Evaluation report

This report is the sole result of 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. The EA 3181, entitled "Epithelial Carcinogenesis: Predictive and Prognostic factors" was created in 1996. It is located at the faculty of medicine and pharmacy at the university of Franche-Comté in Besançon. The research group works on both fundamental and clinical aspects of cancer, working to understand the mechanisms leading to the development of epithelial cancers that may or may not be associated with Human Papilloma Viruses (HPV). A wide variety of different research topics have been investigated from molecular biomarkers of virus-induced tumors to cancer patient quality of life. Other objectives are to propose innovative approaches to primary and secondary prevention and therapeutic management, and to evaluate the impact of new treatments on the quality of life of patients with cancer. To be able to manage this variety of scientific interests, the research unit has developed an impressive number of national and international collaborations, which were concretized by numerous co-authorship publications

Management team

The unit is under the direction of Ms Christiane MOUGIN. As of the beginning of 2017, she will be succeeded by Mr Jean-Luc PRETET. Over the last period, the team has been very productive, listing >300 international publications often published in top-ranked journals. There are noteworthy contributions in a variety of fields, such as HPV in skin cancer, mechanisms of HPV-induced carcinogenesis in anogenital cancers as well as a prominent clinical research portfolio on several epithelial cancers, performing large clinical trials with noteworthy results on improved treatment and studies on quality of life. The HPV-associated work has progressed well and follows the development of the field. The proposed strategy is to focus on this line of research for the future.

Global assessment of the unit

The unit is characterized by a large output of careful and solid work in several areas of cancer research on epithelial tumors. Their past and future main topic is cancer associated with HPV infection. Their research is patientdriven with access to patient samples or epidemiological data and participation to clinical trials. The research unit has national and international recognition. Although the team has undoubtedly been interdisciplinary, synergistic effects are not so clear and a focusing of the efforts may be required. The proposed strategy to focus more on HPVrelated work is encouraged.

Strengths and opportunities in the context

Major strengths include a productive track record of careful and solid research (from the last evaluation: 289 papers were published of which 78% are cancer-related, the first and last author IF median is nearly 3), an effective interdisciplinarity and an international and national network of collaborations. There is also a strong track record in research training.

Weaknesses and threats in the context

Although the unit is productive in terms of number and quality of publications, it is more difficult to clearly pinpoint what the five major findings really are. Research is performed in too many areas that are not obviously interlinked (the interactions and the coordination between the 13 scientists associated to the unit is not clear). The internationalization could be even more strengthened, for example by recruiting international post-docs and students. The number of national and international grants is small. The committee is concerned that the team may be stretching itself too thin. The more focused effort that the unit proposes for the next five years could have a strong impact.

Recommendations

The team will most likely benefit from the proposed focusing further on a single subject of research (HPV and HPV-associated cancers). These could be approached using a variety of interdisciplinary approaches (basic science on molecular mechanisms, immunotherapy, clinical and epidemiological studies, etc.). The interest in biomarker studies and their clinical and epidemiological validation could be developed further. The publication strategy should be more focused on a smaller number of higher impact publications in the same line of research. Although international collaborations and collaborations with industry are described and are interesting, the funding is limited and the team could benefit from focusing only on well-funded projects. Leading clinical investigators and the well-known director will be leaving, and the new director will have a challenging task to ensure smooth continuation and continued improvement.

  Ms Nathalie JACOBS, University of Liege, Belgium Scientific delegate representing the HCERES: Mr Jean ROSENBAUM Representative of supervising institutions and bodies: Mr Lamine BOUBAKAR, Université de Franche-Comté Head of Doctoral School: Mr Patrick PLESIAT, Doctoral School n°554, "Environnements-Santé" 1  Introduction History and geographical location of the unit

N3:N4:N5:

  santé publique, recherche clinique, technologies biomédicales SVE1_LS6 Immunologie, microbiologie, virologie, parasitologie Scientific domains Molecular mechanisms of cancer. Viral infections as causes of cancer. Immunotherapy of cancer. Cancer prevention and epidemiology. Permanent researchers from Institutions and similar positions 5 5 Other permanent staff (technicians and administrative personnel) 4 5 Other professors (Emeritus Professor, on-contract Professor, etc.) 2 Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.) N6: Other contractual staff (technicians and administrative personnel) spent at least 12 months in the unit Number of Research Supervisor Qualifications (HDR) obtained during the period 1 2  Overall assessment of the unit Introduction


Christiane Mrs

Mougin

M Juergen Siepmann

M Thomas

M Laurent Dubuquoy

M Michel Plotkine

M Stéphane Rocchi

M David

M Jacques Bahi

The visit took place on 2nd March 2011 and included presentations of the director of the research unit as well as of some of her collaborators. The presentations were followed by discussions with the review committee. In addition, separate discussions were held with the review committee members and the following three groups of personal: (i) PhD students and postdoctoral fellows, (ii) engineers, technicians and administrative assistants, and (iii) researchers with permanent position, all in the absence of the director of the research group. Furthermore, posters were presented and allowed for an exchange between the review committee members and team members. The review committee also met the vice-president for research of the University of Franche-Comté as well as other representatives of the Faculty of Medicine and Pharmacy, University and University hospital.

