Onco Pheno Screen Platform

Research director Guido Kroemer
Co-director: Oliver Kepp, Allan Sauvat, Giulia Cerrato

Contact details

OncoPhenoScreen platform, 15 Rue de l'École de Médecine, 75006 Paris

Tel. office: +33(0)1 42 11 45 16

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Team members:

- Managing director : Oliver KEPP

- Technical director : Allan SAUVAT

- Communications director : Giulia CERRATO

- Lab manager : Sabrina FORVEILLE

- Data Scientists : Marion LEDUC

- Scientific engineer : Liwei ZHAO

Summary of the research topics :

The OncoPhenoScreen platforms work in concert with INSERM UMR1138 “Metabolism, CANCER & IMMUNITY” to investigate the molecular and cellular mechanisms of cell stress and cell death in the cancer immune dialogue. The mode of cellular stress and death that is evoked during cancer treatment has profound therapeutic implications. A systematic search has been launched to identify molecular switches that “decide” which particular cell stress or cell death subroutine is preferentially executed. In addition, cancer cell death modalities and their impact on the immune system are analyzed in a systematic fashion to develop strategies that improve the chances of therapeutic success.
The OncoPhenoScreen platform is used as a hub to conduct screening approaches, as it offers fully automated cell biology workflows that allow for 3D-phenotypic screening of large-scale compound and genetic libraries necessary to conduct systems biology oriented research. The design of the platform allows for extremely flexible assay design and multiplexing as it integrates automated cell culture and compound management with fully automated high content analysis systems via industrial robots.

Keywords:

High throughput compound and siRNA screening; imaging; biosensors; cell death

Selected publications:

