Professor Natalia Prevarskaya is in charge of the Cell Physiology Laboratory at the University of Lille1, Inserm U1003, France. This team is a member of the French national channelopathies network, ICST (Ion Channel Science and Therapeutics), within the framework of the national call for LabEx “Laboratories of Excellence” projects (2012-2020), developed for the systematic approach to identifying and validating ion channel proteins and modulators as novel drug targets and/or biomarkers appropriate for therapeutic and diagnostic use.The team directed by N.Prevarskaya is one of the pioneers in the field of “Ion channels and cancer”. Over these last few years, they have focused their attention on the identification and characterisation of ion channels playing important roles in prostate (and later pancreatic) cancer hallmarks such as 1) self-sufficiency in growth signals and aberrant cell proliferation, 2) insensitivity to antigrowth signals, 3) evasion of programmed cell death (apoptosis), and 4) tissue invasion and metastasis. Furthermore, they engaged efforts to establish “calcium and ion channels signatures” for prostate and pancreatic cancer staging in order to develop reliable prognostic markers and in order to order to develop reliable prognostic markers and define new therapeutic treatment strategies. The main methods employing by this team are the modern molecular electrophysiology and calcium imaging techniques, which are essential to the project (a patch clamp for recording the activity of ‘unitary channels’, a system for measuring exocytosis in single cells, two calcium imaging installations and an electrophysiology set-up combined with a confocal microscope have been installed in the laboratory in recent years). Laboratory is equipped with a “High throughput electrophysiological screening” platform comprising the “Flyion”set-up , the Nanion technologies “Port-A-Patch” and 4 conventional patch-clamp set-ups.IonTraC projects:ORAI & TRP channels in apoptosis, ER stress and autophagyORAI & TRP channels in PDAC cell migration and invasionHomepageRelevant publications:1. Dubois C, Vanden Abeele F, Lehen'kyi V, Gkika D, Guarmit B, Lepage G., Slomianny C, Borowiec AS, Bidaux G, Benahmed M, Shuba Y, Prevarskaya N. Remodeling of channel-forming ORAI proteins determines an oncogenic switch in prostate cancer. Cancer Cell. 2014 Jul 14;26(1):19-32.2. Raphaël M, Lehen'kyi V, Vandenberghe M, Beck B, Khalimonchyk S, Vanden Abeele F, Farsetti L, Germain E, Bokhobza A, Mihalache A, Gosset P, Romanin C, Clézardin P, Skryma R, Prevarskaya N. TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival. Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):E3870-9. 3. Vandenberghe M, Raphaël M, Lehen'kyi V, Gordienko D, Hastie R, Oddos T, Rao A, Hogan PG, Skryma R, Prevarskaya N. ORAI1 calcium channel orchestrates skin homeostasis. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):E4839-48..4. Shapovalov G, Gkika D, Devilliers M, Kondratskyi A, Gordienko D, Busserolles J, Bokhobza A, Eschalier A, Skryma R, Prevarskaya N. Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8. Cell Reports. 2013 Aug 15;4(3):504-15. doi: 10.1016/j.celrep.2013.07.002.5. Prevarskaya N, Skryma R, Shuba Y. Calcium in tumour metastasis: new roles for known actors. Nature Reviews Cancer. 2011 Jul 22;11(8):609-18. doi: 10.1038/nrc3105. 6. G Bidaux, M Flourakis, S Thebault, A Zholos, B Beck, D Gkika, M Roudbaraki, JL Bonnal, B.Mauroy, Y Shuba, R Skryma, and N Prevarskaya. Differentiation status of prostate cells determines TRPM8 channel subcellular localization and function: involvement in carcinogenesis. J. Clin. Invest., 2007, 10.1172
