CV Science

Patrick LEGEMBRE Ph.D Onco-Immunology

Course and current status

Present address:

• UMR CNRS 7276 - Inserm U1262; Faculté de Médecine – 2 rue du Dr Marcland 87025 – Limoges Cedex.
• Phone: (+33)-519 56 42 82
  
• E-mail: patrick.legembre@inserm.fr
  
• Key works: CD95/Fas, lupus, triple negative breast cancer, inflammation, TNF receptors, apoptosis, calcium.

Education 

• 2007- Habilitation to supervise research (HDR); University of Bordeaux; Immunology/Oncology.
• 2002- Ph.D.; University of Bordeaux; Immunology/Oncology.

Employments

• Nov 2019- now: Director of Research Inserm (Professor), UMR CNRS 7276 - Inserm U1262; Limoges/France. 
• Jan 2017- Oct 2019: Deputy Director U1242, CLCC Eugène Marquis, Ligue Contre Le cancer Team. Rennes/France.
• Jan 2015- Dec 2016- Director ER440. CLCC Eugène Marquis, Ligue Contre Le cancer Team. Rennes/France.
• Jan 2010-Dec 2014- Director of Research Inserm (Professor), U1085. Rennes/France.
• Dec 2005-Dec 2009- Associate Professor (CR INSERM), UMR CNRS 5164 (Pr. Moreau JF). Bordeaux/France.
• Sept 2002-Oct 2005- Postdoctoral fellow, (Pr Peter M). Ben May Institute For Cancer Research/ University of Chicago. Chicago/USA.

Patents

2010. WO2010063847; 2014. WO2014118317; 2015. WO2015189236; 2015. WO2015044229; 2015. WO2015158810; 2015. WO2015104284; 2017. WO2017149012; 2018. WO2018130679; 2023. WO2023161412A1; 2023. WO2023099578A1

Scientific Academy Society and committees membership

• Member of National Scientific Council CNRS-CSI. Institut des sciences biologiques (INSB) (2024-2029)
• Member of National Ligue Contre Le Cancer Scientific Council (2013-2017)
• Member of National INSERM scientific council-CSS2 (2008-2012)
• Associate editor of the journal Recent Patents on Anti-Cancer Drug Discovery. (2009-2018)
• Editorial board member of Anti-Cancer Drugs (2010-present); Int. J. Oncology (2021-present) and Frontiers in Molecular Medicine (2021-present)

Awards

• 2019: Price “Jean Valade” Fondation de France.
  
• 2016: Price “Ruban Rose Avenir”.
• 2016: Price “Fondation Banque Populaire de l’Ouest Avenir”.
• 2012-2017: Equipe “Ligue Contre Le Cancer”.
• 2007-2012: ANR young scientist.

PUBLICATIONS (10 main publications over 91; according Web of Science h-index:28).

