Grading

Once the visits for the 2012-2013 evaluation campaign had been completed, the chairpersons of the expert committees, who met per disciplinary group, proceeded to attribute a score to the research units in their group (and, when necessary, for these units' in-house teams). This score (A+, A, B, C) concerned each of the six criteria defined by the AERES. NN (not-scored) attached to a criteria indicate that this one was not applicable to the particular case of this research unit or this team. Criterion 1 -C1 : Scientific outputs and quality ; Criterion 2 -C2 : Academic reputation and appeal ; Criterion 3 -C3 : Interactions with the social, economic and cultural environment ; Criterion 4 -C4 : Organisation and life of the institution (or of the team) ; Criterion 5 -C5 : Involvement in training through research ; Criterion 6 -C6 : Strategy and five-year plan.

With respect to this score, the research unit concerned by this report (and, when necessary, its in-house teams) received the following grades:

 Introduction History and geographical location of the unit

This unit was previously located at Hôpital Henri Mondor in Creteil since 1996 (INSERM U448, U 659, UMR_S 841, creation and recreation under the same director, Mr A. BENSUSSAN). The current unit INSERM UMR-S 976 was created in 2009 at Hôpital Saint Louis, the historical Centre for Dermatology in France. Following an international call for applications from the host institution, Paris-St Louis Hospital/University Paris 7 Diderot, a new management was implemented combining research and clinical teams. Ms M. BAGOT, who was closely associated to the research unit since its creation at Hôpital Henri Mondor was appointed as Chair in charge of the merged clinical departments of Dermatology of the site and is acting as vice-director of the unit and co-team leader for team 1.

The new application (starting 2014), takes into account the request of the St Louis Hospital to include reconstructive surgery and regenerative medicine in association with dermatology and dermato-oncology, in parallel with the clinical activities located in the Hospital (plastic surgery, burn unit). The recruitment of a third team (Mr D. ABERDAM, epithelial stem cells, previously head of INSERM U898 in Nice) matches this goal. The founding unit has also recruited since 2009 a group to work on melanoma (leader team 2, Mr N. DUMAZ) besides cutaneous lymphoma, which was the core topic of the initial group.

As a consequence, the team has grown in size, and its proposed structure for the current evaluation includes 3 distinct teams.

•

Team 1 pathophysiology of cutaneous T cell lymphomas (CTCL) and cutaneous immunology

• Team 2 oncogenesis of melanoma

• Team 3 epithelial pathophysiology, stem cells and tissue repair.

Management team

The director (Mr A. BENSUSSAN) works in close collaboration with Ms M. BAGOT, who heads Saint-Louis Hospital Dermatology department and the French national cancer institute INCa's sponsored national reference centre for cutaneous lymphomas. They have implemented a management plan according to the Institution's ambitious roadmap (1) develop a centre of excellence for skin disorders and skin biology, including cutaneous oncology beyond lymphomas and chronic inflammatory skin disorders, (2) add regenerative medicine in the research theme to foster collaboration with the burn/reconstructive medicine department at St Louis Hospital, with (3) overall a strong emphasis on translational programmes and industrial collaborations.

INSERM has provided help with the recruitment of an administrative manager in the unit. • Influx of a new team with excellent credentials and of talented young scientists.

Unit workforce

• Generation of unique monoclonal antibodies with potential use in cancer immunotherapy.

• Good to excellent list of publications both for basic research and clinical research.

• Industrial valorisation (several patents, teams 1 and 2) and industrial partners.

• Very good funding profile (National institutes and Charities, EU, Industry).

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Strong local partnership with the Institute of Hematology (IUH) of Hospital Saint-Louis, a major international player in the field which should foster collaborations around lymphomas/leukemias, and gives access to research platforms.

• Implication and leadership (in top 5 at international level for CTCL according to visit committee) in national and international collaborative research (EORTC, Genomel, p63).

Weaknesses and threats

• Animal models: the visiting committee has specifically investigated this aspect which was acknowledged as a weakness by the team leader, because specific models are lacking for CTCL. For melanoma, patient-derived tumour xenografts are available and human-based alternative preclinical assays are implemented (histocultures, circulating tumour cells). The animal house facilities for mouse studies are of good standing. Team 3 has generated relevant mouse models transiently hosted at other institutions.

•

Interaction between teams around a major common theme are lacking. This aspect needs to be addressed in the five year plan.

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It has been noted that the number of academics working in CTCL is planned to decrease in the next 5 years raising questions about sufficient clinical backup available in the future for this field. Another weakness is the human resources in pathology for both human and animal studies. The vice-president of the host university has however informed the committee that this aspect of recruitment is a priority.

Recommendations

• Strengthen scientific interactions between the 3 teams: immunology of melanoma, cancer stem cells, reconstructed skin models are some possibilities for stronger interaction, but choices are difficult in very competitive areas and niches which combine added value of expertise of each team should be priorised.

•

Increase collaboration with the strongest local partner (Institute of Hematology), with obvious common research interests.

•

Besides scientists, plan balanced recruitment of pathologists and clinical researchers in accordance with major research fields, especially CTCL, immunodermatology, melanoma, regenerative medicine for adequate backing of research plans.

•

Put more emphasis on drug discovery and therapy especially for CTCL, chronic inflammatory skin disorders and regenerative medicine.

 Detailed assessments

Assessment of scientific quality and outputs

The 3 teams work on original projects and have made valuable progress in the field of CTCL, melanoma and stem cells over the last 5 year period. The unit members regularly publish in very good specialized and more general international journals.

Of note, in the 143 listed papers 2007-2012 for Teams 1-2

Assessment of the unit's academic reputation and appeal

As judged by the visiting committee, the overall reputation of the unit is rated good to excellent. Individual members are partners of international networks (EORTC, Genomel, Biogenomel, SkinDev). It is reflected by the status of associate editors in major specialty journal of several team members, numerous national and international scientific collaborations. The CTCL group is considered as top 5 at the international level. The organization of international congresses (13th International Congress of Immunology, Rio de Janeiro, 2007. 3 rd European Congress of Immunology, Glasgow), international speaking invitations, international missions of expertise (US, Israel, Italy), nomination at scientific governing committees (INSERM), and presidence of the French Society of Immunology (2007-9) underline the visibilty of the unit's leader and co-investigators.

The appeal is recognizable by the number of doctoral and postdotoral students trained during the last 5 years (16) the ongoing addition of a reputed team (Team 3) and the high standard of young scientists currently recruited by the unit.

Assessment of the unit's interaction with the social, economic and cultural environment

The unit director has been awarded two distinctions for the creation of a Biotechnology startup company (OREGA-Biotech) and interacts with several industrial partners (Innate Pharma, Galderma, l'Oréal, Johnson & Johnson…) with potential influence in the economic and health care.

The royalties from licensing to the industry of several monoclonal antibodies has produced royalties managed by INSERM (average 400 K€/year).

