Patrick Legembre is a French researcher specializing in triple negative breast cancer and systemic lupus erythematosus, with a robust educational and professional background in immunology and oncology. He has authored multiple patents and scientific publications, and currently directs research at Inserm while leading a biotech company focused on therapeutic innovations targeting the CD95/CD95L pathway. His research aims to understand the dual roles of CD95 in promoting both apoptosis and non-apoptotic signaling, particularly in cancer progression and chronic inflammation.

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CURRICULUM VITAE
Patrick Legembre
1974, november 1st (France). 45 years old. Nationality: French. Married, Two kids.
Present address:
INSERM U1262
Rue du Pr. Bernard Descottes
87 025 Limoges Cedex
Phone:(+33)-6-68207640 / E-mail: patrick.legembre@inserm.fr or plegembre@hotmail.com
Key words: triple negative breast cancer, lupus, inflammation, death receptors, PI3K, migration,
therapy, Th17 cells.
EDUCATION
Date Degree Institution Subject
2007 Habilitation to supervise
research (HDR)
University of Bordeaux Immunology/Oncology
2002 Ph.D. degree University of Bordeaux Immunology/Oncology
EMPLOYMENT
Date Title Organization City/Country
Nov 2019-
Present
Senior INSERM
(Director of Researcher)
UMR CNRS 7276 – INSERM U1262 Limoges/France
Jan 2017 Co-founder of APOFAS-
biotech & CSO.
APOFAS-Biotech: spin-off developing
therapeutic drugs targeting Fas/FasL
pathway.
Rennes / France
Jan 2017- Oct
2019
Cancer Center Eugène
Marquis
Deputy Director U1242-
COSS
U1242 INSERM/ Cancer Center
Eugene Marquis/ University Rennes-1
Rennes/France
Jan 2015-
present
Cancer Center Eugène
Marquis
Director ER440 -OSS
Cancer Center Eugene Marquis/
University Rennes-1
Rennes/France
Jan 2010- Dec
2014
Senior INSERM
(Director of Researcher)
U1085 INSERM/ University Rennes-1 Rennes/France
Dec 2005-Dec
2009
Junior INSERM
(Researcher)
University of Bordeaux/ UMR CNRS
5164.
Bordeaux/Franc
e
Sept 2002-Nov
2005
Postdoctoral fellow,
(Pr Peter M).
Ben May Institute For Cancer
Research/ University of Chicago.
Chicago/USA
PATENTS
2010. WO2010063847 - Compositions for potentiating apoptosis signals in tumour cells.
2014. WO2014118317- Methods for predicting and preventing metastasis in triple negative breast cancers
2015. WO2015189236 - Methods and pharmaceutical compositions for reducing cd95-mediated cell motility
2015. WO2015044229 - New PI3K/AKT/mTOR inhibitors and pharmaceutical uses thereof.
2015. WO2015158810 - Polypeptides and uses thereof for reducing cd95-mediated cell motility
2015. WO2015104284 - Methods and pharmaceutical compositions for preventing or reducing metastatic
dissemination
2017. WO2017149012 - Peptides and uses thereof for reducing cd95-mediated cell motility
2018. WO2018130679 - Procédés et compositions pharmaceutiques pour réduire la motilité cellulaire
médiée par cd95
SCIENTIFIC ACADEMY SOCIETY AND COMMITTEES MEMBERSHIP
- Member of National Scientific Council Ligue Contre Le Cancer National (2013-Present)

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- Member of National Scientific Council INCa PLBIO (2017, 2019)
- Member of National Scientific council INSERM -CSS2 (2008-2012)
- Associate editor of the journal Recent Patents on Anti-Cancer Drug Discovery. (2009-2018)
HONORS and AWARDS
2018: Prize “Jean Valade”, Fondation de France.
2016: Prize “Ruban Rose Avenir”.
2016: Prize “Fondation Banque Populaire de l’Ouest Avenir”.
2007-2012: ANR young scientist.
Five main PUBLICATIONS (based on scopus, 62 publications, h=23)
1. 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. Nature Chemical Biology. 2018.
2. 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. Immunity. 2016.