 History and geographical localization of the research unit, and brief presentation of its field and scientific activities

The EA 3181, entitled "Epithelial Carcinogenesis: Predictive and prognostic factors" was created in 1996. It is located at the Faculty of Medicine and Pharmacy at the University of Franche-Comté in Besancon. The research group works on the fundamental and clinical aspects of cancer treatment. In particular, the team focuses on the following two types of cancerogenesis: (1) human papillomavirus (HPV)-associated cancerogenesis, with the following sub-topics: understanding the role of anti-TNF (anti-Tumor necrosis factor) in resistance to apoptosis, understanding the mechanism of horizontal transfer of viral oncogenes, expression of HPV genes and their regulation by epigenetic mechanisms, (2) urothelial carcinogenesis, with the following sub-topics: identification of molecular markers, understanding the role of PPAR (Peroxisome Proliferator-Activated Receptor) in regulating the expression of these markers, understanding the mechanisms by which PPARgamma ligands act.

 Management team:

The management team is limited to the director of the group. 2  Overall appreciation on the research unit

 Staff members

 Summary

The clinical research of the group is very strong, with a considerable number of publications in journals with very high impact factors. The entire team covers the whole range from fundamental to clinical research and is well managed. The director of the group is an opinion leader in the field of human papillomavirus (HPV)-associated cancer, several other members are also very well visible at the international level. The group considerably contributes to European organizations, such as the EORTC (European Organisation for Research and Treatment of Cancer) and is actively involved in the organization of national and international scientific meetings. The impact of the research is very significant with respect to the clinical treatment of cancer and addresses a field of great interest for the public health. The quality/originality of the fundamental research of group should be improved in the future, including more risk-driven, cutting edge projects. The publication activity of this relatively small group in the field of clinical research is remarkable. This includes articles in general journals with very high impact factors. The group actively collaborates with the University hospital and industrial/academic partners on the local, national and international level.

 Strengths and opportunities -The research unit covers the whole range from fundamental research to clinical research. Thus, it allows the transfer of new findings in more basic biological/medical science into practical applications for the patient.

-The director of the research group manages this highly interdisciplinary team very efficiently.

-The clinical research of the group is very strong.

-The director of the research unit is recognized as an opinion leader in the field of human papillomavirus (HPV)associated cancer. Also other team members have clear international visibility.

-The group actively contributes to European organizations, such as the EORTC (European Organisation for Research and Treatment of Cancer) and intensively interacts with national regularity authorities, such as the "Institut National de Prévention et d'éducation pour la Santé" (INPS).

-The team very actively publishes in peer-reviewed, international journals, including very high Impact Factor (IF) journals. 184 peer-reviewed articles in international journals in the field of cancer, 16 in journals with impact factors higher than 10: 3 in the New England Journal of Medicine (IF = 50, one first authorship), 1 in Lancet (IF 28), 7 in the Journal of Clinical Oncology (IF 17), 4 in Lancet Oncology (IF 13) and 1 in the American Journal of Human Genetics (IF 10).

-The group intensively interacts with industrial partners, allowing for the transfer of new findings in more fundamental biological/medical sciences into practical applications.

-The group intensively works together with the University hospital.

-The team works on a highly relevant research topic, an important health issue of great public interest.

-The group has a strong epidemiological research activity and is involved in major European studies, including EUROCARE (EUROpean CAncer REgistry-based study on survival and CARE of cancer patients).

-The team actively and fruitfully collaborates on the local, national and international level.

-The scientific animation of the research group is well established and effective.

 Weaknesses and threats

-The fundamental research is -compared to the clinical research -less developed, being mainly oriented to translational research.

-The animal models used are not always optimal for the given purposes.

-The supervision of the PhD students can be improved/intensified.

-Caution should be paid with respect to the retirement of several leading researchers in the team. Highly active and well recognized researchers, publishing in journals with very high impact factors will leave the group in the next few years. Their successors should be very carefully selected (the maintenance of the permanent positions in the group was confirmed by the Vice-president of the University of Franche-Comté).

 Recommendations

-To install an external advisory board, which could for instance once a year evaluate the progress of the team and give recommendations for the future.

-To improve the quality of the basic/fundamental research of the group, ideally up to the high level of the current clinical research. For example, more relevant animal models could be developed and the primary material available from the University hospital could be more intensively used. Furthermore, special tools might be developed in collaboration with the clinical and epidemiological researchers, e.g. using innovative biomarkers. It would be good to develop more risk-driven basic/fundamental research projects.