Both the unit leader and his academic co-investigators have been successful to disseminate their knowledge by participating to several academic programs and student training.

As witnessed by the committee auditions, the doctoral and postdoctoral trainees have been able to find positions in academic or industry jobs.

Assessment of the unit's organisation and life

The visiting committee has interviewed separately 3 groups of staff members: scientists, doctoral and postdoctoral trainees, and technical staff, and concludes that the unit is well organized.

The unit has easy access to biological materials from CTCL and melanoma patients due to a good organization from the clinic to the laboratory, situated at a short distance, and due to the presence of clinical trainees and staff resulting in good interaction for research goals. The research platforms of the site are easily accessible with good technical supervision.

Bimonthly lab meetings are organized for all the unit members. Laboratory council (Conseil de Laboratoire) is organized twice a year. Monthly meetings with the unit director of all the ITA staff are also organized.

Visiting scientists are coming on a regular basis and other scientific meetings are scheduled within the institution, but also in other places in the Paris area and all the unit members have an easy access to all the information, via websites, newsletters and billposting on the lab's noticeboard.

The committee has not found evidence of conflicts for access to financial support of team members. Overall, the recurrent institutional funding is around 25-30% of the unit's budget. The recurring institutional credit lines have been submitted to a substantial drop as in other French laboratories (159 to 105 K€ from 2010 to 2011) due to the change in structuration of French funding agencies but other sources have compensated the loss. Each team has been able to obtain good level funding, which is allocated according to unequivocal internal rules. The recurrent funding given by INSERM and Diderot University is used for purchasing consumables or equipment shared by all teams.

In addition, multiple patent licensing (royalties donated to INSERM around 400 KE/year) generates stable resources which can be allocated to specific needs.

Assessment of the unit's involvement in training through research

The visit committee concludes after site visit and discussion that the students are well supervised and guided. The unit belongs to doctoral schools (Ecoles Doctorales) Paris 7 and Paris 12. 12 doctoral students from Universities P7 and P12 have been trained during the past 5 years. All students have been granted scholarships.

For predoctoral students, 5 M1 students and 13 M2 students from several Paris Universities (P5 P7, P11, P12, P13, Ecole Pratique des Hautes Etudes) have been supervised during their bench training in the lab. A special attention is given to predoctoral training for M.D.s and to encourage the most motivated to enter a Ph.D. program. The director and co-director are involved in national and international training networks and education programs.

Assessment of the five-year plan and strategy

The creation of a skin research center in Saint Louis hospital to associate dermatology and plastic surgery in an ambitious project has been clearly stated by the host institutions. The proposed projects are a logical extension of previous research conducted individually by the 3 teams and tries to implement the roadmap defined in 2009.

This reinforced unit has good capacity for adaptation and several researchers either from Saint-Louis or Faculty of Medicine in Nice have joined or will join the unit in 2014 to fill the regenerative medicine/epithelial biology gap. All the unit members work on original projects in close relationship with the clinic and benefit from several available platforms at Saint Louis Hospital, especially from the major research partner Institut Universitaire d'Hématologie. As it is, the strategy is a good mix of basic and applied research including a wealth of academic and non-academic partnership.

As underlined above (recommendations) the recruitment of M.D. Ph.Ds is a priority for a balanced development of translational projects, and the strengthening of collaboration between teams around common goals cross nurturing expertise is strongly recommended. Over the last 5 years, Team 1 expertise has been consolidated in the field of CTCL, especially diagnostic biomarkers. It has identified KIR3DL2 (CD158k) as a biological marker for CTCL. Additional biomarkers, such as NKp46 and T-plastin, have also been discovered. Novel aspects are investigated concerning innate immunity related to the development of CTCL, via KIR receptor activation and a role for environmental triggers such as CpG DNA fragments interacting with TLR9. In collaboration with an italian team, team 1 showed that KIR3DL2 on NK cells is also a ligand for CpG-ODN and that after complex internalization CpG-ODN can encounter its ligand TLR9 in early endosomes. The work on CD 160 has produced an unexpected advance in angiogenesis. An anti-CD160 mAb, produced by the team in collaboration with Philippe LE BOUTEILLER, displays anti-angiogenic properties and corresponds to a promising candidate for cancer immunotherapy. Therapeutic developments using anti KIR Mabs are under investigation using in vitro and in vivo models. The development of 3D reconstructed models with the input of Team 3 may provide interesting insights into pathophysiology especially the role of innate immunity agonists.

The investigation of NF-kB signalling in CTCL and cutaneous inflammation driven by necroptosis is a novel promising axis, as well as the part on regulatory B cells, and altogether this part needs to be developped to foster interaction between groups implicated in chronic inflammatory disorders and those focusing on CTCL;

The scientific production is of good to excellent quality. Team 1 regularly publishes in specialized and more general international journals of high impact factor. best specialty journals in dermatology and immunology with members as first/last authors (5 J Invest Dermatol, 10 Blood, 7 J Immunol, 1 Immunity, 1 Immunol Rev). For high impact general scientific publications with members as first/last authors : 1 J Exp Med, 1 JCI, 2 PNAS and in collaboration 2 PNAS.

The ratio between the number of researchers and publications is balanced.

Patents (filed and licensed) illustrate the concern and competence of the unit for tranferring results to the industry. Competitive funding, both national and european, has been obtained.

Assessment of the unit's academic reputation and appeal

Researchers of team 1 have a strong and internationally recognized expertise in several aspects of cutaneous T cell lymphoma (CTCL) biology acknowledged by a solid publication record and involvement in national and international networks (EORTC, EuroTransbio). The CTCL group is considered as top 5 at the international level. The organization of international congresses (13th International Congress of Immunology, Rio de Janeiro, 2007. 3 rd European Congress of Immunology, Glasgow), international speaking invitations, international missions of expertise (US, Israel, Italy), nomination at scientific governing committees (INSERM), and presidence of the French Society of Immunology (2007-9) underline the visibilty of the unit's leader and co-investigators.

The appeal is recognizable by the number of doctoral and postdotoral students trained during the last 5 years (15).

Assessment of the unit's interaction with the social, economic and cultural environment

This part has been detailed above for the whole unit appreciation. To summarize, the team has solid partnerships with non-academic partners (Innate Pharma, L'Oréal…). with potential influence in the economic and health care. Team 1 director is a co-founder of a start-up in biotechnology (AREGA-BIOTECH in 2010). This team has produced several unique mAbs with promising transfer potential in to the clinic. Several biomarkers associated with CTCL have been patented and/or licensed and team has developed with Innate Pharma a diagnostic Kit for Sesary Syndrome based on anti-CD3, anti-CD4 and anti-KIR3DL2 labeling. Director and co-director regularly disseminate their knowledge by participating to scientific programs as well as student training, and have published reviews of their work in scientific journals.

Assessment of the unit's organisation and life

See previous comments on the whole unit, which apply here.

Assessment of the unit's involvement in training through research

See previous comments on the whole unit, which apply here.

