Pierre VAL
Chef d'équipe
VAL
Pierre
Chef d'équipe
DR
Resume
2016 Group Leader MOP@ET team
2016 Research Director CNRS
2007 Research Associate CNRS
2003-2007 Post-doctoral Researcher, Institute of Cancer Research, London UK
1999-2003 PhD Student, Blaise Pascal University Clermont-Ferrand
Research
I am interested in the molecular mechanisms involved in the control of adrenal gland homeostasis and how their deregulation contributes to the development of pathologies. My group has demonstrated the key role of an equilibrium between WNT/b-catenin and PKA signalling pathways and of the histone methyltransferase EZH2, in establishing and maintaining the zonal differentiation pattern of the adrenal cortex. We have also shown involvement of these pathways in adrenal pathophysiology, including insufficiency (LGR4 mutations), formation of hormonally active adenomas (b-catenin and PKA), and development of aggressive cancers (alterations of b-catenin, ZNRF3 and TP53 and overexpression of EZH2). I currently investigate the role of the immune microenvironment and in particular macrophages, in the control of endocrine differentiation and cortical cell renewal, as well as in tumour initiation and progression. In this context, we have recently shown that macrophages play a central role in preventing adrenocortical carcinoma progression and in the sexual dimorphism of this cancer.
Publications
Letter to the Editor From Janot et al: « Single-Exon Deletions of ZNRF3 Exon 2 Cause Congenital Adrenal Hypoplasia ».
Published on 13 Aug 2024 in The Journal of clinical endocrinology and metabolism , vol. 109 - pp e1808-e1809
Janot C, Bachelot A, Mallet D, Simon D, Val P , Roucher-Boulez F
Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice.
Published on 21 Dec 2022 in Nature communications , vol. 13 - pp 7858
Dufour D , Dumontet T , Sahut-Barnola I, Carusi A, Onzon M , Pussard E, Wilmouth JJ , Olabe J , Lucas C , Levasseur A , Damon-Soubeyrand C , Pointud JC , Roucher-Boulez F , Tauveron I , Bossis G, Yeh ET, Breault DT, Val P , Lefrançois-Martinez AM, Martinez A
β-Catenin activation and illicit receptor expression in adrenocortical cells.
Published on 07 Feb 2022 in Endocrine-related cancer , vol. 29 - pp 151-162
Le Mestre J, Thomas M, Duparc C, Val P , Bures C, Tuech JJ, Sabourin JC, Baert-Desurmont S, Lefebvre H, Louiset E
Steroidogenic Factor-1 Lineage Origin of Skin Lesions in Carney Complex Syndrome.
Published on 12 Nov 2022 in The Journal of investigative dermatology , vol. 142 - pp 2949-2957.e9
Sahut-Barnola I , Lefrançois-Martinez AM , Dufour D , Botto JM, Kamilaris C, Faucz FR, Stratakis CA, Val P , Martinez A
Sexually dimorphic activation of innate antitumor immunity prevents adrenocortical carcinoma development.
Published on 14 Oct 2022 in Science advances , vol. 8 - pp eadd0422
Wilmouth JJ Jr , Olabe J , Garcia-Garcia D , Lucas C , Guiton R , Roucher-Boulez F , Dufour D , Damon-Soubeyrand C , Sahut-Barnola I , Pointud JC , Renaud Y , Levasseur A , Tauveron I , Lefrançois-Martinez AM , Martinez A , Val P
Loss of LGR4/GPR48 causes severe neonatal salt-wasting due to disrupted WNT signaling altering adrenal zonation.
Published on 20 Dec 2022 in The Journal of clinical investigation
Lucas C , Sauter KS, Steigert M, Mallet D, Wilmouth J Jr , Olabe J , Plotton I, Morel Y, Aeberli D, Wagner F, Clevers H, Pandey AV, Val P , Roucher-Boulez F , Fluck CE
Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.
Published on 01 Dec 2021 in The Journal of clinical investigation , vol. 131
Djari C , Sahut-Barnola I , Septier A , Plotton I, Montanier N , Dufour D , Levasseur A , Wilmouth J Jr , Pointud JC , Faucz FR, Kamilaris C, Lopez AG, Guillou F, Swain A, Vainio SJ, Tauveron I , Val P , Lefebvre H, Stratakis CA, Martinez A , Lefrançois-Martinez AM
How can we minimise the use of regular oral corticosteroids in asthma?