-To further increase the number of articles published in very high impact factor journals, eventually by decreasing the total number of articles (increased quality, decreased quantity).

-To better inform the young scientists in the group about their future carrier options.

 Production results

 Specific comments  Appreciation on the results

-The research -in particular the clinical research -is of very high quality and has considerable impact in the field. It is a highly relevant research topic with great interest for the public health: cancer, in particular human papillomavirus (HPV)-associated cancer. This work allowed evaluating quality of life of the patients and identifying: (i) risk factors taking into account socio-economic and demographic determinants, (ii) factors predicting treatment response and (iii) new therapeutic strategies (phase II-III trials).

-The team very actively publishes in peer-reviewed, international journals, including very high Impact Factor (IF) journals. Between 2006 and the proposal submission date in 2010, the group published 184 peer-reviewed articles in international journals in the field of cancer, with only 6.5 "Full time researcher equivalents". Sixteen of them were published in journals with impact factors higher than 10: 3 in the New England Journal of Medicine (IF = 50, one first authorship), 1 in Lancet (IF 28), 7 in the Journal of Clinical Oncology (IF 17), 4 in Lancet Oncology (IF 13) and 1 in the American Journal of Human Genetics (IF 10).

-The contribution of several team members to international organizations, such as the European Organisation for Research and Treatment of Cancer (EORTC) is highly remarkable. For example, one team member is responsible for studies on cancer of the digestive system at the EORTC, serving on consensus conferences and coordinating several national and international clinical trials leading to recommendations. Furthermore, the team contributes to the EUROCARE (EUROpean CAncer REgistry-based study on survival and CARE of cancer patients) work group. The latter is a cancer epidemiology research project on survival of European cancer patients.

 Appreciation on the impact, the attractiveness of the research unit and of the quality of its links with international, national and local partners

The director of the research unit is an opinion leader in the field of HPV-associated cancer. Also other team members are very well visible on the national and international level. A considerable number of young scientists (master/PhD students/post-doctoral fellows) is trained in the group. For instance, 7 PhD degrees and 3 "Habilitation" degrees ("HDR") were obtained by team members since 2007 until the proposal submission in 2010. Some among the young scientists come from abroad, however, the majority is recruited locally. The team successfully applies for external, competitive funding. For instance, projects are funded by the "National Ligue contre le Cancer" (French organization supporting cancer research). The group successfully collaborates with other research teams on a local, national and international level. This includes also collaborations with industrial partners, including big pharmaceutical companies. These are either "real" collaborations, or "research services", which help funding the group's general research activities and allow for the transfer of new knowledge obtained in more fundamental sciences into practical applications. The group works fruitfully with international partners, in long term stable relations, for instance with the "Deutsche Krebsforschungszentrum" (German center for cancer research). Furthermore, the team successfully contributes to international clusters, such as the IARC (International Agency for Cancer Research) CLARA cancer competitive cluster.

The group is actively involved in the organization of national and international scientific meetings. For example, they organized the 4th International Meeting of the Cutaneous HPV Consortium "HPV & Skin Cancer" in 2007 in Besançon.

Team members intensively serve as experts for various institutions, including InVS (Health Monitoring Institute), HAS (French Health Authorities), AFSSET (French Agency for Health Safety for the Environment and for Work), INCa (French National Cancer Institute), Cancéropôle IDF, Cancéropôle GO, (Cancer competitive cluster for Paris and for the west of France), Ligue contre le Cancer (League Against Cancer). The group actively and regularly participates at national and international scientific meetings in their field. Covering the range from fundamental to clinical research, the group facilitates the transfer of new findings in more basic sciences into practical applications.

 Appreciation on the management and life of the research unit

The group is very well managed by its director. A particular challenge is the broad range of backgrounds and activities of the group members (including teaching duties and services provided at the hospital).The scientific animation is very well established and intense. Regular meetings allow for an efficient exchange between the group members. The guidance of the PhD students can be improved: the supervision can partially be intensified and future career options should be more clearly explained. Yet, there is no external advisory board, which could give advice on future directions and strategies. The encouragement of cutting edge projects in the more fundamental sciences could be intensified. Several team members are actively involved in the local "Federative Research Structure", and significantly contribute to the interactions of the local research players, in particular the University hospital.