Assessment of the five-year plan and strategy

The proposed goals have a clear translational scope, being based on the expertise of the team and, in general, on previous achievements that are well described. Presentation of the objectives is systematic and clear, including relevant unpublished information which contributes to justify their scientific interest and rationale. The intricate relationships between innate immunity, inflammation and initiation of lymphoma has not been sufficiently highlighted in the research plan and can be developed further given the expertise of the recruited scientists.

The previous comments on the whole unit for recruitment of clinician-scientists and pathologists applies to team 1

Conclusion  Strengths and opportunities

Team 1 has a long-standing and solid experience in the characterization of human leukocyte receptors, successfully oriented towards translational research in the diagnosis and therapy of CTCL with outstanding ability to transfer results to the industry. A diagnostic kit has been developed with Innate Pharma. It has the opportunity to develop immunotherapeutic strategies in CTCL by targeting KIR3DL2 such as by using chimeric mAb. Team 1 has also a very good experience with CD160 structure, expression regulation and functions.

The team has also a good experience with Treg cells, in particular CD39 + Treg, and their immunosuppressive function via production of adenosine. Targeting CD39 using an anti-CD39 mAb generated in the laboratory offers immunotherapeutic opportunities mainly in melanoma and HIV infection.

 Weaknesses and threats -CD160-GPI and NK/T lymphoma parts of the project are still exploratory and needs to be further developed.

-A preclinical CTCL mouse model is lacking.

-Team 1 has undertaken several collaborative studies on Treg, Breg, mast cells etc… in which it is much less competitive than in CTCL.

 Recommendations

Overall, the goals proposed for the next five years are satisfactory. Yet, the team together with the Dermatology Dpt., should eventually consider the opportunity to explore strategies aimed at progressively broadening the scope of their synergistic research in Immunodermatology to bridge innate immunity, inflammation, and CTCL initiation.

Stronger scientific interaction with the other teams, in particular team 2, should be developed in the five-year plan.

Given the needs for novel therapies in CTCL, give more priority to drug discovery and therapy, such as immunotherapy based on KIR3DL2.

Assessment of scientific quality and outputs

The team leader is a scientist (CNRS) with a strong expertise in the field of melanoma signaling. He will be assisted by two senior clinicians/researchers (PU/PH), with respectively expertise in melanoma clinical research/oncodermatology and dermatology oncogenetics. Team 2 has been emerging over the last 5 years and consists of ten researchers (scientists or academics), including seven from the former sub-group 'Oncogenesis of Melanoma' of the unit developing a project articulated around two major axes: signaling and genetics combined with a strong translational axis.

The signaling axis, directed by the team leader, has focused on the role of RAS/RAF/MEK/ERK (MAPK), PI3K/AKT and cAMP pathways in melanocyte transformation and melanoma proliferation and invasion. The aim has been to understand how these pathways are activated or inhibited in melanocytes and melanoma and how they interact to regulate melanoma growth. This study has led to the identification of new potential melanoma therapeutic targets (Kit, CRAF, PDE4).

Besides this fundamental work, a translational study has been conducted, in collaboration with the Department of Dermatology of the Institut Gustave Roussy, to understand the development of squamous cell carcinomas (SCC) associated with the use of Raf kinase inhibitor (Sorafenib) in the treatment of melanoma. The publication's record in relation with this work is very good: 6 articles in good to very good international journals (Small GTPase; Clin Cancer Res; Nature Structural and Molecular Biology, Oncogene, Plos One, Arch Immunol Ther Exp, mean IF=6,5) reporting original findings and 2 reviews. This work has also led to a patent, a licence agreement of a cell line with Sanofi-Aventis and a collaboration agreement with L'Oréal.

The melanoma genetics axis, more clinically oriented, is directed by one of the 2 senior scientists, Dermatologist and Professor of Genetics. The research has been mainly oriented on the study of genes involved in predisposition to skin cancers (basal cell carcinoma, melanoma) and genes involved in melanoma progression. This research has allowed to identify new genetic biomarkers in skin cancers (4 patents filed) as well as genetic factors involved in melanoma progression.

Since 2007, the scientific production of this axis has been good with 19 publications in Genetics and Dermatology journals reporting original findings (mean IF=4,2) and 2 reviews.

Along with these two axes, one the senior scientists (Head of Onco-Dermatology Department of Hôpital St Louis, Paris) has mainly conducted her research in collaboration within INSERM U940 where she contributed, through a translational study, to highlight the key role of the CD147/EMMPRIN molecule in the melanoma angiogenesis and lymphangiogenis. The number of publications of this senior scientist is impressive with more than 60 papers in the last 5 years as senior author or co-author, among which about 90% have an IF >4. Most of the publications arise from clinical activity, many of them are in prestigious (New Engl J Med (3), J Clin Oncol (2), Lancet Oncol) or very good (Plos Pathog, Clin Cancer Res, Blood, Clin Infect Dis, J Natl Cancer Inst…) journals.

Assessment of the unit's academic reputation and appeal

It seems premature to assess the academic reputation and appeal of this new team as a whole. However, the visiting commmittee has made observations regarding individual members.

The team leader was awarded (2011) a translational research contract with 'Assistance Publique-Hôpitaux de Paris' and has raised numerous funds from various national sources (Ligue Nationale Contre le Cancer, Société Française de Dermatologie, Fondation de France, INCA, PHRC), which is the marker of a national recognition. Besides, the team leader has an adequate visibility, as attested by invitations to meetings (mostly national), in the last ten years, by his activity as reviewer for AACR publications and for grants delivered by AICR (UK) and Ministry for Education University and Research of Italy.

Moreover, other researchers of the team are implicated in important national or international genomic and clinical research networks (Genomel, BioGenomel, Melancohort, INCA, PHRC). One of the senior scientist is recognized for his expertise in oncogenetics applied to dermatology at the National and European level, and has produced an important contribution to the diagnosis of xeroderma pigmentosum with the discovery of founder mutations for XPC and XPA in Maghreb families. The other senior scientist is recognized as a leader in melanoma and cutaneous oncology clinical research by her peers at the national and international level.

Assessment of the unit's interaction with the social, economic and cultural environment

The socio-economic output of the three PI together is good for a young team with filing of 4 patents (without licensing) and a licence agreement with an industrial group.

Assessment of the unit's organisation and life

It is also too early to evaluate adequately the management of the team. However, the team leader was able to organize a well-structured team, well-balanced in terms of the ratio of scientists/researchers whose skills and expertise in the biology and translational aspects of melanoma are complementary. Nevertheless, it should be noted, from the bibliographic analysis, that all the researchers of this team have had, in the past, little interactions with the team leader. There is a relative imbalance between the high number of senior researchers (scientists or clinicians) and the low number of junior ones. This should be corrected by the scheduled arrival of three postdocs in 2014.

