Program 6 : Tumor genomics

Program 6 : Tumor genomics

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 – Genomic of tumors

STRENGTHS IN THE FOLLOWING AREAS

Cancer Care:

The tumor genomics teams are mentioned in the table above. They have the largest cancer molecular diagnosis activity in the entire Paris region, mainly driven by the reference hematology centers from St-Louis, but also supplied by a substantial clinical, medical and surgical activity concerning solid tumors such as lung (Bichat Hospital), skin, breast (St-Louis Hospital), and digestive cancers (Beaujon, Bichat and St-Louis Hospitals). The national and international visibility of these activities are major assets. Moreover, another considerable advantage is the presence of translational and basic research units, in which most of the biologists involved in molecular diagnosis conduct their research, in close collaboration with physicians (see table below). These teams lead national tumor discussion boards in hematology.

Moreover, it should be emphasized that genomics of solid tumors is performed in close interaction with pathologists (contribution described in Program 12).

Research:

Basic science:

The translational research teams of GHU Nord use patient’s biological samples in order to refine molecular classifications and predictive criteria in child and adult blood diseases, as well as in some solid cancers. Additionally, several groups perform translational and basic research.

The U944/7212 INSERM/CNRS (Head: J. Soulier) teams at Institut de Recherche St-Louis (IRSL) focus on acute leukemia: A. Puissant (Avenir/ERC), H. de Thé (ERC), J. Soulier, and four 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 and 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 network (acute leukemia, head:  H. Dombret) cover many basic and translational research projects from the St-Louis and Robert Debré Hospital sites. For instance, the ARC project “DYNAMICS” (H. de Thé), aiming at understanding the early Acute Myeloid Leukemia (AML) response to chemotherapy by serial analysis at the single cell expression level, is supported by 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 studies investigating the mechanism of action 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 studies biomarkers of response to immunotherapies in advanced melanoma, using multiomic tools.

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

The UMRS-1131 IRSL (Head: 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 epigenetic modifications impacting clonal behaviour. The main objective is the translation from bench to bedside and from bedside to practice in close collaboration with the clinic (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) is based at Bichat Medicine Faculty and studies the biological mechanism linking lung fibrosis and lung cancer. They benefit from the proximity of the Thoracic Surgery and Transplantation Department, and from their lung fibrosis expert center (see Thoracic Cancers Project). A close collaboration also involves the thoracic oncology team (team from U830 in Curie research center).

The U1149 team 9 (V. Paradis) and U1160 Team 3 (M. Allez) are dedicated to several aspects of digestive oncology. M. Allez’s team focuses 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 dedicated to the impact of metabolic syndrome, and a translational axis on tumor molecular heterogeneity and biomarker development.

Education:

All biologists conducting research in this field are also deeply involved in university education for MDs and basic scientists at Université de Paris. Indeed, they participate or lead many courses:

Participation to Diploma of Advanced Training in Medical Sciences (DFASM, Year 1 of medical school); Université de Paris

  • 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 de Paris

Initiation research course (Parcours d’initiation à la recherche PIR); Université de Paris (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 – Jouenne)
  • Oncogenesis (R. Itzykson – J. Soulier)
    • Semester 2: Oncogenesis basics (R. Itzykson)
    • Semester 4: Implementation of concepts and methods in onco-hematology (E. Clappier – Lhermitte)

Masters

  • Master 1 European Magisterium in Genetics
  • UE28 Oncogenenesis (R. Itzykson – J. Soulier)
  • “Introduction to hematology” (Université de Paris, N. Maslah – S. Giraudier)
  • Masters 2 European Magisterium in Genetics

Somatic genetics of cancers module (R. Itzykson – J. Soulier)

Cellular biology of cancers module (V. Lallemand – H. de Thé)

  • Master 2 Molecular and cellular biology (BMC)

BMCFH Molecular cellular and functional biology of hematopoiesis (S. Giraudier – N. Dulphy)

BBPM Biomolecules, molecular biology and pathology (P. Bertheau)

  • Master 2 Biology, Physiology, Pharmacology of respiration and sleep (MB2PRS)

Biology of respiratory epithelial transformation (G. Zalcman)

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

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

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