 Appreciation on the scientific strategy and the project

The research project is solid and feasible. The quality of the clinical research is very high. This includes for example therapeutic trials of phases 2/3, epidemiological research on the evaluation of diagnostic and therapeutic management, quality of care and quality of life, the implementation and coordination of the "Quality of life and cancer" platform of the CGE (competitive cluster for cancer in the east of France), approved and funded by the "Ligue Nationale Contre le Cancer" ("National Ligue Against Cancer) as a clinical research platform as well as the coordination of institutional clinical studies (e.g. by the EORTC -European Organisation for Research and Treatment of Cancer). However, the fundamental research is not very risk-driven and its originality could be improved for instance by the development of innovative and more relevant animal models as well as the more intense use of primary material from the University hospital. The group could more benefit from the fact that they have direct access to such primary material, which could render this part of their research activity more innovative and allow them to perform work at the "cutting edge" of the current state of the art. Most of the allocated resources are bound to specific projects. The recurrent, basic funding is relatively limited and appropriately distributed within the group.



  Date and execution of the visit:

A1:

  Number of permanent researchers with teaching duties (recorded in N1) who are active in research 11 A2: Number of permanent researchers without teaching duties (recorded in N2) who are active in research 0 A3: Ratio of members who are active in research among staff members [(A1 + A2)/(N1 + N2)] 1 A4: Number of HDR granted during the past 4 years 3 A5: Number of PhD granted during the past 4 years 7

Sciences du Vivant et Environnement

				Statistiques de notes globales par domaines scientifiques
						(État au 06/05/2011)
		Note globale	SVE1_LS1_LS2	SVE1_LS3	SVE1_LS4	SVE1_LS5	SVE1_LS6	SVE1_LS7	SVE2 _LS3 *	SVE2_LS8 *	SVE2_LS9 *	Total
		A+	7	3	1	4	7	6		2		30
		A	27	1	13	20	21	26	2	12	23	145
		B	6	1	6	2	8	23	3	3	6	58
		C	1					4				5
		Non noté	1									1
		Total	42	5	20	26	36	59	5	17	29	239
		A+	16,7%	60,0%	5,0%	15,4%	19,4%	10,2%		11,8%		12,6%
		A	64,3%	20,0%	65,0%	76,9%	58,3%	44,1%	40,0%	70,6%	79,3%	60,7%
		B	14,3%	20,0%	30,0%	7,7%	22,2%	39,0%	60,0%	17,6%	20,7%	24,3%
		C	2,4%					6,8%				2,1%
		Non noté	2,4%									0,4%
		Total	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%
	*
		Intitulé UR / équipe	C1	C2	C3	C4	Note globale
	CARCINOGENÈSE EPITHÉLIALE : FACTEURS PRÉDICTIFS ET PRONOSTIQUES	A+	A	A	A	A
	C1	Qualité scientifique et production
	C2	Rayonnement et attractivité, intégration dans l'environnement
	C3	Gouvernance et vie du laboratoire
	C4	Stratégie et projet scientifique

les résultats SVE2 ne sont pas définitifs au 06/05/2011. Intitulés des domaines scientifiques Sciences du Vivant et Environnement • SVE1 Biologie, santé SVE1_LS1 Biologie moléculaire, Biologie structurale, Biochimie SVE1_LS2 Génétique, Génomique, Bioinformatique, Biologie des systèmes SVE1_LS3 Biologie cellulaire, Biologie du développement animal SVE1_LS4 Physiologie, Physiopathologie, Endocrinologie SVE1_LS5 Neurosciences SVE1_LS6 Immunologie, Infectiologie SVE1_LS7 Recherche clinique, Santé publique • SVE2 Ecologie, environnement SVE2_LS8 Evolution, Ecologie, Biologie de l'environnement SVE2_LS9 Sciences et technologies du vivant, Biotechnologie SVE2_LS3 Biologie cellulaire, Biologie du développement végétal


Evaluation report

This report is the sole result of 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 committ ee.

Unit name:

Optimisation des Régulations Physiologiques The EA 4324 ORPHY (Optimization of the Physiological Regulations) is a research unit in animal and human physiology. The ORPHY team, active in the field of Biology-Health, investigates physiological mechanisms in cardiovascular and metabolic adaptations or alterations, aiming at improving clinic management in terms of prevention and therapeutic strategies. The unit combines clinical and fundamental approaches through the use of several animal models. ORPHY acquired an expertise in the evaluation of the effects of environmental constraints (hyperbaric physiology, physical exercise, nutrition) and of pathologic states on the physiological performances (metabolic, cardiovascular…).

The ORPHY Team is located on the campus of the faculty of Sciences and Technology of the University of Bretagne Occidentale (UBO). The ORPHY lab is constituted of 31 members: 15 professors and associate professors, 2 hospital practitioners, 5 (2.5 FTE) administrative and technical members BIATSS and 2 engineers under temporary contracts, who come from 4 faculties of the UBO (Sciences and Technology, Sciences of the Sport and Education, Medicine and Sciences of Health, Lettres and Social sciences).

The team MuST (EA 1274) originates from the EA-4326 "Facteurs nerveux et structuration tissulaire" originally headed by Mr Maxime GIOUX and now headed by Ms Marie-Agnès GIROUX-METGES. MuST has already been evaluated by HCERES and will join ORPHY for the next contract in 2017.

