Team description

Olivier Mignen’s team is located in Brest (INSERM U1078).

 

Our team is deeply involved in studies on calcium signaling and more specifically on calcium influx and its role in cancer.

 

Our research is totally devoted to calcium entry into non-excitable cells. We are characterizing the molecular nature, the regulation and the role of calcium entry in different cell types. Our team has a international and European leading position in the field of store dependent and independent calcium influx supported by Orai proteins and regulated by STIM proteins. In the last few years, we identified and characterized the store independent ARC channels regulated by arachidonic acid and were the first to decipher the molecular architecture of CRAC channels. In addition to our internationally recognized expertise in the field of calcium entry, we developed in our previous studies different molecular tools to explore this entry that will be really beneficial for the success of this project.

Role in the network

Our group brings to the project its knowledge, expertise and skills on Orai channel in the context of LLC and prostate cancer (to decipher the roles of these channels in cancer processes) but also in the identification of new modulators of KCa and Orai channels that have been shown involved in carcinogenesis. It will also provide the various tools it has found to explore the entry of calcium into the cells.

Co-coordinator of task 1 – Olivier Mignen:Role of Ca²⁺ and SK3 channels in cancer cell migration and survival

Involvement in tasks 1, 2, 4, 6

  Role of Ca²⁺ and SK3 channels in cancer cell migration and survival : Characterizing the involvement of Orai, TRPC1/4 and STIM in modulation of Ca²⁺ signalization in chronic lymphocytic leukemia (CLL).

  Clinical relevance of SK3 and Calcium channels (on human tumors) : demonstrate the contribution of these channels or signalplex as new pronostic biomarkers and to evaluate their impact on the therapeutic response or drug side-effects : CLL and prostate cancer.

  Development of cellular models : (Orai channels models and STIM models).

  Involvement in the development of multicentric platform to test new drugs: calcium imaging studies. 

Valorizations/Collaborations

Main collaborations

 

International collaborations

- Trevor Shuttleworth (University of Rochester Medical Center, USA): ARC channels regulation

- Dave Yule (University of Rochester Medical Center, USA): calcium signaling in pancreatic cells

- Miklos Sahin-Toth (Department of Molecular & Cell Biology, Boston University, USA): pancreatitis and calcium signaling.

- Wesley Brooks : University of Florida (USA) : STIM1 modeling and in silico screening ORAI and STIM modulators

- Peter Statopoulhos et Miko Ikura : In vitro analysis of STIM1 properties.

 

European collaborations

- Alexi Tepikin (Department of Physiology, University of Liverpool, England): pancreatitis and calcium signaling.

- Nicolas Demaurex et Maude Frieden: (Geneva Medical University, Switzerland): Modulation of calcium signaling in the endoplasmic reticulum in cells expressing a mutated CFTR .

 

National collaborations

- Bruno Constantin (Institut de Physiologie et Biologie Cellulaires, Université de Poitiers, Poitiers) : Calcium signaling and Leukemia

- Christophe Vandier (INSERM U1069 Nutrition, Croissance et Cancer, Tours): calcium channels and cancer

- Laurent Misery (Laboratoire de neurobiologie Faculté de Médecine, Brest): calcium channels and Merkel cells/ The effects of ciguatoxin on calcium signaling in neurons and keratinocytes.

- Yves Renaudineau (EA2216 Immunologie et pathologies, Faculté de Médecine, Brest) : calcium channels and CLL.

- Thierry Capiod (INSERM U807, Université Paris - Descartes site Necker, Paris): Calcium signaling and cellular proliferation.

- Geneviève Hery-Arnaud (LUBEM, Faculté de Médecine, Brest) : calcium signaling and infection by P. aeruginosa.

- Catherine Pavoine : ICAN - Faculte de Medecine Pierre et Marie Curie : ORAI3 and heart disease.

- Michel De Waard : INSERM U836 (Grenoble) : Identifying ORAI modulators from scorpion venoms.

- Société Affilogic (Nantes): Identification of modulators of the nanofitine type calcium influx

-Yannick Fleury (LUBEM – Quimper) : Identification of bacterial peptide modulators of calcium influx.

- BIODIMAR (LEMAR Brest) : Identifying antioxidant molecules of marine origin modulating calcium influx.

- Aubin Penna (IRSET Rennes) : Study of calcium influx regulated by TRPV2 and ORAI proteins in cancer cells. Identification of TRPV an Orai modulators.

- Jean-Pierre Bazureau (ISCR UMR CNRS 6226, groupe ICMV): Identification of SKF96365 derivatives modulators from ORAI

- François Carreaux (ISCR UMR CNRS 6226,): Identification of modulators of TRPV2 Channels.

- PA Jaffrès, (CNRS 6521 Brest) : Study of the amphiphilic compound effect on calcium influx of B cells.

- S Routier (ICOA, Orléans) et V. Thierry (UMR 7206, La Rochelle) : Study of synthetic origin modulators of calcium signaling of B cells.

 

Publications / Patents

Linked to network

 

Calcium signaling and cell fate: how Ca2+ signals may contribute to wrong decisions for Chronic Lymphocytic Leukemic B lymphocyte outcome? M. Debant, P. Hemon, C. Brigodeau, Y. Renaudineau and O. Mignen. Inter. J. Dev. Biol. 2015 in press.

