Programme 6 : Genomic of tumors

Programme 6 : Genomic of tumors

PROGRAM LEADERS

Pr Jean Soulier

Pr Jean SOULIER, is physician hematologist at Saint-Louis Hospital and professor of hematology at the Université de Paris. He heads the hospital diagnosis laboratory for hematopoietic neoplasms and the INSERM/CNRS research unit U944. His translational research aims to understand and model in vivo hematopoiesis disorders yielding bone marrow failure, clonal hematopoiesis and subsequent acute leukemia.

Pr Samia MOURAH, is professor of pharmacology at the University of Paris. She heads the tumor genomics and pharmacology department at Saint-Louis hospital and a research group in INSERM/UMR-S 976. Her pharmacogenomic translational project focuses on the identification of biomarkers of response to targeted and immune-based therapeutics for improving personalized medicine. Her basic research is centered on the study of tumor microenvironment crosstalk and the development of selective pharmacological inhibitors.

Dr Nathalie THEOU-ANTON, is a molecular physician at Bichat Hospital. She heads the tumor genomics plateform in the genetics department chaired by Pr BOILEAU. This department is certified by INCA and is a French Reference laboratory (LBMR) for the cancer disciplines in Somatic (lung cancer, digestive cancer, melanoma) and constitutional Oncogenetics predisposition/genodermatosis and Telomeropathies (officially designated by the French Agency of Biomedicine). She chairs with the Pr Zalcman the monthly molecular multidisciplinary staffs; she is a certified Biologist  for SeqOIA (northern sequencing platform of the French national genomic initiative) and an expert for the regional multidisciplinary staff for treatment failure advanced cancers and rare cancers.

HEALTHCARE EXECUTIVES

Brigitte CONILLEAU,
paramedical executive

Véronique MEGRAS,
administrative executive
P6 chiffres clés

STRENGTHS IN THE FOLLOWING AREAS

Cancer Care:

Tumor genomics teams are emphasized in the table above; they have the largest cancer molecular diagnosis activities in the whole Paris area, driven by the reference Hematologic expert centers, from Saint-Louis but also a substantial clinical, medical and surgical activity in solid tumors such as lung (Bichat), skin, breast (Saint-Louis), and digestive cancers (Beaujon, Bichat and Saint-Louis). The national and international visibility of these activities consist of a major strength along with the translational and basic research units in which most biologists involved in molecular diagnosis conduct their research, in close link with clinicians (see table below). These teams lead national tumor boards in hematology.

It should be emphasized that genomics of solid tumors is performed through a close interaction with pathologists (contribution described in Program 12).

Research:

7 Basic science:

  • UMR-S Inserm 976 (St-Louis),
  • U Inserm 1160 (St-Louis),
  • U Inserm 944 (St-Louis),
  • UMR Inserm1131 (St-Louis),
  • U Inserm1149 (Bichat),
  • U Inserm 1152 (Bichat)
  • U Inserm 830 (Curie, team lung cancer shared  with Bichat)

GHU Nord’s translational research teams use patient samples to refine molecular classifications and predictive criteria in childhood and adult blood diseases and in some solid cancers. Moreover, several groups perform translational and basic researches.

U944/7212 INSERM/CNRS (Dir: J Soulier) teams at Institut de Recherche St-Louis (IRSL) focus on acute leukemia: A Puissant (Avenir/ERC), H de Thé (ERC) and J. Soulier, and 4 emergent teams, C Lobry, R Itzykson, E Clappier and L Benajiba. These teams use in vitro and murine experimental models (in vivo functional screen using CRISPR libraries, competitive transplant, genetically modified mice, xenografting of human cells in immunocompromised mice) to investigate leukemogenesis and to pre-clinically evaluate targeted treatments.

The IHU/ANR research project THEMA “National center for precision medicine on leukemia” and the Institut Carnot OPALE (acute leukemia, Dir H. Dombret) network are umbrella that covers many basic and translational research projects from the St-Louis and Robert Debré sites. For instance, the ARC project “DYNAMICS” (H. de Thé), aiming at understanding the early AML response to chemotherapy by serial analysis at the single cell expression level, benefits from supports of THEMA to the Saint-Louis genomics and animal facilities.

In UMR-S 976 IRSL, TEAM Onco-Dermatology and Therapies, the research group “Innovative Therapeutic Targets in oncology” (S Mourah, C Lebbé) focuses on translational and mechanism of action studies of the tumor microenvironment modulators CD147 and Kindlin-3 (using in vitro, ex vivo, PDX models, functional and imaging tools), and the development of selective pharmacological inhibitors. The group also focuses on biomarkers of response to targeted and immunotherapies in advanced melanoma, using multiomics tools.