Management team

The ORPHY unit is headed by Ms Christine MOISAN.

HCERES nomenclature

SVE1 LS4: Physiology, physiopathology, medical systemic biology

Scientific domains

Biology, medicine and health, hyperbaric, shock, exercise, environmental extreme conditions.

Unit workforce

Unit workforce

Number EA4324 had focused on 2 main research axes, one concerning marine biology and the second health biology. In 2011, following the recommendations of the previous evaluation by AERES, the group made a major effort of thematic convergence, which led them to dismiss the ecophysiology axis of their research. Thus, between 2011 and 2015, a great effort was made to share expertise and experimental approaches between the different members of the team. Since 2011, their scientific main goal has been to study the physiological mechanisms involved in cardiovascular and metabolic adaptations or alterations, in particular in response to stressful environmental conditions (hyperbaric conditions, exercise, nutrition, haemorrhagic and septic shocks) fields in which this team of researchers has a great expertise. A large part of the research concerns the study of muscle physiology, namely skeletal and smooth vascular muscles and of biological responses to various extreme conditions.

Global assessment of the unit

As compared to the previous evaluation in 2010 there has been a significant improvement in the scientific production (IF from 3.4 to 4.4), in the number of PhD theses (11 thesis defended) and in the focus of scientific research in spite of the reduction in the number of researchers (from 18 to 16). In particular, they followed the advice given to them in 2010 to redirect their scientific interest, and they dismissed the ecophysiology topic that was out of focus in relation to the new project. Moreover, even if a second group (MuST) will join ORPHY in 2017, they won't increase the number of research topics. The unit is still combining clinical research and basic science, although not always in a well-connected manner. They also have improved their technical collaboration by sharing different techniques originally mastered by each team.

Strengths and opportunities in the context



large number of permanent researchers (n=18), although recruitment of an assistant engineer and an assistant professor would be beneficial;  good involvement in local and regional master courses;

 good level of attractivity, mainly due to the international ITN Marie Curie "PHYPODE" project;

 efforts made to reinforce the administrative team by hiring a full time officer;

 efforts to maintain their unique and internationally acknowledged expertise on hyperbaric medicine with dedicated unique and specific technical devices (small animal and isolated cells hyperbaric chamber);  quality of young scientists and physicians involved, some of them carrying the potential of becoming PIs.

Weaknesses and threats in the context

 not enough HDRs (9 for ORPHY and 3 for MuST);  no full time researcher or engineer, in particular lack of a permanent engineer and not only a tenured position in the team; there is a risk of losing the expertise in small animal hyperbaric chamber with the retirement of a technician;  disparity in international reputation of the team members;

 limited level of international interaction, except in the hyperbaric field as exemplified by the PHYPODE project;

 uneven quality of technical people recruited, ranging from limited skills to high level professional capabilities, as exemplified by the development of a small animal hyperbaric chamber (this also raises the problem of how to maintain such technical expertise when the technician currently in charge of this approach will retire);  limited connections between the clinical topics and the basic research conducted in the 2 teams (MuST and ORPHY);  absence of post-docs;

 uneven combination of some too traditional methodological approaches with innovative approaches, such as the hyperbaric chamber which is unique in this field worldwide as well as the pressure chamber microscopy developed by this team;  sustainability of the post "PHYPODE" project: there is a need to define what the follow up of this project will be.

Recommendations

The committee recommends:

 to increase the link between basic and clinical research, facilitating the development of translational and precision medicine; the committee feels that "muscles" (both skeletal and smooth) could represent a common key word to construct a collaborative project;

 to focus on fund raising in order to hire full time researchers on contracts (and to ask to the university for obtaining permanent positions) and full time administrative personnel (currently only available for 20% of their time);

 to increase the level of international interactions and networking, starting from post-doctoral fellows up to young researchers;

 to try to further increase the quality, the impact (publishing also in more general journals with larger audiences) and the number of publications; also, thanks to an increased international networking, to try to increase the quality and the size of consortium to carry out the projects;

 to improve the exchanges between the two joining labs by focusing on methodological aspects and innovative technologies in their respective research fields;

 to aim at a geographical re-localization which may facilitate better interactions. The efforts of collaboration with the other units of the site need to be reinforced as well as the link between clinical and basic research, facilitating translational development.