Published on 31 Mar 2020 in European respiratory review : an official journal of the European Respiratory Society , vol. 29
Bourdin A, Adcock I, Berger P, Bonniaud P, Chanson P, Chenivesse C, de Blic J, Deschildre A, Devillier P, Devouassoux G, Didier A, Garcia G, Magnan A, Martinat Y, Perez T, Roche N, Taillé C, Val P , Chanez P
EZH2 cooperates with E2F1 to stimulate expression of genes involved in adrenocortical carcinoma aggressiveness.
Published on 30 Aug 2019 in British journal of cancer , vol. 121 - pp 384-394
Tabbal H , Septier A , Mathieu M , Drelon C , Rodriguez S , Djari C , Batisse-Lignier M , Tauveron I , Pointud JC , Sahut-Barnola I , Ragazzon B, Assié G, Bertherat J, Lefrançois-Martinez AM , Martinez A , Val P
A ZNRF3-dependent Wnt/β-catenin signaling gradient is required for adrenal homeostasis.
Published on 01 Feb 2019 in Genes & development , vol. 33 - pp 209-220
Basham KJ, Rodriguez S , Turcu AF, Lerario AM, Logan CY, Rysztak MR, Gomez-Sanchez CE, Breault DT, Koo BK, Clevers H, Nusse R, Val P , Hammer GD
Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex.
Published on 12 Sep 2019 in FASEB journal : official publication of the Federation of American Societies for Experimental Biology , vol. 33 - pp 10218-10230
Dumontet T , Sahut-Barnola I , Dufour D , Lefrançois-Martinez AM , Berthon A , Montanier N , Ragazzon B, Djari C , Pointud JC , Roucher-Boulez F , Batisse-Lignier M , Tauveron I , Bertherat J, Val P , Martinez A
Steroidogenic differentiation and PKA signaling are programmed by histone methyltransferase EZH2 in the adrenal cortex.
Published on 26 Dec 2018 in Proceedings of the National Academy of Sciences of the United States of America , vol. 115 - pp E12265-E12274
Mathieu M , Drelon C , Rodriguez S , Tabbal H , Septier A , Damon-Soubeyrand C , Dumontet T , Berthon A , Sahut-Barnola I , Djari C , Batisse-Lignier M , Pointud JC , Richard D, Kerdivel G, Calméjane MA, Boeva V, Tauveron I , Lefrançois-Martinez AM , Martinez A , Val P
PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal.
Published on 25 Jan 2018 in JCI insight , vol. 3
Dumontet T , Sahut-Barnola I , Septier A , Montanier N , Plotton I, Roucher-Boulez F , Ducros V, Lefrançois-Martinez AM , Pointud JC , Zubair M, Morohashi KI, Breault DT, Val P , Martinez A
P53/Rb inhibition induces metastatic adrenocortical carcinomas in a preclinical transgenic model.
Published on 30 Aug 2017 in Oncogene , vol. 36 - pp 4445-4456
Batisse-Lignier M , Sahut-Barnola I , Tissier F, Dumontet T , Mathieu M , Drelon C , Pointud JC , Damon-Soubeyrand C , Marceau G , Kemeny JL, Bertherat J, Tauveron I , Val P , Martinez A , Lefrançois-Martinez AM
Mouse Models Recapitulating Human Adrenocortical Tumors: What Is Lacking?
Published on 15 Jul 2016 in Frontiers in endocrinology , vol. 7 - pp 93
Leccia F , Batisse-Lignier M , Sahut-Barnola I , Val P , Lefrançois-Martinez AM , Martinez A
Editorial: Adrenal Cortex: From Physiology to Disease.
Published on 01 Jun 2016 in Frontiers in endocrinology , vol. 7 - pp 51
Pregnancy, Primary Aldosteronism, and Somatic CTNNB1 Mutations.
Published on 14 Apr 2016 in The New England journal of medicine , vol. 374 - pp 1493-4
EZH2 is overexpressed in adrenocortical carcinoma and is associated with disease progression.
