neoplasia, Marseille) – “Targeted therapies: lessons from in vitro studies”
• 2020 : 3rd meeting of the Paradifference Foundation – “Selecting the specific features and oncogenic mechanisms of SDHB metastatic PPGL”
• 2019 : Journées Internationales d’Endocrinologie Clinique – Henri-Pierre KLOTZ (Paris)- « Precinical Models and in vivo imaging of SDHB-deficient paragangliomas”
• 2019 : Advances at the interface between metabolism and epigenetics (Cambridge, UK)-  “Uncoupled effects of TET inhibition and hypoxia in SDH-deficient cells “
• 2018 : EACR Conference Series- Mechanisms to Therapies – Innovation in Cancer metabolism (Bilbao)- “Epigenetic reprogramming of SDH-deficient PPGL”
• 2018 : 20th European Congress of Endocrinology – ECE 2018 (Barcelona) – “Epigenetic and metabolic reprogramming of SDH-deficient PPGL”
•  2018 : 2nd meeting of the Paradifference Foundation, (Goteburg)- “Epigenetic and metabolic reprogramming of SDH-deficient PPGL”
• 2017 : 5^th International Symposium on Pheochromocytoma (Sydney)-  « Cluster I paragangliomas –spanners in the TCA cycle ».
• 2016 : “Metabolism and Cancer “ symposium (Palavas les Flots)- “Mitochondrial deficiencies in the predisposition to paragangliomas”
• 2016 : The Molecular Stratagem of Glioblastoma, Neuroscience School of Advance Sciences (Cortona, Italie) –« Oncometabolites »
• 2016 : Tour d’Europe de l’AP-HP : Uro-oncologie (Paris) «Resistance to antiangiogenic therapies”
• 2015 : abcam meeting on Cancer and Metabolism (Cambridge) «Deciphering the oncometabolic functions of succinate in paraganglioma»
• 2015 : ENDO 2015 (Endocrine Society)(San Diego)   «SDH and Hypermethylation in Pheochromocytoma»
• 2012 : MitOx Meeting (Oxford).  «The quest for an SDHB-related paraganglioma mouse model»
• 2011 : 3^nd International Symposium on Pheochromocytoma (Paris).   « The Warburg effect in pheochromocytomas and paragangliomas ».

.

Main national conferences as an invited speaker (past 10 years)————————————————————————————————————————————-

• 2022 : Congrès de la Societé Française d’Endocrinologe (Nantes)
• 2021 : Séminaire ITMO Cancer – Impacts du Programme Epigénétique et Cancers – Perspectives de la discipline- « Impact des désordres métaboliques sur les modifications épigénétiques dans le cancer »
• 2017 : Congrès de la Societé Française d’Endocrinologe (Poitiers)-   « Métabolomique et Fluxomique des Phéochromocytomes »
• 2017 : Congrès de la Societé Française d’Angiogenèse (Toulouse) – « Angiogenesis in paragangliomas »
• 2016 : 5ème colloque annuel de l’ITMO PMN (Paris) – Mutations des gènes SDH et paragangliomes : rôle des oncométabolites dans le cancer
• 2015 : 18e congrès du Groupe Français de Bioénergétique (Mittlewhir)-  «Succinate dehydrogenase in cancer»
• 2014 : Club Chromatine de Paris (Institut Pasteur, Paris) – “SDH mutations and the hypermethylator phenotype in paraganglioma”.
• 2013 : 1ère Journée Universitaire d’Endocrinologie Paris Sud, Bicêtre – «Mutations SDH et phénotype tumorale dans les paragangliomes»
• 2013 : Journées Scientifiques de l’Université de Nantes- Colloque «Métabolisme et chimiorésistance des cancers». «Gènes SDH et prédisposition au cancer»
• 2013 : Séminaires «Cartes d’Identité des Tumeurs», Ligue Nationale contre le Cancer, Paris – «Analyse génomique intégrée des phéochromocytomes et paragangliomes »
• 2012 : 6^e colloque du “Réseau MeetOchondrie” (Soustons, France) – «Rôle des gènes SDH dans la prédisposition au cancer.»

