COSY is a joint initiative of 11 partners, comprising two hospitals (Necker – Enfants Malades – AP HP and Hôpital Mère Enfant – HCL), 6 research groups (including hospital-university instituts (Instituts Hospitalo- Universitaires (IHUs), 3 industrial partners and one patient association. It combines all the necessary skills to propose innovative tools in physiopathology, genetics, imaging and care reorganization.

Conjointly, we aim to re-define a new standard of care and to offer a unique multidisciplinary service organization dedicated to Overgrowth syndromes (OS) patients.













Coordinating partner

〉 Guillaume Canaud

Guillaume Canaud (MD, PhD), RHU COSY scientific coordinator, works in the Renal Division of Necker Hospital and runs the laboratory entitled “Mechanisms and therapeutic strategies in overgrowth syndromes and vascular anomalies”, located within the Institut Necker-Enfants Malades (INEM).

He performed his Residency in Nephrology in Paris. He carried out his PhD degree in molecular and cellular biology at the laboratory of Dr. Fabiola Terzi (INSERM U1151, Necker – Enfants Malades Hospital). Then, he joined Joseph Bonventre’s Laboratory (Harvard Medical School, Boston, USA) to achieve a postdoc. He came back to Christophe Legendre’s team with a Faculty position (Associate Professor) and built his own research group dedicated to translational medicine. He obtained the prestigious European Research Council starting grant (2016) and an ERC Proof of Concept Grant (2017). He received numerous awards including the 2018 Prize Jean Lecocq of the French Academy of Sciences, the 2019 Prize Eloi Collery of the French Academy of Medicine (highest distinction of the National Academy) and the 2019 Ville de Paris Jean Hamburger Prize.

Throughout his career, Guillaume has demonstrated his leadership in coordinating patient care and fundamental research.

Guillaume Canaud leads the laboratory entitled “Precision medicine for diseases of the mTOR pathway” specialized in the understanding of rare disorders linked to the mTOR pathway as well as identification of new treatment for patients. The lab is located within the Institut Necker-Enfants Malades (INEM). INEM is an international biomedical research center located on the Necker Hospital campus and supported by the French National Institute of Health and Medical Research (INSERM-U1151), the French National Center for Scientific Research (CNRS) and the University Paris Descartes. One of INEM’s major strengths is the close interaction between the research labs and the clinical departments, creating a highly dynamic environment and promoting translational and “bench to bedside” activities.

Role in RHU COSY

Guillaume Canaud, as the project coordinator (Inserm partner), will take part in the management of the project (WP1) with the support of Inserm Transfert, a private subsidiary of Inserm under a Public Service Delegation agreement, and the Délégation Régionale Inserm Paris 5 (DR5), a Coordinator that provides logistical support for research structures.

Dr Canaud (sponsored by Inserm) will lead WP3, as such he will work to develop appropriate animal models, test novel pharmacological treatments, and decipher the molecular signature and putative biomarkers of Overgrowth syndromes (OS).

At the same time, as an AP-HP partner, he will be highly involved in all the tasks that concern the delineation and natural history of OS (WP4) and the reorganization of healthcare for OS patients (WP5) but also will participate on the creation of standardized protocols of MRI (Magnetic Resonance Imaging) and elaboration of new tools to explore and follow up bone composition/deformation as well as soft tissue composition and creating a 3D personalized virtual patient (WP6).

The Companies Partners

IntegraGen is a French leading lab in cutting-edge technologies (high-throughput sequencing in particular) combined with the industrialization of processes including design of studies, sample tracking, bioinformatics analysis tools. In addition to its headquarters based in Evry, IntegraGen has installed two internationally renowned sequencing units in Gustave Roussy and Pasteur Institute.

Bérangère Génin

Bérengère Génin is the Director of Bioinformatics at IntegraGen since 2010. She provides her expertise in bioinformatics to IntegraGen genomics activities by performing analyses and development of web applications adapted to the need of researchers and clinicians in the field of SNPs genotyping and high-throughput sequencing. She began her career at Sanofi in 2002, where she worked for eight years as a bioinformatician at the Centre de Génomique Humaine in Evry. She was also responsible for the bioinformatics project at the Centre de Pharmacogenomics de Génome Québec and the Montreal Heart Institute in Canada. Bérengère Génin holds a DESS in Genetics and Bioinformatics.

Role in RHU COSY

IntegraGen will contribute to the search for novel genes causing Overgrowth syndromes (WP2) by performing somatic variant calling and deep whole-exome sequencing (WES) to identify somatic variants in new genes without a priori on their function.