  , Université d'Angers Mr Jean-Jacques RISSO, IRBA, Service de Santé des Armées, Toulon Ms Clarisse VANDEBROUCK, Université de Poitiers (representative of the CNU) Scientific delegate representing the HCERES: Mr Patrick LACOLLEY Representative of supervising institutions and bodies: Mr Pascal GENTE, Université de Bretagne Occidentale Head of Doctoral School: Mr Christian BROSSEAU, Doctoral School n° 373 "Santé, Information-Communications, Mathématiques, Matière -SICMA" 1  Introduction History and geographical location of the unit



  complementary expertise of MuST and ORPHY;  collaboration with clinicians (cardiologist and intensive care unit personnel based at the CHRU Cavale Blanche);  collaboration with the lung function testing unit at the CHRU (headed by Ms Marie-Agnès GIROUX-METGES);

  Optimization of Physiological Regulations) is a research unit interested in animal and human physiology. They combine clinical and basic approaches through the use of different animal models. ORPHY was created in 2008 following the reorganization of the EA 3879 (Physiology Unit Comparative and Integrative), with the objective to structure the Brest physiology community in terms of research and training. Between 2008 and 2011,

		on	Number on
		30/06/2015	01/01/2017
	N1: Permanent professors and similar positions	16	17
	N2: Permanent researchers from Institutions and similar positions	2	4
	N3: Other permanent staff (technicians and administrative personnel)	3 (FTE)	3 (FTE)
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)
	N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.)	1
	N6: Other contractual staff (technicians and administrative personnel)	1
	N7: PhD students	6
	TOTAL N1 to N7	29
	Qualified research supervisors (HDR) or similar positions	9
	Unit record	From 01/01/2010
		to 30/06/2015
	PhD theses defended		11
	Postdoctoral scientists having spent at least 12 months in the unit		2
	Number of Research Supervisor Qualifications (HDR) obtained during the period
	2  Overall assessment of the unit
	Introduction
	The EA 4324 ORPHY (

signed by their chairman." (Article 8, paragraph 5) 2 The evaluation reports "are signed by the chairman of the expert committee". (Article 11, paragraph 2)


president Michel Cosnard

Claudine Schiff

Evaluation report

This report is the sole result of 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 name:

Lymphocyte (LIPaB,ERI29). The unit, dedicated to the studies of normal and pathological B cells, is located at the Brest University Hospital. This location allowed strong interactions with several clinical departments (Rheumatology, Immunology, Hematology, Nephrology-Transplant and Periodontology) providing human models of autoimmunity, lymphoid disease, renal allografts and periodontal disease.

Management team

Mr Jacques-Olivier PERS has been the director of the unit for the current contract (2012-2016) and will head the unit for the next (2017-2022) period.

HCERES nomenclature

SVE1_LS6, SVE1_LS7, SVE1_LS2

Scientific domains

Normal and pathological B-lymphocytes, diagnosis and treatment of B-cell diseases. The research developed upon Mr Jacques-Olivier PERS's taking the direction remained focused on the role of B cells in autoimmunity, but is more balanced between basic and clinical approaches, in comparison with the scientific direction of the previous management. Moreover, due to collaborations with Brest hospital departments, a new research axis have been opened (B-cell on periodontal diseases) in addition to the former autoimmune models (Sjögren's syndrome, Systemic Lupus Erythematous and Rheumatoid Arthritis). Finally, the structuration of specific technical platforms (Flow cytometry, Calcium influx-screening and epigenomics analysis) was undertaken.

Global assessment of the unit

During the 2012-2016 contract, the unit has successfully developed the previously recognized expertise of the former unit head in autoimmunity and B-cell hemopathies (CLL), specifically working on the role of B lymphocytes in such diseases. Moreover, the unit has promoted the analysis of B cells in physiology, with a specific focus on regulatory B cell subsets, which play a central role in regulating the immune response.

The unit benefited of the support and of staff positions from the Brest University and the Brest Hospital. It also obtained substantial financial support from the "Investissements d'Avenir" program (Labex for Immunotherapy Graft Oncology) as well as European support for its participation to the European project on "Innovative Medicines Initiative, IMI". During this contract, four patents have also been filed; two are licensed and started preclinical development.

PhD students from different nationalities constitute a substantial fraction of the unit workforce. Staff members have developed effective national and international collaborations and they actively participate in training and in dissemination of scientific culture.

The quality of science is good to very good and the level of publications was substantially increased during the 2012-2016 contract. An impressive number of in house and collaborative papers have been obtained over the period, with one quarter of them in very good journals.

Strengths and opportunities in the context

The head of the team has developed a national and international visibility and has become a scientific leader in the field of basic and clinical research.

The unit participates to national and international networks and received substantial financial support allowing also personnel recruitment.

Four patents have been filed, two were licensed and two have obtained maturing funds. The unit has developed a new software for reading biopsy slides.

The unit is well-structured (Science and Technology Steering Committee, research seminars, immunopathology meetings, meeting with students….).

Unit members contribute actively to training actions and the unit hosted foreign students.

The team will benefit from the arrival of an associate professor (Chaire d'excellence INSERM/Université de Bretagne Occidentale, UBO) and of a pathologist, expert in Sjögren's syndrome. Thanks to UBO and to the Brest University hospital, a University Lecturer and Hospital Practitioner will be discharged of teaching duties and fully committed to research activities for the five coming years. A bioinformatician position is currently open and will be funded for 4 years by the IMI project.

