CV Science

Elise Chiffoleau CR1 INSERM

Course and current status

E. Chiffoleau completed her Ph.D. degree (1999-2002) in UMR Nantes-INSERM on the identification and characterization of new molecules involved in allograft tolerance. She performed a postdoctoral position (2002-2003) at the University of Pennsylvania, Philadelphia, in the laboratory of Dr. Laurence Turka. Her research was on the study of the mechanisms and molecular pathways of molecules (TRAF6, BclXL, Notch) involved in allograft or self-tolerance. She then obtained a permanent position at the UMR 1064 (University of Nantes, Inserm, CNRS). E. Chiffoleau belogs to team 1 of UMR1064 Center for Research in Transplantation and Immunology (CRTI) (http://crti.univ-nantes.fr/) that is a joint research unit created by INSERM and Université de Nantes in 2012 and renewed in 2017. CRTI is historically the evolution of previous units devoted to transplant immunology for almost 20 years in Nantes and constitutes with several clinical departments the Institute of Transplantation Urology and Nephrology (ITUN), one of the largest French and European kidney transplantation centers. CRTI gathers researchers and clinicians with expertise in basic immunology, transplantation, autoimmunity, inflammation, virology, nephrology, regenerative medicine, genetic and bioinformatics and who develop innovative projects going from basic to clinical research. Her team is interested in understanding the cellular and molecular mechanisms of immunoregulation in the context of organ transplantation, immune-mediated inflammatory diseases (IMIDs) and immune response to persistent virus. They aim to identify new immunoregulatory cellular and molecular targets and to translate these findings for clinical application as innovative therapeutics or biomarkers.

PATENTS
-Methods and pharmaceutical compositions for promoting T cells response, EP16306381 21/10/2016 (filed patent WO/2018/073440, co-assignment to OSEImmunotherapeutics).
-Methods for the detection of cells and molecules interacting with receptor CLEC-1, in particular for the detection of CLEC-1 endogenous ligand, EP 19306584.4 05/12/2019.
-Anti-CLEC-1 antibodies and antigen-binding fragment thereof, EP 19306583.6 05/12/2019.

PEDAGOGICAL RESPONSIBILITY
-Co-Coordinator of the Immunopathology, Immuno-intervention and Transplantation, options of Master 2 BBRT Nantes (40h, 6 ECTS) (2013-present).

TEACHING AND TRAINING
-Master degree course at M2 Biology, Biotechnology and Therapeutical Research (BBRT), University of Nantes, Department of Sciences (2013-present) and at Master 1 Biological and Medical Sciences, University of Nantes, Department of Medicine (2015-present).
-Training of 6 phD candidates and of numerous Master and license students.
-Jury member of thesis defenses at the University of Toulouse (2016, 2020), Tours (2019), Poitiers (2019), Paris Sorbonne (2018), Lyon (2016) and Nantes (2014).
-Permanent jury at Master 2 BBRT at the University of Nantes (2013-present).

GRANT EVALUATION (2015-2020)
Fond de la Recherche Scientifique (Belgium) (2015-2020), PSL University of Paris Valorisation & Qlife (2020), Portuguese public funding agency for R&D (17 grants, 2021), UKRI Medical Research Council (2021), Wellcome Trust (2021)

Scientific summary

SCIENTIFIC EXPERTISE

Our team scientific activity is committed to basic and translational research and aim at better understanding the mechanisms of immune tolerance and the role of dendritic cells (DCs) in immunoregulation in order to identify new cellular and molecular therapeutic targets. Recently, the theme has then been expanded to the role of DCs and Mononuclear Phagocytes (MNP) in inflammatory diseases and in host-virus interactions in the context of transplantation and immunodepression.
We further developed new functional genomic approaches to better characterize MNP diversity and their role in immunopathology. Recently, we contributed to the understanding of the molecular basis of immunoregulatory MNP functions in transplantation (Cell Metabolism, 2019) anti-tumor immunity (Cancer Cell 2019, Blood adv. 2017, Front Immunol 2020) and inflammatory diseases (Mucosal Immunol, 2016; J Immunol, 2017; Cell 2019) as well Macs in lung infection (Nat Immunol 2020). We also demonstrated our ability to translate some of our findings to the clinic (The Lancet 2020).

SPECIFIC PROJECT : CLEC-1 in MNP and immunopathology (PI E Chiffoleau).

For the specific project, we previously identified CLEC-1, as being over-expressed in experimental model of allograft tolerance. CLEC-1 belongs to the "C-type lectin receptor" (CLR) family expressed mostly by myeloid cells and that recognize molecular patterns expressed by exogenous and endogenous threats, but also various proteins and lipids (e.g. DECTIN-1). Besides, CLR act as inhibitory or activating receptors to modulate myeloid cell activation, as well as magnitude and quality of downstream T cell response. We previously published that CLEC-1 is expressed in rat by immature myeloid cells and moderates the subsequent Th17 CD4+ T cell response (Thebault et al. J of Immunol 2009). The generation of rat CLEC-1 Fc fusion protein and CLEC-1 knockout rats (in collaboration with the TRIP platform, I Anegon) confirmed its role in DCs in the inhibition of effector Th1 and Th17 responses (Lopez-Robles Blood Adv. 2017). Furthermore, we demonstrated the expression of CLEC-1 on human dendritic cells and its role in the inhibition of subsequent Th responses . Our recent data suggest that CLEC-1 binds to DAMP(s) released by secondary necrotic cells and prevents the cross-presentation of dead cell-associated antigens to CD8+ T cells by conventional DC1. Consequently, CLEC-1 blockade enhanced anti-tumor responses in vivo and we observed a synergistic effect in combination with cytotoxic chemotherapy inducing CLEC-1 ligand release (patents EP 19306584.4 19306583.6). We now aim to study in depth the molecular mechanisms of the CLEC-1 checkpoint in mouse and human MNP in immunopathology by using functional genomics approaches. Particularly, we aim to identify the specific CLEC-1 ligand(s) and to decipher the role of CLEC-1 in MNP in subsequent T cell activation and anti-tumor responses by using experimental mouse models and scRNAseq approaches. Furthermore, in a translational program with the biotech OSEI, we aim to generate antihuman CLEC-1 mAbs to investigate CLEC-1 expression in human tumor MNPs and its role on MNP phagocytosis and cell activation. Funding: IHU-CESTI (2013-2016), Agence de la Biomédecine (2015-2016), Ligue (2017), Labex IGO 2018, CIFRE thesis (2016-2021), ANR PRCE (2019-2022), LIGUE (2021).