.

Current teaching activities———————————————————————————————————————————————————–

• Since 2020    Lecture on Metabolism and Cancer, DESC de Cancérologie, Université de Paris
• since 2018    Lecture on Molecular Genetics of Krebs cycle Alterations in Cancer, Master Sciences de la Vie et de la Santé, Mention européenne de Génétique, Universités Paris Descartes -Paris Diderot
• since 2018    Lecture on Metabolism and Cancer, module Thérapies ciblées en onco-hématologie, Formation de l’Ecole Doctorale HOB, Université Denis Diderot
• 2017                e-learning on Metabolism and Cancer, DES Oncologie, Collège National des Enseignants en Cancérologie.
• since 2013    Lecture on Resistance to anti-angiogenic therapies, Enseignement Pôle Cancérologie et Spécialités, Cours de Cancérologie transversal, HEGP, Paris
• since 2013    Lecture on Tumor Angiogenesis, Master BCPP, Spécialité « Vaisseaux Hémostase », Université Paris Diderot
• 2012-2018    Lecture on Genetics of pheochromocytoma Magistère Européen de Génétique, Universités Paris Diderot-Paris Descartes
• since 2011    Lecture on Pseudohypoxia and cancer, M1 santé, Université Paris Descartes
• since 2009   Lecture on Resistance to anti-angiogenic therapies,  DES d’oncologie médicale

.

Patent———————————————————————————————————————————————————–

• 2018-  Patent deposit by Inserm Transfert : «Methods for predicting metastatic potential in patients suffering from SDHB-mutated paraganglioma»- EP18306527.5.

.

Main Publications———————————————————————————————————————————————————–

1. Goncalves J, Moog S, Morin A, Gentric G, Müller S, Morrell AP, Kluckova K, Stewart TJ, Andoniadou CL, Lussey-Lepoutre C, Bénit P, Thakker A, Vettore L, Roberts J, Rodriguez R, Mechta-Grigoriou F, Gimenez-Roqueplo AP, Letouzé E, Tennant DA, Favier J. Loss of SDHB Promotes Dysregulated Iron Homeostasis, Oxidative Stress, and Sensitivity to Ascorbate. Cancer Res. 2021 Jul 1;81(13):3480-3494.
2. Morin A, Goncalves J, Moog S, Buffet, Castro-Vega LJ, Woszczyk J, Fontenille M, Gimenez-Roqueplo AP, #Letouzé E and #Favier J. TET-mediated hypermethylation primes SDH-deficient cells for HIF2a driven mesenchymal transition Cell Reports, 2020 Mar 31;30(13):4551-4566.e7.

2. Lussey-Lepoutre C, Bellucci A, Burnichon N, Amar L, Buffet A, Drossart T, Fontaine S, Clément O, Benit P, Rustin P, Groussin L, Meatchi T, Gimenez-Roqueplo AP, Tavitian B and Favier J. Succinate detection by in vivo ¹H-MR spectroscopy identifies germline and somatic SDHx mutations in paragangliomas. Eur J Nucl Med Mol Imaging 2020 Jun;47(6):1510-1517
3. Kluckova K, Thakker A, Hindshaw RL, Tearle JLE, Goncalves J, Lavery GG, Favier J and Tennant DA. Succinate dehydrogenase-deficiency in a chromaffin cell model retains metabolic fitness through the maintenance of mitochondrial NADH oxidoreductase function. FASEB J 34:303–315

4. Favier J, Meatchi, T, Robidel E, Badoual C, Sibony M, Ngyen AT, Gimenez-Roqueplo AP and Burnichon N. CAIX immunohistochemistry as a tool to predict germline and somatic VHL mutations in pheochromocytoma and paraganglioma – A retrospective and prospective study. Modern Pathol ; 2020 Jan;33(1):57-64.
   