Highlighted in Nature Reviews Rheumatology - Systemic lupus erythematosus - New role for CD95L in TH17
cell recruitment.
3. 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. PNAS. 2011.
Highlighted in Science Signaling - Applying the Brakes with Calcium.
4. 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. PLoS Biology. 2011.
5. Barnhart BC*, Legembre P*, Pietras E, Bubici C, Franzoso G, Peter ME. EMBO J. 2004. * Co-first
authors.
CONFERENCE ORGANIZATION
Co-organizer of 1st International Congress “Cell Death in Cancer”, St. Malo (France), May 13-16, 2012.
Co-organizer of 2sd International Congress “Cancer Cell Death and Therapy”, St. Malo (France), May 10-12,
2017.
Scientific Summary
CD95 (also known as Fas) is considered as a death receptor and it belongs to the TNF (tumor necrosis factor)
receptor family. 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 where it orchestrates the elimination of transformed/infected cells and the
immune contraction, s-CD95L behaves as a proto-oncogene enhancing the risk of metastatic occurrence in
breast cancers. 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 cancers and iii) to develop original therapeutics that selectively inhibit the CD95-mediated
non-apoptotic and pro-inflammatory signaling pathway.

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Resume
Title: Development of drugs selectively inhibiting the non-apoptotic CD95 / Fas signaling pathway in
systemic lupus erythematosus and triple negative breast cancer.
My PhD was conducted under the supervision of Pr. Jean-Luc Taupin in Bordeaux (France), where I studied
the role of CD95/CD95L pair in immune homeostasis. CD95, also known as Fas is a death receptor that belongs
to the Tumor Necrosis family (TNF) receptor family. In the presence of its ligand designated CD95L or FasL,
CD95 implements an apoptotic signalling pathway contributing to the immune surveillance and immune
tolerance 1-4
. Then, I joined Pr. Marcus Peter’s laboratory at University of Chicago (2002-2005, Chicago, USA)
where we established that the stimulation of CD95 in cancer cells resistant to the CD95-mediated apoptotic
signalling pathway, promoted carcinogenesis through the induction of non-apoptotic signals 5-7
. In 2005, I have
been hired as an Assistant professor by INSERM (“chargé de recherche” Inserm from 2005 to 2012, France).
INSERM is a National health research institute operating under the French Ministries of Health and Research.
In Bordeaux, I created my research group and established that anti-tumour agents induced rapid redistribution
of CD95 into lipid rafts to facilitate the implementation of the apoptotic signalling pathway and the elimination
of malignant cells 8,9
.
In 2010, I moved to University of Rennes (Rennes, France) and as a “director of research” Inserm (Full
Professor) joined the Comprehensive Cancer Center Eugène Marquis in Rennes (France) to create an INSERM
Unit working on death receptors, inflammation and tumor adaptation. CD95L belongs to the TNF superfamily
and this transmembrane cytokine can be shed by metalloproteases to release in bloodstream a soluble ligand
(s-CD95L). Our work highlighted that s-CD95L i) is increased in systemic lupus erythematosus (SLE) and
triple negative breast cancer (TNBC) patients and ii) participates in the severity of these pathologies by
promoting the Th17 trafficking in the inflamed organs 10,11
or the metastatic dissemination of TNBC cells,
respectively 12
. In addition, my Team demonstrated that in the presence of s-CD95L, CD95 elicits the formation
of a molecular complex that we termed MISC, for Motility-Inducing Signalling Complex, thereby inducing a
non-orthodox c-yes/Orai1/Ca2+
/PI3K signalling pathway 10,12,13
. Currently, my group including surgeons,
clinicians, biologists, chemists and scientists is interested to understand how the “apoptotic receptor” CD95
participates in the aggravation of the clinical outcomes in chronic inflammatory disorders 10,11,13
and breast
cancers 12,14
. In collaboration with chemists and modelers, we recently synthesized original peptidomimetics
selectively inhibiting the CD95-mediated pro-inflammatory response without affecting its apoptotic signal,
which is instrumental in controlling the immune response 15
. In parallel, I founded a company called APOFAS-
Biotech (2017), which aims at accompanying the original CD95 inhibitors whose therapeutic activity has been
validated in different lupus-prone animal models to clinical trials.