• Pan H, Tian AL, Chen H, Xia Y, Sauvat A, Moriceau S, Lambertucci F, Motiño O, Zhao L, Liu P, Mao M, Li S, Zhang S, Joseph A, Durand S, Aprahamian F, Luo Z, Ou Y, Shen Z, Xue E, Pan Y, Carbonnier V, Stoll G, Forveille S, Leduc M, Cerrato G, Cerone A, Maiuri MC, Castinetti F, Brue T, Wang H, Ma Y, Martins I, Kepp O, Kroemer G. Pathogenic role of acyl coenzyme A binding protein (ACBP) in Cushing's syndrome. Nat Metab. 2024 Nov 22.
• Hofer SJ, Daskalaki I, Bergmann M, Friščić J, Zimmermann A, Mueller MI, Abdellatif M, Nicastro R, Masser S, Durand S, Nartey A, Waltenstorfer M, Enzenhofer S, Faimann I, Gschiel V, Bajaj T, Niemeyer C, Gkikas I, Pein L, Cerrato G, Pan H, Liang Y, Tadic J, Jerkovic A, Aprahamian F, Robbins CE, Nirmalathasan N, Habisch H, Annerer E, Dethloff F, Stumpe M, Grundler F, Wilhelmi de Toledo F, Heinz DE, Koppold DA, Rajput Khokhar A, Michalsen A, Tripolt NJ, Sourij H, Pieber TR, de Cabo R, McCormick MA, Magnes C, Kepp O, Dengjel J, Sigrist SJ, Gassen NC, Sedej S, Madl T, De Virgilio C, Stelzl U, Hoffmann MH, Eisenberg T, Tavernarakis N, Kroemer G, Madeo F. Spermidine is essential for fasting-mediated autophagy and longevity. Nat Cell Biol. 2024 Sep;26(9):1571-1584.
• Zhao L, Liu P, Mao M, Zhang S, Bigenwald C, Dutertre CA, Lehmann CHK, Pan H, Paulhan N, Amon L, Buqué A, Yamazaki T, Galluzzi L, Kloeckner B, Silvin A, Pan Y, Chen H, Tian AL, Ly P, Dudziak D, Zitvogel L, Kepp O, Kroemer G. BCL2 Inhibition Reveals a Dendritic Cell-Specific Immune Checkpoint That Controls Tumor Immunosurveillance. Cancer Discov. 2023 Nov 1;13(11):2448-2469.
• Zhang S, Zhao L, Guo M, Liu P, Li S, Xie W, Tian AL, Pol JG, Chen H, Pan H, Mao M, Li Y, Zitvogel L, Jin Y, Kepp O, Kroemer G. Anticancer effects of ikarugamycin and astemizole identified in a screen for stimulators of cellular immune responses. J Immunother Cancer. 2023 Jul;11(7):e006785.
• Fidelle M, Rauber C, Alves Costa Silva C, Tian AL, Lahmar I, de La Varende AM, Zhao L, Thelemaque C, Lebhar I, Messaoudene M, Pizzato E, Birebent R, Mbogning Fonkou MD, Zoppi S, Reni A, Dalban C, Leduc M, Ferrere G, Durand S, Ly P, Silvin A, Mulder K, Dutertre CA, Ginhoux F, Yonekura S, Roberti MP, Tidjani- Alou M, Terrisse S, Chen J, Kepp O, Schippers A, Wagner N, Suárez-Gosálvez J, Kobold S, Fahrner JE, Richard C, Bosq J, Lordello L, Vitali G, Galleron N, Quinquis B, Le Chatelier E, Blanchard L, Girard JP, Jarry A, Gervois N, Godefroy E, Labarrière N, Koschny R, Daillère R, Besse B, Truntzer C, Ghiringhelli F, Coatnoan N, Mhanna V, Klatzmann D, Drubay D, Albiges L, Thomas AM, Segata N, Danlos FX, Marabelle A, Routy B, Derosa L, Kroemer G, Zitvogel L. A microbiota- modulated checkpoint directs immunosuppressive intestinal T cells into cancers. Science. 2023 Jun;380(6649):eabo2296.
• Yonekura S, Terrisse S, Alves Costa Silva C, Lafarge A, Iebba V, Ferrere G, Goubet AG, Fahrner JE, Lahmar I, Ueda K, Mansouri G, Pizzato E, Ly P, Mazzenga M, Thelemaque C, Fidelle M, Jaulin F, Cartry J, Deloger M, Aglave M, Droin N, Opolon P, Puget A, Mann F, Neunlist M, Bessard A, Aymeric L, Matysiak-Budnik T, Bosq J, Hofman P, Duong CPM, Ugolini S, Quiniou V, Berrard S, Ryffel B, Kepp O, Kroemer G, Routy B, Lordello L, Bani MA, Segata N, Yengej FY, Clevers H, Scoazec JY, Pasolli E, Derosa L, Zitvogel L. Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis. Cancer Discov. 2022 Apr 1;12(4):1128-1151. 
• Pihán P, Lisbona F, Borgonovo J, Edwards-Jorquera S, Nunes-Hasler P, Castillo K, Kepp O, Urra H, Saarnio S, Vihinen H, Carreras-Sureda A, Forveille S, Sauvat A, De Giorgis D, Pupo A, Rodríguez DA, Quarato G, Sagredo A, Lourido F, Letai A, Latorre R, Kroemer G, Demaurex N, Jokitalo E, Concha ML, Glavic Á, Green DR, Hetz C. Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1. Sci Adv. 2021 Nov 12;7(46):eabe5469. 
• Zhao L, Liu P, Xie W, Zhang S, Thieme S, Zitvogel L, Kroemer G, Kepp O. A genotype-phenotype screening system using conditionally immortalized immature dendritic cells. STAR Protoc. 2021 Aug 12;2(3):100732.
• Wu Q, Tian AL, Li B, Leduc M, Forveille S, Hamley P, Galloway W, Xie W, Liu P, Zhao L, Zhang S, Hui P, Madeo F, Tu Y, Kepp O, Kroemer G. IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms. J Immunother Cancer. 2021 Jun;9(6):e002722. 
• Kepp O, Bezu L, Yamazaki T, Di Virgilio F, Smyth MJ, Kroemer G, Galluzzi L. ATP and cancer immunosurveillance. EMBO J. 2021 Jul 1;40(13):e108130.