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Kitware SAS is a software research and development company with headquarters in Villeurbanne, a subsidiary of Kitware Inc., with headquarters in Clifton Park, NY. Kitware’s mission is to create, maintain and service open-source software, and to create proprietary products on top of that software. The company has made a worldwide impact on the well-known Segmentation and Registration Toolkit (ITK), The Visualization Toolkit (VTK) and CMake.

Julien Jomier

Julien Jomier is CEO of the European subsidiary of Kitware SAS where he focuses on European business development. Julien received both his B.S. and M.S in Electrical Engineering and Information Processing in 2002 from the ESCPE-Lyon (France) and an M.S. in Computer Science from The University of North Carolina at Chapel Hill (UNC) in 2003. He worked on a variety of projects in the areas of parallel and distributed computing, mobile computing, image processing, and visualization. As a developer of the Insight Toolkit (ITK), Mr. Jomier was involved in applications for stereo reconstruction, model-to-image registration, and vessel analysis. His main areas of research include image-guided surgery and multimodality data fusion as well as computer-aided diagnosis. He is also a main developer for the Image-Guided Surgery Toolkit (IGSTK) and continues to support the Insight toolkit. Prior to joining Kitware, Mr. Jomier was a Faculty Research Lecturer of Radiology at the University of North Carolina and a member of the Computer-Aided Diagnosis and Display Laboratory.

Role in RHU COSY

Kitware will develop novel software algorithms for the segmentation and quantification of drug response and/or surgery from digital imagery in WP6.

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EOS imaging is a global medical device company that designs, develops and markets innovative, low dose 2D/3D full body and weight-bearing imaging, rapid 3D modeling, web-based patient-specific surgical planning, and integration of surgical plan into the operating room that collectively bridge the entire spectrum of care from imaging to post-operative assessment capabilities for orthopedic surgery.

Elisabeth Soubelet

Elisabeth Soubelet is Chief Medical Officer, head of partnerships and innovation at EOS Imaging. She leads the clinical affairs department, conducting clinical research with worldwide renowned musculoskeletal radiologists and orthopedists.  She also drives the innovation roadmap, to explore future technologies or medical fields in partnerships with academic laboratories.

Role in RHU COSY

EOS imaging will develop new tools to monitor in 3D growth and bone deformation at very low dose of radiation. EOS imaging will also explore new imaging mode to characterize and quantify bone and soft tissues composition.

The Other Partners

〉 Mario Pende

Mario Pende (PhD) leads the team for “Cell growth control by nutrients” within Inserm Unit 1151/CNRS/Université de Paris, at the Institut Necker-Enfants malades (Paris). After his PhD in the George Thomas laboratory (Friedrich Miescher Institute, Basel, Switzerland), Mario Pende was awarded the Inserm Avenir contract in 2002, followed by the European Research Council starting grant award in 2008 and European Research Council consolidator grant award in 2013. He received several awards, including the Schlumberger Foundation and the Labbé price from the Academie des Sciences. He has been interested during the last 15 years in how nutritional cues are transduced in the cell through the PI3KCA/mTOR/Akt pathway to impact growth responses, including cell size, cell proliferation, senescence, survival, protein synthesis, and metabolism.

Role in RHU COSY

Mario Pende will work, in collaboration with the project lead, on the identification of pathogenic mechanisms of Overgrowth syndromes (OS) to offer precision and personalized medicine (WP3).

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The Clinical Research Unit (Inserm) manages sponsor activities for the clinical trials of which Inserm is a sponsor. It is involved in leading and coordinating the Clinical Investigation Centers (CIC) which ensure that medical scientific data are generated under optimum quality and safety conditions. It also represents Inserm in the F-CRIN project, an “Investments for the Future” clinical research infrastructure. In addition, this group manages Inserm’s relationship with the competent authorities as the French medicament agency (ANSM) or the French data protection authority, CNIL. The team supports about 80 new studies by year in which around 10% of international studies.

〉 Hélène Espérou

Hélène Espérou (MD, PhD) is currently the head of the Clinical Research Unit at INSERM. She holds a DEA in health economics “Hospital care systems”. She is a hematologist and exerted for 18 years at the hôpital St Louis (AP-HP), having left the clinical activity in 2006 to join several health institutions. She was part of Roselyne Bachelot-Narquin’s cabinet, former French health minister. Throughout her career, she has maintained a strong relationship with the clinical research field.

Role in RHU COSY

Hélène Espérou collaboration will aid in creating an Overgrowth syndromes registry.