Published on 01 Jul 2016 in Human molecular genetics , vol. 25 - pp 2789-2800
Drelon C, Berthon A, Mathieu M, Ragazzon B, Kuick R, Tabbal H, Septier A, Rodriguez S, Batisse-Lignier M, Sahut-Barnola I, Dumontet T, Pointud JC, Lefrançois-Martinez AM, Baron S , Giordano TJ, Bertherat J, Martinez A, Val P
PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development.
Published on 14 Sep 2016 in Nature communications , vol. 7 - pp 12751
Drelon C , Berthon A , Sahut-Barnola I , Mathieu M , Dumontet T , Rodriguez S , Batisse-Lignier M , Tabbal H , Tauveron I , Lefrançois-Martinez AM , Pointud JC , Gomez-Sanchez CE, Vainio S, Shan J, Sacco S, Schedl A, Stratakis CA, Martinez A , Val P
Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of β-catenin in adrenocortical carcinoma.
Published on 27 Jul 2015 in Oncogenesis , vol. 4 - pp e161
Lefèvre L, Omeiri H, Drougat L, Hantel C, Giraud M, Val P , Rodriguez S , Perlemoine K, Blugeon C, Beuschlein F, de Reyniès A, Rizk-Rabin M, Bertherat J, Ragazzon B
Adrenal cortex tissue homeostasis and zonation: A WNT perspective.
Published on 15 Jun 2015 in Molecular and cellular endocrinology , vol. 408 - pp 156-64
Drelon C , Berthon A , Mathieu M , Martinez A , Val P
Aldose reductases influence prostaglandin F2α levels and adipocyte differentiation in male mouse and human species.
Published on 12 May 2015 in Endocrinology , vol. 156 - pp 1671-84
Pastel E , Pointud JC , Loubeau G , Dani C, Slim K, Martin G, Volat F, Sahut-Barnola I , Val P , Martinez A , Lefrançois-Martinez AM
WNT/β-catenin signalling is activated in aldosterone-producing adenomas and controls aldosterone production.
Published on 15 Feb 2014 in Human molecular genetics , vol. 23 - pp 889-905
Berthon A , Drelon C , Ragazzon B, Boulkroun S, Tissier F, Amar L, Samson-Couterie B, Zennaro MC, Plouin PF, Skah S, Plateroti M, Lefèbvre H, Sahut-Barnola I , Batisse-Lignier M , Assié G, Lefrançois-Martinez AM , Bertherat J, Martinez A , Val P
mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD).
Published on 15 Oct 2014 in Human molecular genetics , vol. 23 - pp 5418-28
de Joussineau C , Sahut-Barnola I , Tissier F, Dumontet T , Drelon C , Batisse-Lignier M , Tauveron I , Pointud JC , Lefrançois-Martinez AM , Stratakis CA, Bertherat J, Val P , Martinez A
Liver x receptors protect from development of prostatic intra-epithelial neoplasia in mice.
Published on 30 May 2013 in PLoS genetics , vol. 9 - pp e1003483
Pommier AJ, Dufour J , Alves G, Viennois E, De Boussac H , Trousson A , Volle DH , Caira F , Val P , Arnaud P , Lobaccaro JM , Baron S
Adrenocortical cancer and IGF2: is the game over or our experimental models limited?
Published on 12 Feb 2013 in The Journal of clinical endocrinology and metabolism , vol. 98 - pp 505-7
The cAMP pathway and the control of adrenocortical development and growth.
Published on 31 Mar 2012 in Molecular and cellular endocrinology , vol. 351 - pp 28-36
de Joussineau C , Sahut-Barnola I , Levy I, Saloustros E, Val P , Stratakis CA, Martinez A
Analysis of the role of Igf2 in adrenal tumour development in transgenic mouse models.
Published on 28 Aug 2012 in PloS one , vol. 7 - pp e44171
Drelon C , Berthon A , Ragazzon B, Tissier F, Bandiera R, Sahut-Barnola I, de Joussineau C , Batisse-Lignier M , Lefrançois-Martinez AM, Bertherat J, Martinez A , Val P
Wnt/β-catenin signalling in adrenal physiology and tumour development.