Assessment of the unit's involvement in training through research

The involvement of the team members in educational activities is quite good due to the high number of professors (5). Moreover, most members of the team are involved in the training of pre-doctoral (master degrees) and Ph.D. students.

Assessment of the five-year plan and strategy

Based on published results and expertise, this new team proposes a bench-to-bedside research program centred on melanoma biology. Three major axes will be developped with a clearly-defined common objective to discover new targets for melanoma treatment and novel biomarkers for melanoma susceptibility.

The axis dedicated to the study of signal transduction addresses melanomas not yet eligible for new targeted therapies, namely Ras mutated, acral and mucosal melanomas. The goal is clearly defined and derives logically of the previous work of the team leader. The program of this axis is ambitious. The program of this axis being ambitious, the team could be strengthened to ensure a high level of competitiveness in the field.

The second axis, aimed at characterizing genetic biomarkers involved in melanoma susceptibility and progression, is a continuation of the past work of one of the senior scientist. Given the size of the group, the feasibility of the project is correct, especially since the researchers implicated have already in the past, collaborated and co-published together.

The third axis aims to identify, in melanoma microenvironment, novel therapeutic targets involved in tumour progression. In this context, the project focuses, on the one hand, on translational studies of two molecules, EMMPRIN and FERMT3, overexpressed in melanoma and known to induce MMPs expression and, on the other hand, on the role of kallikreins, a family of proteases. While the relevance of the various projects is very good and well-structured, the adequacy between manpower and real time implication for the clinicians to develop these projects is questionable, especially since these clinicians are also involved in an important pharmacology research project.

The whole project is fully relevant and of importance in the field. Nevertheless, the three axes are articulated in a series of 12 sub-topics, which, in view of the team's size, seems excessive to maintain a high competitiveness.

The access to clinical samples and to a preclinical platform are clearly added values.

Conclusion  Strengths and opportunities

The team has a good experience in translational cancer research leading to contribution in the discovery of new biomarkers. The group has been able to fund its research by grants obtained from competitive calls such as INCa and PHRC. The addition of the group of one of the senior scientist who is publishing at a high level and brings in the collaboration with a preclinical screening platform (pharmacogenomics) and access to large national cohorts and biobank (Melbase) as well as phase I trials is a major asset for this team.

 Weaknesses and threats

The number of post-docs and full time researchers involved in basic projects is too low in a very competitive field. Dispersal is a major risk for the competitivity of the team. It was not obvious at the visit that all sub-groups of this team fully benefit presently from the expertise each other but they seem keen to develop synergistic projects.

 Recommendations

It would be wise to clearly better define priorities in the project and to allocate adequate resources accordingly.

 Detailed assessments

Assessment of scientific quality and outputs

Knowledge of the mechanisms that control stem cell maintenance and activity during postnatal life is highly important for better understanding their role in organ regeneration and tumorigenesis. The research program of the team ("Epithelial Pathophysiology, Stem Cells and Tissue Repair") focuses on delineating the molecular mechanisms that control stem cell activity in the skin and other organs during development and postnatal regeneration.

The advantage of this highly successful program is a unique focus on the transcription factor-and microRNAregulated mechanisms that control stem cell activity in the developing and regenerating tissues. Following this route, the team has made several important discoveries that reveal an important role for micro-RNAs in fine-tuning the genetic programs regulating in adult stem cells by lineage-specific transcription factors.

The data generated by the team during the last five years (2008)(2009)(2010)(2011)(2012) are summarized in 21 original publications and reviews on different aspects of stem cell biology and tissue regeneration. It is important to note that this output was generated while the team was moving from Nice to Paris, with a strong interaction with Israel Institute of Technology, where the team leader has served as co-director of a stem cell lab under the auspices of INSERM and Technion. The 21 listed research papers are published in highly-ranked and prestige scientific journals, such as Proceedings of National Academy of Science USA (1), Mol Cell (1), J Cell Biol (1), Trends in Biochemical Sciences (1), Stem Cells (3), Cell Death and Differentiation (6), Journal of Investigative Dermatology (1), which is an important indicator of the high-quality research generated in this lab. General scientific publications with members as first/last authors.

Assessment of the unit's academic reputation and appeal

The team leader and his team have an undisputably high academic reputation in many different areas of biomedical sciences, such as developmental biology, stem cell biology, investigative dermatology,etc. The team is very productive and continuously generates high-quality data, which always receive positive feedback from the colleagues.

The strong academic reputation of the team is also evident from the fact that the team leader serves as a member of the Editorial Boards of several international journals including Stem Cells that publish a high-quality reports on the modern aspects of stem cell biology and tissue regeneration, and that he has been appointed since 2006 co-director a joint Israeli-French lab on stem cells located at the Israel Institute of Technology (Technion).

Assessment of the unit's interaction with the social, economic and cultural environment

The team actively interacts with social, economic and cultural environment via:

1. Communication with broad groups of researchers working in different areas of experimental biology and medicine throughout the project, demonstrating how complex approaches used for this study can lead to deeper understanding and progress of the research.

2. Publishing the results of this project in open-access high impact peer-reviewed journals and book chapters available for broad audience.

3. Engaging with the public audience directly through the institutions funded by the project and indirectly through the print, broadcast and online media to promote further understanding of developmental/stem cell biology and ageing in driving progress in these areas.

4. Communication with the pharmaceutical/cosmetic industry in exploring the application of different small molecules for modulation of skin regeneration and ageing.

5. The application to the rare disease p63 mutated ectodermal dysplasia group as a model is important for this group of patients and beyond for skin aging, bone development, and further dermocosmetics development in skin aging and hair biology. 6. Implication in ethical law on stem cells at French Senate and National hearings.

Assessment of the unit's organisation and life

The team consists of several sub-groups and includes 10 full-time research positions. The activity of members of the team is concentrated around five research projects focused on both fundamental and applied aspects of the molecular control of stem cell activity and tissue regeneration. Because of the appropriate combination of the experienced and young researchers working on different projects, the unit looks as very sustainable, capable of generating high-quality data and has a strong potential for further development. The addition of young investigators coming from plastic surgery and ophthalmology is expected to expand the applied research branch of the group and to develop translational projects locally in Saint-Louis Hospital.

Assessment of the unit's involvement in training through research

In Nice and Marseille, the team leader has been teaching on Stem Cells 2005-2012, and he has trained a team in Israel with the nomination of an assistant professor who is now taking the lead at Technion's stem cells lab.

Assessment of the five-year plan and strategy

The five-year plan presented by this unit consists of five distinct projects, which are closely linked to each other and also connected to the projects proposed by other groups (Team 2). The general focus of the five-year program is to delineate molecular mechanosms that control stem cell activity in epithelial tissues (skin, cornea) in normal and pathological conditions including EEC syndrome.