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The Institut du Cerveau is a translational neuroscience institute, located at the Pitié-Salpêtrière Hospital in Paris, that brings together patients, doctors, and researchers with the aim of developing treatments for disorders of the nervous system and promptly make them accessible to patients.

〉 Stéphanie Baulac

Stéphanie Baulac, Inserm research directoris and head of the research team, is also “genetics and physiopathology of epilepsies” at the ICM and scientific director of the ICM sequencing core facility (iGenSeq). She is an expert on the genetics of epilepsies and brain malformations of cortical development and is one of the pioneers identifying mutations in the mTOR pathway genes in focal epilepsies (DEPDC5 gene) and somatic variants in cortical malformations of the development. She has obtained the prestigious European Research Council consolidator grant (2015) and obtained the 2019 international Epileptology prize (Michael Prize). She coordinates a research network with neurologists, neuropediatricians, and neurosurgeons to study human epileptic brain tissues.

Role in RHU COSY

As an expert in brain somatic mutations, Stéphanie Baulac leads the WP2, participates in the centralization of molecular diagnosis at the ICM for all patients with brain involvement (WP5) as well as in functional studies related to the mTOR pathway (WP3).

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Necker Enfants Malades Hospital belongs to the Assistance Publique – Hôpitaux de Paris (AP-HP) which is a public health establishment and the largest teaching hospital system in Europe. Necker Hospital provides a range of medical specialties and pediatric surgeries, a pediatric emergency reception service, a type 3 maternity, and highly specialized adult services. It is a referral hospital for the treatment of heavy and complex pathologies and an essential player in the management of rare diseases, chronic diseases, and disabilities. The hospital has 35 teams involved in 16 European Reference Networks (ERN) including the ERN SKIN which is coordinated at Necker.

Nadia Bahi-Buisson

Nadia Bahi-Buisson (MD, PhD) is a professor at the Department of Pediatric Neurology, Necker Enfants Malades hospital. Researcher at the Imagine Institute INSERM UMR-1163 Paris Descartes University, Paris. She coordinates a group of research on megalencephaly with a Postdoc and 2 PhD students. The focus of her clinical and research studies are megalencephalies, diagnosis and natural history from fetal/prenatal diagnosis to childhood, consequences on neurodevelopment; she also has relevant experience in neurofoetopathology and imaging techniques. She coordinates one of the largest databases for cortical malformations and interacts with the only molecular diagnosis lab for megalencephalies in France.

Role in RHU COSY

Nadia Bahi-Buisson, sponsored by AP-HP, will be highly engaged leading WP4 and WP5. She will be responsible for establishing local coordination of care and a system to follow up patients with PIK3CA-Related Overgrowth Syndrome (WP4), and for creating 4 multidisciplinary expert centers in France to provide the best care to Overgrowth syndromes (OS) patients (WP5).

As a researcher at the Imagine Institute INSERM UMR-1163, Dr Bahi-Buisson will be involved in WP2, specifically, in the development of in vitro tests to assess the pathogenicity of new variants in genes belonging to the mTOR pathway as well as in the development of OS cellular models and drug screening (WP3).

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URC Eco founded in 2007 and currently under the direction of Professor Isabelle Durand-Zaleski, is a publicly-funded research and knowledge unit that is part of the AP-HP consortium. URC Eco’s primary mission is to inform the decision-making process of stakeholders in the health care system, including policymakers, institutions, and professionals in the areas of health economics, health services research, and health policy analysis.

〉 Isabelle Durand-Zaleski

Isabelle Durand-Zaleski is a medical doctor and Professor in Public Health. She is currently the head of the Paris Health Economics and Health Services Research Unit. She carried out her PhD research in economics and management at Paris IX University, France. She holds a Masters in Public Health from Harvard University, Cambridge, MA, USA, and a diploma from the Political Study Institute of Paris (Institut d’Etudes Politiques de Paris). She has been the head of the Evaluation Department in the National Health Authority.

Role in RHU COSY

Isabelle Durand-Zaleski assignment will be to address the cost analysis of the project, in WP7.

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La Suite-Necker is an innovative program for teenagers and young adults with rare chronic diseases followed up at Necker-Enfants Malades hospital (AP-HP, Paris, France) and transitioning from pediatric care to adult care. La Suite-Necker, which includes a dedicated ward at Necker hospital, website and mobile app, offers to adolescents the possibility to meet not only medical professionals (dermatologists, gynecologists …) but also social workers, estheticians, hairdresser, and so on, that are dedicated support them during this phase and help them in enhancing their self-esteem, quality of life and gaining autonomy in their healthcare.