The “breast cancer team” (UMR-S976 IRSL, J Lehmann-Che) explores combined molecular-radiomics stratification approaches and innovative treatment strategies, notably in triple negative and molecular apocrine sub-groups, with the North Territory-Sénopôle.

UMRS-1131 IRSL (Dir: S Giraudier) research teams focus on hematopoietic chronic myeloid pathologies and normal hematopoiesis, studying clonal evolutions during evolution of Classical Myeloproliferative disorders, Juvenile Myelomonocytic Leukemia and Myelodysplastic syndromes. They also focus on epigenetics modifications impacting clonal behaviour. The main aspect is translation from the bench to bedside and bedside to practice in close link with Clinics (JJ Kiladjian, M Strullu), biological diagnosis (B Cassinat, N Maslah, S Giraudier, H Cavé) and fundamental research developed in the Saint Louis site.

The U1152 team (B. Crestani, R. Borie), in Bichat Medicine Faculty, studies the biological mechanism linking lung fibrosis and lung cancer, beneficiating of large thoracic surgery and transplantation Department, and of their Lung fibrosis expert center (also see Thoracic cancers Project). A close collaboration involves the thoracic oncology team (team from U830 in Curie research center).

The U1149 team9 (V. Paradis) and U1160. Team3 (M. Allez) are dedicated to several aspects of digestive oncology. M. Allez’s team is focused on the effector immune responses of lymphocytes, more specifically T cells and innate lymphoid cells in colorectal cancer using innovative patient-derived models such as multicellular complex organoids. V. Paradis’ team is focused on liver and pancreatic carcinogenesis with an axis on the impact of metabolic syndrome and a translational axis on tumor molecular heterogeneity and biomarker development.

Education:

All biologists involved in this field are also deeply involved in university education for MDs and basic scientists at Université Paris Cité since participating or leading many courses:

Participation to Diploma of Advanced Training in Medical Sciences (DFASM, Year1 of medical school); Université Paris Cité

  • Hematology module (N Boissel),
  • Cancerology module DFGSM3 (S Culine, M Battistella, J Lehmann-Che)
  • Cancerology module (L Quero)
  • Cellular biochemistry bases and genetics of diseases module (J Lehmann-Che, HK Ea C Kannengiesser)

Pharmacology teaching (E Jacqz-Aigrain, S Mourah and P Boutouyrie); Université Paris Cité

Initiation research course (Parcours d’initiation à la recherche PIR) ; Université Paris Cité (H Cavé, J le Goff, F Pagès)

  • Genetics (H Cavé-E Pasmant)
    • Genetics, from gene to drug (H Cavé-E Pasmant)
    • Genetics and Cancer (Y Vial-F Bourdeaut)
  • Clinical and General Pharmacology (E Jacqz-Aigrain)
    • Semester 4: Pharmacology in oncology and hematology (S Mourah and F Jouenne)
  • Oncogenesis (R Itzykson and J Soulier)
    • Semester 2: Oncogenesis basics (R Itzykson)
    • Semester 4: Implementation of concepts and methods in onco-hematology (E Clappier and Lhermitte)

Masters

  • Master 1 European Magisterium in Genetics
    • UE28 Oncogenèse (R. Itzykson and J Soulier)
    • “Introduction à l’hématologie” (Université Paris Cité, N. Maslah and S. Giraudier)
  • Masters 2 European Magisterium in Genetics
    • Module somatic genetics of cancers (R Itzykson and J Soulier)
    • Module cellular biology of cancers (V Lallemand and H de Thé)
  • Master 2 Molecular and cellular biology (BMC)
    • BMCFH Molecular cellular and functional biology of hematopoiesis (S Giraudier and N Dulphy).
    • BBPM Biomolecules, molecular biology and pathology (P Bertheau)
  • Master 2 Biology, Physiology, Pharmacology of respiration and sleep (MB2PRS): module biology of respiratory epithelial transformation (G. Zalcman)

Hematology-Oncology and Biotherapies doctoral school (HOB) (R Itzykson)

Inter-university diploma DIU Oncogenetics (R Benamouzig and D Stoppa-Lyonnet)

MOOC Cancer diagnostic strategies (P Bertheau): https://www.fun-mooc.fr/fr/cours/strategies-diagnostiques-des-cancers/