 

Are Orai1 and Orai3 channels more important than calcium influx for cell proliferation? A.S. Borowiec, G. Bidaux, R. Tacine, P. Dubar, N. Pigat, P. Delcourt, O. Mignen, and T. Capiod. Biochimica et biophysica acta-Molecular Cell Research – 2014; 1843(2):464-72.

 

The ARC Channel-An Endogenous Store-Independent Orai Channel. J.L. Thompson, O. Mignen and T.J. Shuttleworth T. J. Curr Top Membr. 2013; 71:125-48

 

Abnormal Calcium Influx in T and B Lymphocytes from Systemic Lupus Erythematosus Patients is Related to STIM-1 Over-Expression. Y Renaudineau, O Mignen, T Fali, M Burgos, D Cornec, S Jousse. Annals of the Rheumatic Diseases. 2013;72:A30-A30.

 

The N-terminal domain of Orai3 determines selectivity for activation of the ARC channel by arachidonic. acid. J.L. Thompson, O. Mignen and TJ. Shuttleworth Channels (Austin). (2010) Sep-Oct;4(5):398-410

 

The ORAI1 SCID mutation and CRAC channel function in the heterozygous condition. O Mignen, J Thompson, and TJ. Shuttleworth (2009) Journal of Biological Chemistry 284(11):6620-6626

 

Molecular Architecture of Orai1 and Orai3 subunits in the ARC Channel Pore. O Mignen, J.L. Thompson, and TJ. Shuttleworth (2009). Journal of Physiology (London). (2009) 587(Pt 17):4181-97.

 

Brevets

METHOD OF SCREENING OF COMPOUNDS USING MEMBRANE STIM1 BREVET EN EUROPE N°14290232.9 DV2236 - N/Réf : BNT218446EP00

 

« Processes for the diagnosis, prognosis and monitoring of the progression of Chronic Lymphoid Leukaemia (CLL) and/or of Systemic Lupus Erythematosus (SLE) using membrane STIM 1». EP15156694.0 BNT218447EP00

 

Team publication with reading committee

 

Calcium signaling and cell fate: how Ca2+ signals may contribute to wrong decisions for Chronic Lymphocytic Leukemic B lymphocyte outcome? M. Debant, P. Hemon, C. Brigodeau, Y. Renaudineau and O. Mignen. Inter. J. Dev. Biol. 2015 in press.

 

SERCA and PMCA pumps contribute to the deregulation of Ca homeostasis in human CF epithelial cells. Biochimica et biophysica acta. 2015; 1853(5):892-903. R. Philippe, F. Antigny, P. Buscaglia, C. Nore, F. Becq, M. Frieden, O. Mignen.

 

Are Orai1 and Orai3 channels more important than calcium influx for cell proliferation? A.S. Borowiec, G. Bidaux, R. Tacine, P. Dubar, N. Pigat, P. Delcourt, O. Mignen, and T. Capiod. Biochimica et biophysica acta-Molecular Cell Research – 2014; 1843(2):464-72.

 

The ARC Channel-An Endogenous Store-Independent Orai Channel. J.L. Thompson, O. Mignen and T.J. Shuttleworth T. J. Curr Top Membr. 2013; 71:125-48

 

Proteomic Identification of Calumenin as a G551D - CFTR Associated Protein. L. Teng, M, Kerbiriou, M, Taiya, S. Le Hir, O. Mignen, N. Benz, P. Trouvé and C. Férec. PLoS One. 2012;7(6):e40173.

 

Characterization of neurons from adult human skin-derived precursors in serum-free medium : a PCR array and immunocytological analysis. N Lebonvallet N, N Boulais C Le Gall, J Chéret, U Pereira, O Mignen, V Bardey, C Jeanmaire, L Danoux, G Pauly and L Misery L. Exp Dermatol. 2012 Mar;21(3):195-200.

 

High-throughput analysis of promoter occupancy reveals new targets for Arx, a gene mutated in mental retardation and interneuronopathies. ML Quillé, S Carat, S Quéméner-Redon, E Hirchaud, D Baron, C Benech, J Guihot, M Placet, O Mignen, C Férec, R Houlgatte and G Friocourt. PLoS One. 2011;6(9):e25181

 

Sustained calcium signalling and caspase-3 activation involve NMDA receptor in thymocytes in contact with dendritic cells. P Affaticati P, O Mignen, F Jambou, M.C Potier, I Kilngel-Schmitt, J Degrouard, R Liblau, T Capiod and S cohen Kaminsky . Cell Death Differentiation. (2011) Jan;18(1):99-108.

 

The N-terminal domain of Orai3 determines selectivity for activation of the ARC channel by arachidonic. acid. J.L. Thompson, O. Mignen and TJ. Shuttleworth Channels (Austin). (2010) Sep-Oct;4(5):398-410

 

The ORAI1 SCID mutation and CRAC channel function in the heterozygous condition. O Mignen, J Thompson, and TJ. Shuttleworth (2009) Journal of Biological Chemistry 284(11):6620-6626.

 

Molecular Architecture of Orai1 and Orai3 subunits in the ARC Channel Pore. O Mignen, J.L. Thompson, and TJ. Shuttleworth (2009). Journal of Physiology (London). (2009) 587(Pt 17):4181-97.