5. *Job S, *Draskovic I, *Burnichon B, Buffet A, Padilla-Girola M, Venisse A, Robidel E, Cros J, Badoual C, Verkarre V, Sibony M, Amar L, de Reyniès A, Bertherat J, Arturo Londoño-Vallejo A, #Favier J, #Castro-Vega LJ and #Gimenez-Roqueplo AP. Telomerase Activation and ATRX Mutations Are Independent Risk Factors for Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res, 2019 ;25(2):760-770. « Highly Cited Paper »

6. Buffet A, Morin A, Castro-Vega LJ, Habarou F, Lussey-Lepoutre C, Letouzé E, Lefebvre H, Guilhem I, Raingeard I, Tran T, Tchara L, Bertherat J, Amar L, Ottolenghi C, Burnichon N, #Gimenez-Roqueplo AP and #Favier J. Germline mutations in the mitochondrial 2-oxoglutarate/malate carrier SLC25A11 gene confer a predisposition to metastatic paragangliomas. Cancer Res 2018; 78(8):1914-1922 « Highly Cited Paper »
7. Castro-Vega LJ, Kiand RS, Buffet A, Burnichon N, Khalifa E, Simian C, Galan P, Amar a, Bouatia-Naji N, #Favier J, #Bressac-de Paillerets B, #Gimenez-Roqueplo AP. The MITF, p.E318K variant as a risk factor for pheochromocytomas and paragangliomas. J Clin Endocrinol Metab. 2016 ; 101(12):4764-4768

8. *Lussey-Lepoutre C, *Bellucci A, Morin A, Buffet A, Amar L, Janin M, Martinelli C, Ottolenghi C, Zinzindohoué F, Autret G, Burnichon N, Robidel E, Banting B, Fontaine S, Cuenod CA, Benit P, Rustin P, Halimi P, Fournier L, Gimenez-Roqueplo AP, #Favier J and #Tavitian B. In vivo detection of succinate by magnetic resonnace spectroscopy as a hallmark of SDHx mutations in paraganglioma. Clin Cancer Res. 2016;22(5):1120-9
9. *Lussey-Lepoutre C, *Hollinshead KER, Ludwig C, Menara M, Morin A, Castro-Vega LJ, Parker SJ, Janin M, Martinelli C, Ottolenghi C, Metallo C, Gimenez-Roqueplo AP, #Favier J and #Tennant DA. Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism. Nat Commun. 2016;6:8784.

