Sophie Ugolini
  • E-mail :[email]
  • Phone : +33 4 91 26 94 44
  • Location : Marseille, France
Last update 2017-01-12 12:44:17.928

Sophie Ugolini PhD Immunology, research director (DR2) INSERM

Course and current status

Current position

- Research Director (DR2), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille-Luminy (CIML),  France

- Member of the scientific advisory board of INSERM (2012-2017)

- Member of the scientific council of the office parlementaire d'évaluation des choix scientifiques et technologiques (OPECST)

 

Education

1998:                 PhD in Immunology, Aix-Marseille University, Marseille, France 

 

Research

1995-1998:        PhD work, laboratory of Quentin Sattentau, Centre d’immunologie de Marseille-Luminy (CIML), France.

1998-2000:        First postdoctoral position, Laboratory of Eric Vivier, CIML, France.  

2000-2001:        Second postdoctoral position, laboratory of Nicolas Glaichenhaus, Institut de Pharmacologie Moleculaire et Cellulaire (IPMC), Sophia Antipolis, Nice, France.

2001-2006:        Junior scientist (CR2, INSERM) in the NK Cells and Innate Immunity Laboratory, CIML, France.

2006:                 Visiting scientist, laboratory of Bruce Beutler, The Scripps Research Institute, La Jolla, California, USA.

2006:                 Senior scientist (CR1, INSERM), CIML, France.

2010-2015:        Co-management, with Eric Vivier, of the NK Cells and Innate Immunity Laboratory, CIML.

2012:                 Research Director (DR2, INSERM), CIML, France.

2013:                 Visiting Scientist, laboratory of Jean-Laurent Casanova, The Rockefeller University, New York, USA.

2015:                 Visiting Scientist at the Walter and Elisa Hall Institute (WEHI) and the Peter Doherty Institute for Infection and Immunity, Melboune, VIC, Australia.

2015-present:   Principal investigator of the ERC consolidator program “Neural Regulation of Immunity”, CIML, Marseille, France 

 

Teaching

1995-1998:        Cell biology tutor, Aix-Marseille University.

2002:                 Immunology teaching, Universités du Monde, Ougadougou, Burkina Faso. 

2005-2013:        Immunology teaching for Masters programs (M2), Aix-Marseille University

2007-2011:        Co-organizer of a Masters program (M1) at Marseille Medical School

2013:                 Co-organizer of a Masters program (M2), Aix-Marseille University

 

Committees and responsibilities

- Member of the scientific committee (# 1) of the Association pour la Recherche sur le Cancer (ARC), France (2009-2014)

- Expert for ANR (Agence Nationale de la Recherche)

- Expert for the FRS-FNRS (Fonds de la Recherche Scientifique), Belgium and for the Austrian Science Fund (FWF)

- Organization of internal seminars at CIML (2002-2015)

- Jury member for the Masters 2 course in Development and Immunology, Aix-Marseille University (2009-2010)

- Referee for Nature, Science Translational Medicine, Blood, PNAS, J. Immunol., FASEB J., Eur.J. Immunol, Int. Immunol., Scientific Report…

- Associate Editor, Frontiers in NK Cell Biology

- Editor, Immunology Letters

 

Selected grants (as a principal investigator)

- European Research Council (ERC) Consolidator grant (2015-2020)

- Fondation ARC (Programme ARC: 2014-2017)

- Agence Nationale de la Recherche (ANR programme blanc: 2014-2019)

- Projet exploratoire région PACA (2014-2016)

- Ligue Nationale contre le Cancer, SensorImmune (2014-2016)

- Agence Nationale de la Recherche (ANR Jeune Chercheur: 2007-2011)

- Agence Nationale de la Recherche (ANR-ERC starting grant: 2008-2012)

 

Prizes and Awards

1998:               Thesis award from Aix-Marseille University

2011:               Dandrimont-Bénicourt Award from the Institut de France

2012:               Prix Recherche de l’INSERM 2012 (Research award from INSERM)

2012-present: Prime d’excellence scientifique (Scientific excellence award, INSERM)

2013:               Prix Duquesne (Duquesne Award) from la Ligue Nationale contre le Cancer

2016:               Nomination AcademiaNet – Expert Database of Outstanding Female Academics 

 

Scientific summary

Past research achievements: Regulation of innate immune responses from single-molecule to systemic levels 