1. Liu M, Huang C, Zhou X, Jiang C, Liu S, Gao Y, Kuang L, Lei Z, Jia R, Xu J, Legembre P*, Liang X*. Membrane-bound CD95 ligand modulates CD19-mediated B cell receptor signaling and EBV activation. J Med Virol. 2024. doi: 10.1002/jmv.29440. *Co-Last Authors.
2. Kenji SF, Kurma K, Collet B, Oblet C, Debure L, Di Primo C, Minder L, Vérité F, Danger Y, Jean M, Penna A, Levoin N, Legembre P. MMP7 cleavage of amino-terminal CD95 death receptor switches signaling toward non-apoptotic pathways. Cell Death Dis. 2022. doi: 10.1038/s41419-022-05352-0.
3. Poissonnier A, Guégan JP, Nguyen HT, Best D, Levoin N, Kozlov G, Gehring K, Pineau R,, Jouan F,, Morere L,, Martin S, Thomas M, Lazaro E, Douchet I, Ducret T, van de Weghe P, Blanco P, Jean M, Vacher P and Legembre P. Disrupting the CD95-PLCγ1 interaction prevents Th17-driven inflammation. Nature Chemical Biology. 2018. doi: 10.1038/s41589-018-0162-9.
4. Poissonnier A, Sanséau D, Le Gallo M, Malleter M, Levoin N, Viel R, Morere L, Penna A, Blanco P, Dupuy A, Poizeau F, Fautrel A, Seneschal J, Jouan F, Ritz J, Forcade E, Rioux N, Contin C, Ducret T, Vacher A-M, Barrow PA, Flynn RJ, Vacher P, and Legembre P. CD95-Mediated Calcium Signaling Promotes T Helper 17 Trafficking to Inflamed Organs in Lupus-Prone Mice. Immunity. 2016. doi: 10.1016/j.immuni.2016.06.028. 
5. Malleter M, Tauzin S, Bessede A, Castellano R, Goubard A, Godey F, Levêque J, Jézéquel P, Campion L, Campone M, Ducret T, MacGrogan G, Debure L, Collette Y, Vacher P, Legembre P. CD95L cell surface cleavage triggers a prometastatic signaling pathway in triple-negative breast cancer. Cancer Res. 2013. doi: 10.1158/0008-5472.CAN-13-1794.
6. Khadra N, Bresson-Bepoldin L, Penna A, Chaigne-Delalande B, Ségui B, Levade T, Vacher AM, Reiffers J, Ducret T, Moreau JF, Cahalan MD, Vacher P, Legembre P. CD95 triggers Orai1-mediated localized Ca2+ entry, regulates recruitment of protein kinase C (PKC) β2, and prevents death-inducing signaling complex formation. PNAS. 2011. doi: 10.1073/pnas.1116946108.
7. Tauzin S, Chaigne-Delalande B, Selva E, Khadra N, Daburon S, Contin-Bordes C, Blanco P, Le Seyec J, Ducret T, Counillon L, Moreau JF, Hofman P, Vacher P and Legembre P. The naturally processed CD95L elicits a c-yes/calcium/PI3K-driven cell migration pathway. PLoS Biology. 2011. doi: 10.1371/journal.pbio.1001090.
8. Bénéteau M, Daburon S, Moreau JF, Taupin JL, Legembre P. Dominant-negative Fas mutation is reversed by down-expression of c-FLIP. Cancer Res. 2007 Jan 1;67(1):108-15. doi: 10.1158/0008-5472.CAN-06-1415.
9. Legembre P, Barnhart BC, Zheng L, Vijayan S, Straus SE, Puck J, Dale JK, Lenardo M, Peter ME. Induction of apoptosis and activation of NF-kappaB by CD95 require different signalling thresholds. EMBO Rep. 2004. doi: 10.1038/sj.embor.7400280.
10. Barnhart BC*, Legembre P*, Pietras E, Bubici C, Franzoso G, Peter ME. CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells. EMBO J. 2004. doi: 10.1038/sj.emboj.7600325. *Co-First Authors.

CONFERENCE ORGANIZATION

Organizer of International Congress “Cancer Cell Death and Therapy 2017”, St. Malo (France), May 10-12, 2017.

Organizer of 1st International Congress “Cell Death in Cancer”, St. Malo (France), May 13-16, 2012.

Scientific summary

CD95 (also known as Fas) is a death receptor that belongs to the TNF (tumor necrosis factor) receptor superfamily. Its ligand, CD95L is a transmembrane cytokine (m-CD95L), which can be cleaved by metalloproteases and released in the bloodstream as a soluble fragment (s-CD95L). While m-CD95L is found at the surface of immune cells (T cells and NK cells) where it orchestrates the elimination of transformed/infected cells and the immune contraction, s-CD95L is a pro-inflammatory cytokine that enhances the risk of metastatic occurrence in triple negative breast cancers and contributes to the severity of autoimmune disorders including lupus.

Our main goals are i) to decipher how CD95 switches from implementing cell death to non-apoptotic signaling pathways, ii) to identify the cells whose function is deregulated by the naturally processed ligand in breast cancer and lupus and iii) to develop original therapeutics that selectively inhibit the CD95-mediated non-apoptotic and pro-inflammatory signaling pathway.