The major advantage of this program is a focus on integration on the transcription factor-and microRNAregulated mechanisms that control stem cell activity in the developing and regenerating tissues. The team will study the role of microRNAs in the modulation of the genetic program regulated by p63 trahscription factor in epithelial stem cells and their progenies (Project 1), as well will define a role of microRNA-184 in the control of keratin 15 expression in keratinocyte stem cells (Project 2). These two projects are closely linked to Project 3, which will further study the role of NFAT as one of the important regulators of stem cell activity. Project 4 will help to translate the results obtained in Projects 1-3 towards better understanding the role of epithelial stem cells and their progenies in the pathobiology of the ectodermal dysplasia EEC syndrome. Mr D. Aberdam's team will apply an iPS technology already established and extensively used in previous studies towards the correction of the EEC syndrome. Finally, the role of p63 and its target gene IGFBP-7 in the control of melanoma growth and progression will be studied in Project 5 as a part of collaboration with Team 2.

Overall, this five-year research program looks as very focused and balanced in terms of the combination of fundamental and applied aspects of the research, use of novel methods and approaches to understand biological roles of the transcription factor-and microRNA-mediated mechanisms of gene expression in epithelial stem cells and their progenies. All research methods and techniques required for execution of this program are available in the laboratory, which, together with high levels of expertise of the team members, suggest for a feasiblity of the proposed studies and high probability for the succes.

Conclusion

 Strengths and opportunities 1) The team leader and his team are highly regarded by the international scientific community in terms of the excellent productivity and strong academic reputation in developmental and stem cell biology.

2) Research unit has an appropriate combination of the experienced and young researchers working on different projects of stem cell biology and pathophysiology, which makes the team as very sustainable and having a strong potential for further development in the new environment, especially with surgeons of the burn and plastic surgery department.

3) Research plan is very focused and balanced in terms of the combination of fundamental and applied aspects of the research, use of novel methods and approaches to understand biological roles of the transcription factor-and microRNA-mediated mechanisms of gene expression in epithelial stem cells and their progenies.

4) All research methods and techniques required for execution of this program are available in the laboratory, which, together with high levels of expertise of the team members, suggest a good feasiblity of the proposed studies and high probability for success.

 Weaknesses and threats

The only minor weakness of the program is the availablity of the animal models for the research at Saint-Louis site. However, animals have already been bred at other facilities in Strasbourg and Orléans and should be available for research using new animal housing facilities in Paris to resolve this issue.

 Recommendations

To further support this highly productive team and their unique research program, which success will ultimatetely help to better understand mechanisms controlling stem cell activity in normal and pathological conditions and develop new approaches to modulate their functions for the needs of regenerative medicine and stem cell-based therapy. Strengthening links with other teams should result in higher impact outcomes for the whole unit.

2

  Assessment of the unit Strengths and opportunities • Balanced structuration for a main focus on Dermatology research including a multidisciplinary team (dermatologists, plastic surgeons, ophtalmologists, immunologists, cell and molecular biologists) with strong interaction between clinical and research groups. The close collaboration with clinical departments (dermatology, plastic surgery, ophthalmology) fosters existing and future translational research from discovery of novel phenotypic markers (e.g CTCL, melanoma), in vitro investigation of functional consequences, to drug development and clinical trials. • Recognised expertise of individual members and team leaders: CTCL, melanoma genetics, skin ESC and iPSC. • Existence of education tracks for M.D. Ph.Ds in Dermatology and Master degrees in Dermatology/ Democosmetics.

4

   Team-by-team analysis Team 1 : Pathophysiology of CTCL and Immunity Name of team leader: Mr Armand BENSUSSAN

  spent at least 12 months in the unit Number of Research Supervisor Qualifications (HDR) taken Qualified research supervisors (with an HDR) or similar positions  Detailed assessments

6

  Statistics by field: SVE on 10/06

Unit workforce Number as at 30/06/2012 Number as at 01/01/2014

				2014-2018
				Number of
				project producers
	N1: Permanent professors and similar positions	5 (1.4)	9 (2.6)	5
	N2: Permanent researchers from Institutions and similar positions	6	15 (13.6)	6
	N3: Other permanent staff (without research duties)	7 (6.6)	9 (8.6)	5
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)	1	1		1
	N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.)	5	4		5
	N6: Other contractual staff (without research duties)	2			1
	TOTAL N1 to N6	26 (22)	38 (29)	23
	Percentage of producers		100 %
	Unit workforce	Number as at 30/06/2012	Number as at 01/01/2014
	Doctoral students	4
	Theses defended	6
	Postdoctoral students having spent at least 12 months in the unit*	5
	Number of Research Supervisor Qualifications (HDR) taken	3
	Qualified research supervisors (with an HDR) or similar positions	12

,200 K€. Of

  note, DGOS-INca funding 500 K€, European grant Euro-Trans-Bio 200 K€. For 2007-12 11 patents obtained of which 5 patents licenced and 4 with ongoing licensing. For Team 3, 2 ANR and one INCa grants as coordinator, and partnership in PF7 Epistem, and Erare2 SkinDEv, plus industrial support.

	•	best specialty journals in dermatology and immunology with members as first/last authors (5 J Invest
		Dermatol, 10 Blood, 7 J Immunol, 1 Immunity, 1 Immunol Rev) and cancer 2 Oncogene, 2 Clin Cancer Res, 1 J
		Clin Oncol, 1 JNCI, 1 Lancet Oncol
	•	High impact general scientific publications with members as first/last authors : 1 Nat Struct Mol Biol, 1 J
		Exp Med and in collaboration 4 PNAS, 1 JCI
	•	Collaborative papers in the most prestigious medical journals : 3 N Engl J Med (melanoma trials, 1 JAMA
		(Kaposi HHV8)
		For the newcomer Team 3 of a list of 29 papers for the same period (corresponding to restructuration and
	moving from Nice to Paris with concomitant direction of Israel Institute of Technology stem cells lab)
	•	General scientific publications with members as first/last authors: 1 PNAS, 6 Cell Death Differ, 3 Stem Cells
	•	Collaborative papers 1 Mol Cell, 1 PNAS, 1 J Cell Biol, 1 J Invest Derm
		For Teams 1-2 major grants have been obtained at National (ANR, INCa, PHRC) and European levels, plus
	industrial contracts, totalizing more than 3

Armand BENSUSSAN


INTRODUCTION HISTORY AND GEOGRAPHICAL LOCATION OF THE UNIT

The unit was created in 2014 with Ms Veronique Baud as director. Originally located at the Institut Cochin it relocated to the Faculté de Pharmacie de Paris in December 2016.

MANAGEMENT TEAM

Unit head is Ms Veronique Baud and deputy head is Mr Thierry Molina.

HCERES NOMENCLATURE

SVE5

SCIENTIFIC DOMAIN

The focus of the unit is the molecular characterisation and treatment of B-cell haematopoietic malignancies, with particular emphasis on the role of the RelB NF-kappaB subunit.