My main goals are now i) to decipher how as a unique receptor, CD95 can induce a such broad-spectrum
of signalling pathways and ii) to evaluate the therapeutic activity of our CD95-targeting inhibitors in
lupus and TNBC mouse models.

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Main publications
60 published papers, H factor: 23 (https://www.scopus.com/authid/detail.uri?authorId=6602336451)
1. 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. Nature Chemical Biology. 2018. IF: 13.8
2. Le Gallo M, Poissonnier A, Blanco P, Legembre P. CD95/Fas, Non-Apoptotic Signaling Pathways,
and Kinases. Front Immunol. 2017. IF: 6.4
3. 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-Bordes C, Ducret T,
Vacher AM, Barrow PA, Flynn RJ, Vacher P, Legembre P. CD95-Mediated Calcium Signaling Promotes T
Helper 17 Trafficking to Inflamed Organs in Lupus-Prone Mice. Immunity. 2016. IF:22.8
4. Fouqué A, Lepvrier E, Debure L, Gouriou Y, Malleter M, Delcroix V, Ovize M, Ducret T, Li C,
Hammadi M, Vacher P, Legembre P. The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote
cell migration by inducing Ca(2+) flux from the endoplasmic reticulum to mitochondria. Cell Death Differ.
2016. IF:8
5. Monet M, Poët M, Tauzin S, Fouqué A, Cophignon A, Lagadic-Gossmann D, Vacher P, Legembre
P*, Counillon L*. The cleaved FAS ligand activates the Na(+)/H(+) exchanger NHE1 through Akt/ROCK1 to
stimulate cell motility. Sci Rep. 2016. IF:4.2
*Co-last authors.
6. Fouqué A, Delalande O, Jean M, Castellano R, Josselin E, Malleter M, Shoji KF, Hung MD,
Rampanarivo H, Collette Y, van de Weghe P, Legembre P. A Novel Covalent mTOR Inhibitor, DHM25,
Shows in Vivo Antitumor Activity against Triple-Negative Breast Cancer Cells. J Med Chem. 2015. IF: 6.2
7. Edmond V, Dufour F, Poiroux G, Shoji K, Malleter M, Fouqué A, Tauzin S, Rimokh R, Sergent O,
Penna A, Dupuy A, Levade T, Theret T, Micheau O, Ségui B, and Legembre P. Down-regulation of ceramide
synthase-6 during epithelial-to-mesenchymal transition reduces plasma membrane fluidity and cancer cell
motility. Oncogene. 2015. IF:6.8
8. Fouqué A, Debure L, Legembre P. The CD95/CD95L signaling pathway: A role in carcinogenesis.
BBA. Reviews on Cancer. 2014. Review. IF:8.2
9. Malleter M, Tauzin S, Bessede A, Castellano R, Goubard A, Godey F, Leveque J, Jezequel P, Campion
L, Campone M, Ducret T, Macgrogan G, Debure L, Collette Y, Vacher P, Legembre P. CD95L cell surface
cleavage triggers a pro-metastatic signaling pathway in triple negative breast cancer. Cancer Res. IF:9.2