My principal research goal has been to understand how innate immune responses are regulated to establish potent anti-infectious and anti-tumoral functions without inducing excessive inflammation and auto-immunity. In particular, using natural killer (NK) cells as a model system in mice and humans, we have carried out genetic and functional studies to identify genes involved self-tolerance and immunity. Our lab is also involved in an ongoing clinical trial using NK cells as therapeutic agents in cancer patients (collaboration with Institut Paoli-Calmette, Marseille). our recent major scientific contributions include the following:

 

1. NK cell self-tolerance is ensured through the adaptation of their reactivity to the host molecular environment (Immunity 2006, PNAS 2009, Science Signaling 2011, Science 2012, Nature Com. 2014). NK cells use inhibitory receptors for self-MHC class I molecules to distinguish between normal cells and cells in distress. We demonstrated the presence of potentially autoreactive NK cells lacking inhibitory receptors for self-MHC class I molecules in human peripheral blood. Instead of inducing auto-immunity, these cells are hyporesponsive to various stimuli. We showed that interactions between inhibitory receptors and MHC class I molecules are involved in the calibration of NK cell effector capacities and in the acquisition of full functional competence (Anfossi et al., 2006; Sola et al., 2009). We used dynamic fluorescence correlation spectroscopy to study the underlying mechanisms and suggested that the confinement of activating receptors at the plasma membrane plays a key role in ensuring NK cell self-tolerance and responsiveness (Guia et al., 2011). We also identified the SHP-1 phosphatase as a major player in this process of immune tolerance (Viant et al., 2014). In parallel, we carried out ENU (N-ethyl-N-nitrosourea) mutagenesis in mice and identified a mutant with a loss-of-function mutation of the Ncr1 gene (encoding the activating receptor NKp46) that was highly resistant to viral infections, due to the presence of hyperresponsive NK cells. This study implicated the activating receptor NKp46 as a checkpoint in NK cell tuning (Narni-Mancinelli et al., 2012). Overall, these data indicated that NK cells adapted their reactivity to the host environment, through the engagement of activating and inhibitory receptors, revealing adaptive features of these innate immune cells.

 

2. NK cells cooperate with other immune cells to ensure efficient immune responses (PNAS, 2005, J. Exp. Med. 2012, Science 2012). Our early studies demonstrated cooperation between NK cells and macrophages in innate responses to pathogens (Baratin et al., 2005). We also showed that neutrophils were required for correct natural killer cell maturation, function, and homeostasis (Jaeger et al., 2012). In mice lacking neutrophils, we found that NK cells displayed hyperproliferation and poor survival and were blocked at an immature stage associated with hyporesponsiveness. The role of neutrophils as key regulators of NK cell functions was confirmed in patients with neutropenia. Thus, in addition to their direct antimicrobial activity, mature neutrophils are endowed with immunoregulatory functions that are conserved between mice and humans. We recently showed that NK cells were involved in the shaping of T-cell responses (Narni-Mancinelli et al., 2012) . We studied the immune response to viral and bacterial infections in mice harboring hyperresponsive NK cells (mutation of Ncr1) and we observed that the regulation of NK cell reactivity by NKp46 was critical for the subsequent development of T-cell responses.

 

3. Towards the development of clinical strategies for cancer treatment based on the enhancement of NK cell activation and survival (PNAS 2009, Blood 2014). A promising immunotherapeutic strategy targeting MHC class I+ cancer cells involves the use of monoclonal antibodies to block NK cell inhibitory receptors. However, as discussed above, interactions between MHC class I molecules and their inhibitory receptors are also required for the acquisition of NK cell functional competence and for self-tolerance in responsive NK cells. We developed a preclinical mouse model and showed, in vivo, that inhibitory receptor blockade with an antibody was safe, efficient and did not abolish NK cell responsiveness (Kohrt et al., 2014; Sola et al., 2009). Our results support the use of strategies based on inhibitory receptor blockade in cancer patients (clinical trials using anti-KIR and anti-NKG2A antibodies are already underway). We recently showed that BCL2 plays a major role in the survival and homeostasis of NK cells at steady state. We also showed that this anti-apopotic protein can be redundant when IL-15-dependent pathways are activated (Viant et al., 2017). Promising results have been obtained for the treatment of B-cell cancers (immunogenic to NK cells) with BCL2 inhibitors, and our data suggest that patients might benefit from combined treatment with IL-15 to increase NK cell survival and to promote anti-tumor responses. 

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