〉 Nizar Mahlaoui 

Nizar Mahlaoui (MD, MPH, PhD) is a full-time pediatrician at Necker-Enfants Malades hospital (AP-HP). He coordinates the French National Reference Center for Primary Immune Deficiencies (CEREDIH). He is also a member of the Scientific Council of the French Association for patients with primary immunodeficiencies (IRIS), Chair of the European Society for Immunodeficiencies (ESID), and Chair of the Medical Board of the International Patient Organisation for Primary Immunodeficiencies (IPOPI). He is the funder and medical director of “La Suite”, the Rare Diseases and Chronic Diseases innovative Transition Program Necker Enfants Malades hospital (for which he was awarded with the Prix galien in Dec. 2019).

Role in RHU COSY

With the purpose of improving Overgrowth syndromes (OS) patients’ socialization, La suite, headed by Dr Mahlaoui, will be implemented to the different expert centers (WP7).

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Hospices Civils de Lyon (HCL) is the 2nd university hospital center in France with 14 establishments (including 3 generalist establishments, 7 specialized establishments and 4 geriatric establishments) that encompasses a wide range of human, technical and logistical means to carry out their care, teaching, research, medical innovation, prevention and health education. Additionally, HCL is involved in the treatment of childhood cancers (IHOPe), in partnership with the Léon Bérard Center.

Laurent Guibaud

Laurent Guibaud (MD) is a national radiologist expert in superficial vascular lesions and Overgrowth syndromes (OS) and is the coordinator of the multidisciplinary consultation for superficial vascular anomalies at the CHU of LYON. He is the founder of the “Journée Riche-Enjolras”, who is an annual meeting of the French multidisciplinary teams in charge of vascular anomalies. He was involved in many national and international studies related to the diagnosis and treatment of superficial vascular lesions.

Role in RHU COSY

The WP6 leader, Laurent Guibaud, will provide advice and expertise, as necessary, to transform the radiological diagnosis and follow up of OS patients.

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Imagines genomics core facility provides high-throughput genotyping, sequencing and gene expression services to the Necker research community. Experimental design, analysis and interpretation of results are performed on an interactive basis with investigators and the bioinformatics facility (Institut Imagine/Paris Descartes University).

Christine Bôle-Feysot

Christine Bôle-Feysot (PhD) is the genomic plate-form manager at the Imagine’s genomics core facility. She carried out her PhD research in molecular endocrinology at Paris Sud XI University. She is an expert in next generation sequencing and DNA microarrays.

Role in RHU COSY

Christine Bôle-Feysot and her team will be undertaking the deep exome analysis as well as the panel diagnostic (WP2).

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The Foundation for Rare Diseases (FFRD) is a non-profit organization of scientific cooperation. Its mission is to accelerate research for all rare diseases by supporting research and researchers. The granted projects concern decrypting diseases, assisting in diagnosis by identifying the cause of diseases, helping to develop new treatments, and improving daily rare disease patient and family life. 

FFRD acts as a federative hub to fund research and accelerate scientific, clinical, and social innovation by stimulating cross-sector cooperation towards effective healthcare to the benefit of RD patients.

Prof. Daniel Scherman

Prof. Daniel Scherman is the FFRD Director since 2017. He has been elected chairman of the Health and Medicine Committee of EURASC, European Academy of Sciences. He received several awards, Main Prize of the French National Academy of Sciences – Emilia Valori Prize for the Applications of Sciences, Experimental Uveitis Research Award – Deutsche Uveitis Arbeitsgemeinschaft, and prize of the French National Academy of Medicine. His main discoveries and issued and developed patents concern gene delivery vectors, including chemical vectors and electroporation delivery methods, biosafe miniplasmids for gene therapy, plasmid purification techniques, and bioimaging.

Role in RHU COSY

In the WP8 of which the FFRD is the leader, Anne-Sophie Blancher, Communication and partnership manager, will have a central role in the communication and dissemination of RHU COSY findings : website, workshops …

In the WP7-3, Diana Désir-Parseille, Research administration manager will focus the 9th edition of the Social sciences and Humanities (SSH) annual call for research proposals of the FFRD on Overgrowth syndromes (OS), to allow better understanding of individual, familial and psychosocial consequences of OS and to improve care and everyday life of patients and their families.

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The Association Syndrome Cloves was created by the parents of a sick children, with the aim of bringing together affected patients and help them to share their experiences, providing information on this disease and raising funds for research.

Role in RHU COSY

Anne-Sophie Lefeuvre, president of the association, participates as a consultant in the conception of communication media.