10. Castro-Vega L-J, Lepoutre-Lussey C, Gimenez-Roqueplo A-P and Favier J. Rethinking pheochromocytomas and paragangliomas from a genomic perspective. Oncogene 2016 Mar 3;35(9):1080-9. (IF 6.8) Invited Review
11. Favier J, Amar L, Gimenez-Roqueplo A-P. Paraganglioma and pheochromocytoma: from genetics to personalized medicine. Nature Rev Endocrinol. 2015; 11(2):101-111 (IF 20.2) Invited Review. « Highly Cited Paper
12. *Castro-Vega L-J *Letouzé E, *Burnichon N, Buffet A, Disderot P-H, Khalifa E, Loriot C, Elarouci N, Morin A, Ménara M, Lepoutre-Lussey C, Badoual C, Sibony M, Dousset B, Libé R, Zinzindohoue F, Plouin P-F, Bertherat J, Amar L, de Reyniès A, #Favier J and #Gimenez-Roqueplo A-P. Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas. Nat Commun. 2015 ; 6:6044. (IF 12.4)
13. *Letouzé E, *Martinelli C, Loriot C, Burnichon N, Abermil N, Ottolenghi C, Janin M, Menara M, Nguyen AT, Benit P, Buffet A, Marcaillou C, Bertherat J, Amar L, Rustin P, De Reyniès A, #Gimenez-Roqueplo AP and #Favier J.  SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 2013 ; 23(6):739-52 (IF 22.8). « Highly Cited Paper »
14. Favier J, Buffet A, Gimenez-Roqueplo AP. HIF2A Mutations in Paraganglioma with Polycythemia. N Engl J Med; 367(22):2161-2, 2012. (IF 79)
15. *Burnichon N, *Buffet A, Parfait B, Letouzé E, Laurendeau I, Loriot C, Pasmant E, Abermil N, Valeyrie-Allanore L, Bertherat J, Amar L, Vidaud D, #Favier J and #Gimenez-Roqueplo AP. Somatic NF1 Inactivation is a Frequent Event in Sporadic Pheochromocytoma. Hum Mol Genet. 2012; 21(26):5397-405. (IF 4.9)
16. Loriot C, Burnichon N, Gadessaud N, Vescovo, L, Amar L, Libé R, Bertherat J, Plouin PF, Jeunemaitre X, #Gimenez-Roqueplo AP and #Favier J. Epithelial to mesenchymal transition is activated in malignant pheochromocytomas and paragangliomas caused by SDHB gene mutations. J Clin Endocrinol Metab. 2012; 97(6):E954-62. (IF 5.8
17. *Castro-Vega LJ, *Buffet A, *de Cubas AA, Cascon, A, Menara M, Khalifa E, Amar L, Azriel S, Bourdeau I, Chabre O, Curras-freixe M, Franco-Vidal V, Guillaud-Bataille M, Simian C, Morin A, Leton R, Gomez-Grana A, Pollard PJ, Rustin P, #Robledo M, #Favier J, #Gimenez-Roqueplo AP. FH mutations confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet. 2014 ; 23(9):2440-6. (IF 4.9)
18. Burnichon N, Vescovo, L, Amar L, Libé R, de Reynies A, Venisse A, Jouanno E, Laurendeau I, Bertherat J, Plouin PF, Jeunemaitre X, #Favier J and #Gimenez-Roqueplo AP. Integrative Genomic Analysis Reveals Somatic Mutations in Pheochromocytoma and Paraganglioma. Hum Mol Genet 2011; 20(20):3974-85 (IF 4.9)
19. *Korpershoek E, *Favier J, *Gaal J, Burnichon N, van Gessel B, Oudijk L, Badoual C, Gadessaud N, Venisse A, Bayley JP, Oldenburg R, de Herder WW, Tissier F, Plouin PF, van Nederveen FH, #Dinjens WNM, #Gimenez-Roqueplo AP and # de Krijger RR. SDHA immunohistochemistry detects SDHA gene mutations in paragangliomas and pheochromocytomas. J Clin Endocrinol Metab 2011; 96(9):E1472-6. (IF: 5.8)
20. *van Nederveen FH, *Gaal J, *Favier J, Korpershoek E, Oldenburg RA, de Bruyn EM, Sleddens HF, Derkx P, Rivière J, Dannenberg H, Petri BJ, Komminoth P, Pacak K, Hop WC, Pollard PJ, Mannelli M, Bayley JP, Perren A, Niemann S, Verhofstad AA, de Bruïne AP, Maher ER, Tissier F, Méatchi T, Badoual C, Bertherat J, Amar L, Alataki D, Van Marck E, Ferrau F, François J, de Herder WW, Peeters MP, van Linge A, Lenders JW, Gimenez-Roqueplo AP, de Krijger RR, Dinjens WN. An easy and low-cost routine immunohistochemical procedure for the detection of Paraganglioma and Pheochromocytoma patients with germline SDHB, C or D gene mutations. Lancet Oncol 2009 10(8): 764-71.  (IF 36) « Highly Cited Paper »
21. Favier J, Plouin PF, Corvol P and Gasc JM. Angiogenesis and vascular status in pheochromocytomas: distinctive traits in malignant tumors. Am J Pathol 2002 ; 161(4) : 1235-46. (IF 4.1)