10. Tauzin S, Debure L, Moreau JF, Legembre P. CD95-mediated cell signaling in cancer: mutations and
post-translational modulations. Cell Mol Life Sci. 2012. Review. IF:6.7
11. Klionsky DJ, et al., Guidelines for the use and interpretation of assays for monitoring autophagy.
Autophagy. 2012. IF: 11.1
12. 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. Proc Natl Acad Sci USA. 2011. IF: 9.6
13. 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, Legembre P. The naturally processed CD95L
elicits a c-yes/calcium/PI3K-driven cell migration pathway. PLoS Biol. 2011. IF: 9.1
14. Pizon M, Rampanarivo H, Tauzin S, Chaigne-Delalande B, Daburon S, Castroviejo M, Moreau P,
Moreau JF, Legembre P. Actin-independent exclusion of CD95 by PI3K/AKT signalling: implications for
apoptosis. Eur J Immunol. 2011. IF: 4.2
15. Leon-Bollotte L, Subramaniam S, Cauvard O, Plenchette-Colas S, Paul C, Godard C, Martinez-Ruiz
A, Legembre P, Jeannin JF, Bettaieb A. S-nitrosylation of the death receptor fas promotes fas ligand-mediated
apoptosis in cancer cells. Gastroenterology. 2011. IF: 20.7
16. Chaigne-Delalande B, Mahfouf W, Daburon S, Moreau JF, Legembre P. CD95 engagement mediates
actin-independent and -dependent apoptotic signals. Cell Death Differ. 2009. IF: 8
17. Chaigne-Delalande B, Guidicelli G, Couzi L, Legembre P. An atypical necrotic signal induced by
immunosuppressive and anti-viral agents. Autophagy. 2009. IF: 11.1
18. Chaigne-Delalande B, Guidicelli G, Couzi L, Merville P, Mahfouf W, Bouchet S, Molimard M, Pinson
B, Moreau JF, Legembre P. The immunosuppressor mycophenolic acid kills activated lymphocytes by
inducing a nonclassical actin-dependent necrotic signal. J Immunol. 2008. IF: 4.8

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19. Bénéteau M, Pizon M, Chaigne-Delalande B, Daburon S, Moreau P, De Giorgi F, Ichas F, Rebillard
A, Dimanche-Boitrel MT, Taupin JL, Moreau JF, Legembre P. Localization of Fas/CD95 into the lipid rafts
on down-modulation of the phosphatidylinositol 3-kinase signaling pathway. Mol Cancer Res. 2008. IF: 4.6
20. Schembri L, Dalibart R, Tomasello F, Legembre P, Ichas F, De Giorgi F. The HA tag is cleaved and
loses immunoreactivity during apoptosis. Nat Methods. 2007. IF: 26.9
21. 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. IF :9.2
22. Legembre P, Daburon S, Moreau P, Moreau JF, Taupin JL. Modulation of Fas-mediated apoptosis by
lipid rafts in T lymphocytes. J Immunol. 2006. IF: 4.8
23. Legembre P, Daburon S, Moreau P, Ichas F, de Giorgi F, Moreau JF, Taupin JL. Amplification of
Fas-mediated apoptosis in type II cells via microdomain recruitment. Mol Cell Biol. 2005. IF: 3.8
24. Peter ME, Legembre P, Barnhart BC. Does CD95 have tumor promoting activities? BBA. Reviews
on Cancer. 2005. Review. IF:8.2
25. 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. IF: 8.7
26. Legembre P, Schickel R, Barnhart BC, Peter ME. Identification of SNF1/AMP kinase-related kinase
as an NF-kappaB-regulated anti-apoptotic kinase involved in CD95-induced motility and invasiveness. J
Biol Chem. 2004. IF: 4.1
27. 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. * co-first authors. IF: 10.5
28. Legembre P, Beneteau M, Daburon S, Moreau JF, Taupin JL. Cutting edge: SDS-stable Fas
microaggregates: an early event of Fas activation occurring with agonistic anti-Fas antibody but not with Fas
ligand. J Immunol. 2003. IF: 4.8
29. Algeciras-Schimnich A, Pietras EM, Barnhart BC, Legembre P, Vijayan S, Holbeck SL, Peter ME.
Two CD95 tumor classes with different sensitivities to antitumor drugs. Proc Natl Acad Sci U S A. 2003.
IF: 9.6
30. Legembre P, Moreau P, Daburon S, Moreau JF, Taupin JL. Potentiation of Fas-mediated apoptosis
by an engineered glycosylphosphatidylinositol-linked Fas. Cell Death Differ. 2002. IF: 8
31. Taupin JL, Legembre P, Bitard J, Daburon S, Pitard V, Blanchard F, Duplomb L, Godard A, Jacques
Y, Moreau JF. Identification of agonistic and antagonistic antibodies against gp190, the leukemia inhibitory
factor receptor, reveals distinct roles for its two cytokine-binding domains. J Biol Chem. 2001. IF: 4.1