Follow-up studies by a clinical network have been set up by the team concerning specific autoimmune disease cohorts, and associated with recent and innovative technical platforms (cytometry, calcium, epigenetics,…) giving access to big data production and analysis at an international scale.

Weaknesses and threats in the context

No integrated view (in the report) on the role of immune cells, among which the B lymphocytes, in the context of the autoimmune pathologies studied in the unit.

  Permanent researchers from Institutions and similar positions 1 N3: Other permanent staff (technicians and administrative personnel) 2 Other professors (Emeritus Professor, on-contract Professor, etc.) 1 N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.) 3 N6: Other contractual staff (technicians and administrative personnel) 4 scientists having spent at least 12 months in the unit 2 Number of Research Supervisor Qualifications (HDR) obtained during the period 1 2  Overall assessment of the unit Introduction During the 2012-2016 contract the unit has organized the B-cell research in 3 interdependent themes:  B lymphocyte physiology: characterization of human regulatory B cells, identification of different forms of the B cell survival factor BAFF, analysis of calcium signalling in B cells and epigenetic regulation of B cells;  B lymphocyte pathology: analysis of the role of B cells in autoimmunity, chronic lymphocytic leukemia, kidney graft rejection and periodontal diseases;  B lymphocyte immunotherapies: elaboration of protocols and diagnostic tools, role of intravenous immunoglobulins (Igs) on B cells and new approaches in immunotherapy.

  B et AutoImmunité

	1  Introduction
	History and geographical location of the unit
	Mr Pierre YOUINOU created the group "Immunology and Pathology" in 1983 and this research unit was promoted
	and reconducted as Équipe d'Accueil (EA 2216) from 1992 to 2016. Since, the retirement of Mr Pierre YOUINOU in 2011,
	the team has been led by Mr Jacques-Olivier PERS. It has received the recognition of the INSERM and of the Brittany
	Region for the 2014-2016 period with the name "Laboratory of Immunotherapies and Pathologies of B lymphocyte"
	Unit acronym:	LBAI
	Label requested:	UMR Inserm
	Current number:	EA2216, Inserm ERI29
	Name of Director	Mr Jacques-Olivier PERS
	(2015-2016):
	Name of Project Leader	Mr Jacques-Olivier PERS
	(2017-2021):
	Expert committee members
		Ms Sophie EZINE
	Representatives of supervising institutions and bodies:
		Mr Rémi BRAJEUL, CHU de Brest
		Mr Pascal GENTE, Université de Bretagne Occidentale
		Mr Pascal OLIVARD, Université de Bretagne Occidentale
		Ms Stéphanie POMMIER, Inserm
	Heads of Doctoral Schools:

Chair:

Ms Claudine SCHIFF, Centre d'Immunologie de Marseille-Luminy, Marseille Experts: Ms Ariane BERDAL, Centre de recherche des Cordeliers, Paris (representative of the CNU) Ms Yolande RICHARD, Institut Cochin, Paris (representative of Inserm) Scientific delegate representing the HCERES: Mr Georges BARBIER, Doctoral School n° 373 "Santé, Information -Communications, Mathématiques, Matière -SICMA" Mr Christian BROSSEAU, Doctoral School n° 373 "Santé, Information -Communications, Mathématiques, Matière -SICMA"

signed by their chairman.

Too many projects for the number of full-time scientists.

Many projects are still at the level of descriptive stage and are not put into a general biological perspective.

A high percentage of in house published papers with impact factor < 3.

Recommendations

As already mentioned in the previous AERES report, the lack of full-time scientists and the variety of projects and models lead to some dispersal.

The committee recommends further prioritizing the projects in order to bring all the unit expertise on the most internationally competitive themes.

This refocusing and the recruitment of full-time researchers are absolutely required to increase the frequency of high-level publications and to optimize the visibility of the team's work.

A clear policy for the identification and recruitment in the future of young researchers is needed.


Evaluation report

This report is the sole result of 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 name:

Epigénétique des Infections Virales et des Maladies Inflammatoires Mr Thierry RIGAUD, Doctoral School n°554 "Environnements-Santé".

 Introduction History and geographical location of the unit

The research unit headed by Mr Georges HERBEIN was created in 2012. It was composed of 3 teams located on 3 different sites: the virology team of Mr Georges HERBEIN located in the center of Besançon (former Saint Jacques Hospital), the team of Mr Pierre POTHIER working on enteric virus infections at the university hospital of Dijon, and the team of Mr Patrick PLÉSIAT working on antibiotic resistance in Pseudomonas aeruginosa and located at the university hospital of Besançon (Minjoz) and at the Medical school, both located at a very recent healthcare and university campus of "Les Hauts du Chazal". In the future configuration, the unit will be monothematic and in a unique site, Besançon, within the campus of "Les Hauts du Chazal". The name of the unit will change to "Epigenetics of Viral Infections and Inflammatory Diseases" (EPILAB).