UNIT WORKFORCE

GLOBAL ASSESSMENT OF THE UNIT

The focus of the 'NF-kappaB, Différenciation et Cancer' based in the Faculté de Pharmacie de Paris at the Universite Paris Descartes is the role of the RelB NF-kappaB subunit in B-cell malignancies. Since the previous evaluation report, the unit has made significant progress in this area. The future projects data have the potential to have a significant impact both in our understanding of the role of NF-kappaB in cancer but, importantly, in the treatment of patients with this disease. The strong links between the basic and clinical research are particularly noteworthy. The unit has been very productive both scientifically and clinically. There is good synergy between the basic research and clinical activities that has led to important scientific discoveries of direct relevance to the treatment of patients with B-cell malignancies. This is reflected in the high number of scientific and clinical articles and book chapters. The research being performed is novel and of an international standard, leading to publications in leading journals in the field. Furthermore, the unit is actively engaged in translating these finding into the clinic, both through the ability to access patient material and leading clinical trials. The unit has been successful in attracting European and National funding. Members of the unit are active participants in the scientific community. This is reflected by membership of editorial boards, acting as manuscript reviewers and participation in other peer review activities. In addition, members of the unit are invited to speak at scientific symposia. The unit is therefore very actively engaged at all levels of scientific and clinical work.

During this period the unit successfully relocated from the Institut Cochin to the Faculté de Pharmacie de Paris in December 2016, where it has now established a productive and thriving work environment. Overall the unit is performing basic and clinical research to a high, international standard.

The evaluation reports of Hceres are available online: www.hceres.com

Evaluation of clusters of higher education and research institutions Evaluation of higher education and research institutions Evaluation of research Evaluation of doctoral schools Evaluation of programmes International evaluation and accreditation


Grading

Once the visits for the 2012-2013 evaluation campaign had been completed, the chairpersons of the expert committees, who met per disciplinary group, proceeded to attribute a score to the research units in their group (and, when necessary, for these units' in-house teams). This score (A+, A, B, C) concerned each of the six criteria defined by the AERES. NN (not-scored) attached to a criteria indicate that this one was not applicable to the particular case of this research unit or this team. Criterion 1 -C1 : Scientific outputs and quality ; Criterion 2 -C2 : Academic reputation and appeal ; Criterion 3 -C3 : Interactions with the social, economic and cultural environment ; Criterion 4 -C4 : Organisation and life of the institution (or of the team) ; Criterion 5 -C5 : Involvement in training through research ; Criterion 6 -C6 : Strategy and five-year plan.

With respect to this score, the research unit concerned by this report (and, when necessary, its in-house teams) received the following grades:

 Grading table of the unit: NF-kappa B, Differentiation and Cancer

C1 C2 C3 C4 C5 C6 A A A A B A 1  Introduction
History and geographical location of the unit:

Ms Véronique BAUD joined Institut Cochin in 2004 upon return from a post-doctoral period in San Diego USA. After 3 years as a member of a team, she obtained an independent status as team leader of a "Groupe Cochin" in October 2007. The team, which has recently associated with a group of clinicians, one of whom is a co-PI of the present project (Mr Thierry MOLINA) will now move to the Faculty of Pharmaceutical Sciences of the Paris 5 University to develop a project centered on the alternative pathway of NF-κB signalling in B lymphoid malignancies.

Management team:

During the period under evaluation (2007)(2008)(2009)(2010)(2011)(2012) the team increased in size from 1 permanent scientist (VB), one technical support and 1 PhD student to 7 members in 2012 (2 permanent scientists, 2 clinicians, 1 permanent CNRS engineer, 1 post-doc and 1 PhD student). 2 PhD theses were defended (2007 and 2012) and 7 master students were trained in the lab (3-4 months rotations). One PhD thesis is ongoing (2011-).

Ms Véronique BAUD and Mr Thierry MOLINA are candidates for an EA research unit at University Paris Descartes and an ERL CNRS label.

AERES nomenclature:

SVE1-LS4

Unit workforce: (1) The area of research is very interesting. Although NF-kB has been studied for more than 25 years, the focus in recent years has been on the upstream signaling components, and in particular the processes leading to activation of the IKK complex in the 'classical' pathway. The study of the function of the subunits and RelB in particular of the non canonical NF-kB pathway, has consequently been neglected. In particular, the advent of many powerful new technologies has, in general, not been fully exploited to investigate the function of these proteins. Given our increasing understanding of the role of NF-kB in cancer, and a growing appreciation of the role of the 'alternative' NF-kB pathway, a consequence of this is that the work proposed by the Baud/Molina group is both timely and exciting. Specific strengths include:

•

An exciting research program ;

• The solid previous track record of the two PIs ;

• Good visibility and contacts (national and international) ;

• Many collaborations (although this could also be a threat -see below) ;

•

The capacity to ensure adequate funding through ANR BiotecS (2012BiotecS ( -2015)), INCa Lymphoma Network.

(2) The proposed projects are based on a significant amount of solid recent data, much of which has been published. The outlined programme of work is a good balance between follow up studies based on these data combined with further 'discovery' elements such as proteomics and transcriptomics.

(3) The involvement of Mr Thierry MOLINA will help the team translate their work from the laboratory to a clinical setting, which will increase the overall impact of their research.

Weaknesses and threats:

(1) It is unclear whether the new environment at the Faculté des Sciences Pharmaceutiques et Biologiques will be optimal for the group. Although there is potential for collaborations with established groups with expertise in the synthesis of pharmacological inhibitors or crystallography/NMR, no clear and concrete contacts have been established yet. Furthermore, while the team has established outside collaborations to analyze proteomics, transcriptomics and ChiP-Seq data, it is not clear if such expertise, in particular bioinformatics, exists at the new location of the group. Although these approaches can be outsourced to collaborators in the longer term it is often more efficient to be able to perform these on site.

(2) Five subprojects are planned with somewhat limited workpower: 1.5 to 3/4 full time equivalent each. There is therefore a recognized need for recruitment of additional research staff in a near future. Before this happens, it is difficult to imagine that all projects can be carried out at an internationally competitive level.

(3) It is not clear if one engineer from CNRS, already in the group since 2005, will be allowed, for administrative reasons, to follow the team.

(4) The level of international competition is high (446 references in the web of science for RelB in the last 10 years, 430 for NF-κB and leukemia or lymphoma, 100 for RelB leukemia/lymphoma).

Recommendations:

Given the size of the team, more focus is recommended with clear prioritization of the different projects.

To facilitate the completion of the ambitious research programme, the plan to recruit a young and highly motivated researcher for a permanent position should also be a priority.

Emphasis should be placed on ensuring good integration of the group with other researchers at the new campus. Also, it is very important that this small team improves its attractiveness towards students. The projects would benefit a lot from the recruitment of more post-docs and PhD students.

The committee recommends caution about the team's involvement in too many projects that could be considered opportunistic as opposed to the well-focused research presented in the report. Although leading to coauthorship of many papers, outside collaborative projects may distract from the core efforts constituting the lab's main project.

 Detailed assessments

Assessment of scientific quality and outputs:

The group is internationaly recognized in the field of NF-kB and has published some highly original work establishing the concept of RelB as a tumor suppressor in p53 wt tumors (Oncogene, J. Biol. Chem.). The Oncogene paper in 2012 will likely be highly cited. The work will make a significant contribution to the field by shedding light on the alternative pathway of NFkB in B cell lymphoma development. The group has identified new regulatory components of the IKKa complex that may define an original signaling complex for DNA damage. Thus, although the overall output in terms of the number of publications from the team's own projects (i.e. outside of collaborations in which no team member is a senior author) is not very high, the work is of good to very good quality.

Assessment of the unit's academic reputation and appeal:

This is exemplified by invitations to speak at international conferences ( VB: Keystone, 2 international workshops on NF-kB; TM: 2 European Hematology workshops). Moreover, there are established networks with industry (ANR) and clinics (NFkB and lymphoma). There is recognised expertise in NF-kB signalling. However, although the group has grown in size during the period of evaluation, its attractivness to students and young researchers is still insufficient.

Assessment of the unit's interaction with the social, economic and cultural environment:

The team has established industrial contracts with the clear potential for development of inhibitors of the pathway.

There is evidence for some cultural activity (1 meeting organization) but there is necessity to improve in this area in the future.

Assessment of the unit's organisation and life:

Due to the small size of the team there was no real need for development of the particular management skills associated with larger organisations and so the committee did not feel it was possible to score this section. However It was noted that although there is evidence of a good "esprit de corps" among the research group, there are concerns about the day to day management of the team, such as an over-reliance on the technical expertise of one engineer, where in the longer term training of all lab members might be beneficial. The committee of experts recommends the PIs evaluate the best way to manage this group to maximise scientific output.

Assessment of the unit's involvement in training through research:

Despite only one HDR at the beginning of the project, four M2, one M1 students, two PhDs were trained.

There is limited participation in teaching activities.

The committee noted that there appears to be limited attractiveness for foreign students (1 italian Master 2 student).

Assessment of the five-year plan and strategy:

The project is based on solid and published results from the group, with intelligent and ambitious goals. If it succeeds it will make a significant contribution to the field of NF-kB research. The group shares good collaborations with several researchers in the field.

However, the committee had some concerns. Although several people have been recruited to the project, there was concern about the overall feasibility, as the group is pursuing too many questions with limited human resources. Therefore, there could be a gap between the level of scientific ambition and the feasibility of the project. In addition to the number of lab members, there is also a concern about the overall level of funding and resources available to the group, which will limit the scope of their research. It may be necessary for the group to focus on specific, key goals of the project (such as the novel function and members of the IKKa complex).

The committee did note that one high level young researcher is planned for recruitment (Inserm/CNRS) and agreed that this would strengthen the team.

There was also concern about the immediate environment. The committee did not succeed in getting sufficient information concerning the new scientific environment as well as clear details about lab space.

The committee appreciated the strong support by the Dean of the Faculty to get the team as a first step towards an UMR application in the next 4/5 years.

 Conduct of the visit

Conduct or programme of visit:

The visit had been carefully prepared and members of the committee liked the scientific quality of the oral presentation. We thank the Aeres visiting committee for the fair assessment of our research unit and constructive remarks. Nonetheless, we would like to answer to the three main points highlighted by the committee:

1-Reasons for selecting the new host Institute

The visiting committee was eager to have some more information regarding our new environment at the Faculté des Sciences Pharmaceutiques et Biologiques.

First, we are pleased that the committee has appreciated the "strong support by the Dean of the Faculty to get the team as a first step towards an UMR application in the next 4/5 years".

Second, we would like to reassure the visiting committee that by selecting the Faculté des Sciences Pharmaceutiques et Biologiques as part of the Université Paris Descartes, we will benefit out from an outstanding multidisciplinary working environment giving the opportunity to exchange idea with many scientists and benefit out of their expertise in various domains including novel anticancer therapeutics, signal transduction and biochemistry.

Third, it is important to note that since the visit of the Aeres committee on February, 19 th , 2013, the Faculté des Sciences Pharmaceutiques et Biologiques was declared priority as part of the "plan campus" and was awarded a 50 M€ grant for its renovation, thus laying the foundations for a novel successful Research Center as part of the University Paris Descartes. Thus, there is no doubt that we will benefit out the required fully renovated lab space at the time of our arrival, and work in a very efficient and competitive environment.

Finally, regarding the core facilities, it is the political choice of the University Paris Descartes to have a network of core facilities located on different sites within Paris (e.g. Faculté des Sciences Pharmaceutiques et Biologiques, Institut Cochin, Necker). Thus, beyond the ones provided at the Faculté des Sciences Pharmaceutiques et Biologiques Pharmacie (e.g. animal facilities, cellular imaging, microscopy), we will get full access, when required, to the core facilities available at the Institut Cochin (located at walking distance), and at Necker (15 min by bus). It is particularly well illustrated for bioinformatics ("while the team has established outside collaborations to analyze proteomics, transcriptomics and ChIP-Seq data, it is not clear if such expertise, in particular bioinformatics, exists at the new location of the group"), since we have already started to work in close contacts with Jean-Philippe Jais and Nicolas Cagnard at Necker for in-depth bioinformatics and biostatistics analysis.

2-Reinforcement of the team and prioritization of the different axis of the research project in regards to the size of the team "To facilitate the completion of the ambitious research program, the plan to recruit a young and highly motivated researcher for a permanent position should be a priority"

We are aware that our team would benefit from reinforcement by young permanent position scientists. We are pleased that the committee highlighted that "one high level young researcher is planned for recruitment and agreed that this would strengthen the team", namely Emmanuel Derudder, a former PhD student in the group who is currently a post-doctoral fellow in Klaus Rajewsky lab (Max Delbrück Center for Molecular Medicine, Berlin, Germany) and would like to join us provided that he will be recruited by an EPST (CNRS-INSERM). He is an expert in Immunology and IKK/NF-κB conditional knockout mouse (Baud & Derudder, Curr Top Microbiol Immunol, 2011;Derudder et al., Nat Immunol, 2009;Sasaki, Calado, Derudder et al., PNAS, 2008;Sasaki, Derudder, et al., Immunity, 2006).

"it is not clear if one engineer from CNRS, already in the group since 2005, will be allowed, for administrative reasons, to follow the team" Indeed, the transfer of Didier Bordereaux, our excellent CNRS senior research assistant (IE1), to our novel structure crucial might be a tricky issue. Nonetheless, he is deeply determined to keep working with us. Thus, we have good hope that, with the help of the CNRS i.e. the ERL CNRS label, we will keep working side by side for the years to come.

"Given the size of the team, more focus is recommended with clear prioritization of the different projects"

We agree with the committee and are fully aware that, in regards to the current size of our team, we have to focus on specific key goals of the project for an optimal development at an internationally competitive level. It is exactly the reason why, for the past months, we have given priority to the identification of new IKKα/RelB interacting partners and their functional characterization. It has led to three articles (JBC, 2011, Oncogene, 2012 + one article submitted), and still is the main topic of our ongoing research.

The committee recommends caution about the team's involvement in too many projects that could be considered opportunistic as opposed to the well-focused research project presented in the report. Although leading to co-authorship of many papers, outside collaborative projects may distract from the core efforts constituting the lab's main project

As experts in the field of IKK/NF-κB, we are often contacted to collaborate to scientific projects that required the evaluation of the IKK/NF-κB activation status. We would like to reassure the committee that we are cautious to only accept collaborations in regards to their scientific excellence and most complementary expertise. It is highlighted by top-level peer-reviewed collaborative publications (Nature Medicine, EMBO J, Blood,…).

3-Improvement of attractiveness towards students

"The team will benefit out from the recruitment of more post-docs and PhD students"

First of all, we are pleased that the visiting committee pointed that despite only one HDR (V. Baud), during the period of evaluation (2007)(2008)(2009)(2010)(2011)(2012), five M2, one M1, two PhDs and 4 Post-Docs were trained. The recent reinforcement of the team by two new members with permanent position and HDR (Thierry Molina & Corinne Besnard-Guerin) as well as our new very attractive scientific environment, will without a doubt allow us to recruit more Post-Docs and PhD students.

Finally, although the committee noted that there appears to be limited attractiveness for foreign students (1 italian Master 2 student), we would like to point out that during the period of evaluation we also have welcomed 1 Peruvian Master 2 student (Hugo Valencia) and 1 Albanian Master 2 student (Aleksandra Spiro).

Sincerely yours, Véronique Baud Thierry Molina

  . street town):24, rue du Faubourg Saint Jacques, Paris

  8h30 -9h00: Closed door session: committee and AERES Scientific advisor 9h00 -9h15: AERES representative: the role and procedures of AERES : presence of all the team's members 9h15-10h15: Director of the Unit: Presentation of past activities and future projects 10H15-11H00: Discussion with the representatives of the managing bodies 11H00-11H30: Coffee break 11h 30-12h15: meetings with personnel (without direction and managing bodies) Discussions with engineers, technicians, administrative Discussions with staff scientists Discussions with students and post-docs 12h15-13h30: Lunch 13h30-17h: -Discussion with head of the unit -Private meeting of the visiting committee and AERES Scientific advisor 17h00: End of the visit 5  Statistiques par domaine : SVE au 10/06

Unit workforce Number as at 30/06/2012 Number as at 01/01/2014

				2014-2018
				Number of
				project
				producers
	N1: Permanent professors and similar positions	1 (40)	1 (40)	1
	N2: Permanent researchers from Institutions and similar positions	2 (200)	3 (300)	2
	N3: Other permanent staff (without research duties)	2 (130)	4 (170)	1
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)
	N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.)	1 (100)	1 (100)	1
	N6: Other contractual staff
	(without research duties)
	TOTAL N1 to N6	6	9	5
	Percentage of producers		100 %

Unit workforce Number as at 30/06/2012 Number as at 01/01/2014

	Doctoral students Theses defended Postdoctoral students having spent at least 12 months in the unit* Number of Research Supervisor Qualifications (HDR) taken Qualified research supervisors (with an HDR) or similar positions 2

 Assessment of the unit Strengths and opportunities:

EA University Paris Descartes and ERL CNRS label Director's comments on the Aeres report on unit "NF-kappaB, Differentiation and Cancer"

		Unit name: NF-κB, Differentiation and Cancer
	A+	67 Project Leader: Véronique Baud & Thierry Molina 62 52	73	65	60
	A		57	67	71	45	65	63
	B		12	7	4	7	6	14
			Label requested:
	C		0	0	0	3	0	1
	Non Noté	3	3	12	11	3	1
	Pourcentages
	Critères	C1 Qualité scientifique et production	C2 Rayonnement et attractivité académiques	C3 Relations avec l'environnement social, économique et culturel	C4 Organisation et vie de l'entité	C5 Implication dans la formation par la recherche	C6 Stratégie et projet à cinq ans
	A+		48%	45%	37%	53%	47%	43%
	A		41%	48%	51%	32%	47%	45%
	B		9%	5%	3%	5%	4%	10%
	C		0%	0%	0%	2%	0%	1%
	Non Noté	2%	2%	9%	8%	2%	1%


President Michel Cosnard

Paolo Madeddu

This report is the sole result of the unit's evaluation by the expert committee, the composition of which is specified below. The assessments contained herein are the expression of an independent and collegial reviewing by the committee.

UNIT PRESENTATION

INTRODUCTION HISTORY AND GEOGRAPHICAL LOCATION OF THE UNIT

The unit currently is located at the Georges-Pompidou European Hospital. The site provides 4200m 2 space with laboratories, offices and core facilities, hosting a multi-disciplinary team of more than 250 basic, translational, and clinical scientists, as well as trainees, administrative staff and technicians. The unit has a long history of excellence and leadership in cardiovascular medicine and exerts strong influence on the international scientific society. In the last 5 years, the unit has strengthened its clinical focus with merging of new personnel in strategic sectors of their portfolio.

MANAGEMENT TEAM

Ms Chantal Boulanger has been selected by the team leaders as the new director of the unit. She will overlap with Mr Alain Tedgui in leading the unit during the next 12 months and then take full responsibility.

HCERES NOMENCLATURE

GLOBAL ASSESSMENT OF THE UNIT

The unit has developed an outstanding program in the field of cardiovascular medicine, accomplishing exceptional results in the identification of molecular and cellular mechanisms implicated in the pathogenesis of atherosclerosis, heart attack and peripheral ischemia. They conducted epidemiologic and genetic studies in large groups of patients, which led to the identification of biomarkers and determinants of cardiovascular diseases. Moreover, they performed interventional studies for the assessment of safety and efficacy of novel treatments. Qualitative and quantitative indicators support the success of the activities developed during the last years. All the components of the unit have an internationally competitive publication record, with an exceptional number of publications and great influence on the scientific community. Unit members chaired international meetings and contributed substantially to editorial and reviewer activity of major journals and grant committees. The unit has an excellent training program and is well connected to society, with a number of initiatives to communicate results and the impact of their research on patients' lives. Unit members have succeeded in translating basic research into the clinic and conducted world class epidemiological and therapeutic clinical trials.

The evaluation reports of Hceres are available online : www.hceres.com

Evaluation of clusters of higher education and research institutions Evaluation of higher education and research institutions Evaluation of research Evaluation of doctoral schools Evaluation of programmes International evaluation and accreditation

Hcéres scientific officer:

Ms Florence PINET

Representatives of supervising institutions and bodies:

Mr Raymond BAZIN, Inserm Ms Marie-Pascale MARTEL, Inserm Mr Stefano MARULLO, Université Paris-Descartes