Published on 31 Mar 2012 in Molecular and cellular endocrinology , vol. 351 - pp 87-95
Berthon A , Martinez A , Bertherat J, Val P
In vivo evidence for the crucial role of SF1 in steroid-producing cells of the testis, ovary and adrenal gland.
Published on 12 Dec 2012 in Development (Cambridge, England) , vol. 139 - pp 4561-70
Buaas FW, Gardiner JR, Clayton S, Val P , Swain A
Transcriptional control of adrenal steroidogenesis: novel connection between Janus kinase (JAK) 2 protein and protein kinase A (PKA) through stabilization of cAMP response element-binding protein (CREB) transcription factor.
Published on 23 Sep 2011 in The Journal of biological chemistry , vol. 286 - pp 32976-85
Lefrancois-Martinez AM , Blondet-Trichard A, Binart N, Val P , Chambon C, Sahut-Barnola I , Pointud JC , Martinez A
Cushing’s syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.
Published on 10 Jun 2010 in PLoS genetics , vol. 6 - pp e1000980
Sahut-Barnola I , de Joussineau C , Val P , Lambert-Langlais S, Damon C, Lefrançois-Martinez AM, Pointud JC , Marceau G , Sapin V , Tissier F, Ragazzon B, Bertherat J, Kirschner LS, Stratakis CA, Martinez A
Gene dosage effects and transcriptional regulation of early mammalian adrenal cortex development.
Published on 08 Jul 2010 in Molecular and cellular endocrinology , vol. 323 - pp 105-14
Val P , Swain A
Constitutive beta-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development.
Published on 15 Apr 2010 in Human molecular genetics , vol. 19 - pp 1561-76
Berthon A , Sahut-Barnola I , Lambert-Langlais S, de Joussineau C , Damon-Soubeyrand C , Louiset E, Taketo MM, Tissier F, Bertherat J, Lefrançois-Martinez AM, Martinez A , Val P
Aldo keto reductase 1B7 and prostaglandin F2alpha are regulators of adrenal endocrine functions.
Published on 07 Oct 2009 in PloS one , vol. 4 - pp e7309
Lambert-Langlais S, Pointud JC , Lefrançois-Martinez AM , Volat F, Manin M, Coudoré F, Val P , Sahut-Barnola I , Ragazzon B, Louiset E, Delarue C, Lefebvre H, Urade Y, Martinez A
The transcription co-factor CITED2 functions during sex determination and early gonad development.
Published on 15 Aug 2009 in Human molecular genetics , vol. 18 - pp 2989-3001
Buaas FW, Val P , Swain A
A transgenic mouse line with specific Cre recombinase expression in the adrenal cortex.
Published on 05 Mar 2009 in Molecular and cellular endocrinology , vol. 300 - pp 197-204
Lambert-Langlais S, Val P , Guyot S, Ragazzon B, Sahut-Barnola I , De Haze A , Lefrançois-Martinez AM , Martinez A
Mouse model for bilateral adrenal hyperplasia.
Published on 30 Jun 2009 in Annales d'endocrinologie , vol. 70 - pp 194
Sahut-Barnola I , De Joussineau C , Val P , Lambert-Langlais S, Lefrançois-Martinez AM , Pointud JC , Marceau G , Sapin V , Ragazzon B, Bertherat J, Kirschner LS, Stratakis CA, Martinez A
Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage.
Published on 30 Jun 2007 in Development (Cambridge, England) , vol. 134 - pp 2349-58
Val P , Martinez-Barbera JP, Swain A
Identification of a novel population of adrenal-like cells in the mammalian testis.
Published on 01 Nov 2006 in Developmental biology , vol. 299 - pp 250-6
Val P , Jeays-Ward K, Swain A
Regulation of the aldo-keto reductase gene akr1b7 by the nuclear oxysterol receptor LXRalpha (liver X receptor-alpha) in the mouse intestine: putative role of LXRs in lipid detoxification processes.
Published on 30 Apr 2004 in Molecular endocrinology (Baltimore, Md.) , vol. 18 - pp 888-98
Volle DH , Repa JJ, Mazur A, Cummins CL, Val P , Henry-Berger J , Caira F , Veyssiere G, Mangelsdorf DJ, Lobaccaro JM