Management team

For the period of 2017-2021, the unit will be directed by Mr Georges HERBEIN. It will be structured into 4 themes, 2 being headed by Mr Georges HERBEIN, while the two others will respectively be headed by Mr Vincent DI MARTINO & Mr Thierry THEVENOT and Mr Eric TOUSSIROT & Mr Daniel WENDLING.

ERES nomenclature

SVE_LS3

Scientific domains

The upcoming unit will explore the molecular mechanisms involved in viral infections and inflammatory diseases. Theme 1 will be dedicated to the identification of proteins controlling HIV latency and to the identification of new molecules allowing to overcome latency. Theme 2 will explore the oncogenic potential of CMV in human mammary epithelial cells. Theme 3 will explore the prognostic value of inflammatory markers in liver cirrhosis. Finally, Theme 4 will explore epigenetic mechanisms involved in the onset and the progression of the chronic inflammatory diseases ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In 2012, at the eve of the last 5-year plan, the unit made the ambitious bet of rassembling two virology labs and two microbiology labs in a same entity split over three different locations. They had the project to consolidate their skills in the exploration of the biology of the pathogens and the inflammatory response these pathogens may induce. For this term, the unit wishes to go back to a simpler structure with a single team located in Besançon, with 4 themes organized within viral infections and inflammatory diseases.

Unit workforce

Unit

Global assessment of the unit

The unit plays an important role in bringing together and structuring local research in the fields of virology and inflammation, and is described by the clinicians as a reliable frame for their scientific projects.

Since the last AERES evaluation in 2010, the unit has maintained quality research, crossing several important milestones especially in the field of HIV and norovirus. The scientific production has remained abundant and several projects are operated in collaboration with local, national, and European partners, in part supported by European funding (FP7), reflecting a good level of visibility. In that context, the unit has endeavoured an abundant publication record in specialty journals and also in journals of more general interest.

The unit stands out by the value of bonds established between clinic and academic research. It is also proactively involved in teaching, with several members participating in the management of master degree courses, and teaching M.Sc. students in the fields of cellular and molecular signaling, host-graft relation, and inflammatory diseases. In parallel, the unit provides M.Sc. and PhD students with training through research.

The refocusing of the unit was an absolutely necessary step. The overall assessment is very good.

Strengths and opportunities in the context

The unit is managed by a group of talented and very motivated clinicians with original ideas and good technical skills.

It is well connected locally and is considered by the clinicians as an essential hub for their research. In that context, it has extensive access to valuable patient material and high level medical expertise.

The theme on cirrhosis appears as the strongest in terms of feasibility and manpower.

The unit also maintains connexions with European networks and sustains a very good reputation within the HIV field.

Weaknesses and threats in the context

Publications are in specialty journals, although these journals are frequently the best within their field.

The European funding is coming to an end, and the projections in terms of funding for the next 5 years is poor.

The low workforce associated with each theme of research is a clear source of concern.

The unit has not managed to attract scientists with full-time permanent research positions.

The unit does not receive any assistance from either technical or administrative staff.

The theme on CMV and breast cancer is still very fragile and has only marginally evolved since the last evaluation.

The theme addressing the role of DNA methylation in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) is suffering from a clear lack of preliminary results.

Scientifically, the unit may be, for some projects, below the critical mass in terms of manpower to face fierce competition. Yet, there seems to be room for further focusing, as the future entity will still be split between 4 different themes each with only limited manpower. In this context, some clinicians associated with the unit are highly implicated in research, while others have a rather limited input due to extensive clinical activity.

Recommendations

The team has to re-evaluate the balance between tasks and manpower, probably by defining more precisely the projects of high priority and associating available staff scientists and post-doctoral fellows with these projects.

PIs should make a priority out of the recruitment of scientists with permanent positions and students, to increase the feasability of the projects.

Members have to be more pro-active in fundraising.

The unit should target more generalist journals.

The new name "Epignetics of Viral infection and inflammatory diseases" may not serve the unit well, as its strength is not in "epigenetics", but rather in infection and inflammation. The committee recommends choosing a name not mentionning "Epigenetics".

  Ms Dina KREMSDORF, Inserm U 1135, Université Pierre et Marie Curie Mr Bruno POZZETTO, Faculté de Médicine Jacques Lisfranc, Université Jean Monnet de Saint-Etienne (representative of the CNU) Scientific delegate representing the HCERES: Ms Sophie EZINE Representative of supervising institutions and bodies: Mr Lamine BOUBAKAR, Université de Franche-Comté Head of Doctoral School: