Christelle Borel
Dr
Christelle Borel

Deciphering single-cell gene markers of leukemic stem cells

The heterogeneity of tumours seriously limits current treatment options. This study proposes to explore the heterogeneity of acute myeloblastic leukaemia by taking advantage of the expertise in single-cell gene sequencing developed by Dr Borel and the flow cytometry capabilities developed by Prof. Matthes, Department of Haematology. The goal is to fully sequence a single cell classified according to the phenotypic characteristics of stem cells, by comparing stem cells from healthy individuals with those from patients with acute myeloblastic leukaemia.

Youssef Hibaoui
Dr
Youssef Hibaoui

Understanding molecular mechanisms of leukemia in Down syndrome with a novel induced pluripotent stem cell-based disease model

This project is an extension of a previous project supported by the Foundation, which investigated molecular abnormalities in leukaemias associated with Down syndrome. The project follows an original model made possible by the availability of a rare biological resource: cells from identical twins who differ only by the fact that one carries the additional chromosome of Down syndrome. In the project, the twins’ stem cells are analysed and differentiated according to their erythroid and megakaryocyte lineages. The aim is to identify the molecular or epigenetic events that may lead to the development of acute lymphoblastic or myeloblastic leukaemias in this clinical setting.

Serguey I. Nikolaev
Dr
Serguey I. Nikolaev

Investigation of driver mutations in acute lymphoblatic leukaemia cases in children with Down syndrome

Dr Nikolaev has spent several years researching acute lymphoblastic leukaemias, which affect the development of Down syndrome children. His initial research, which also received funding from the Foundation, revealed several molecular abnormalities that could potentially be addressed by targeted therapies. The aim of this project is to identify all the genetic abnormalities present in this group of leukaemias, using state-of-the-art molecular techniques. Dr Nikolaev’s research makes use of a cell bank containing material from 50 patients with Down syndrome-associated leukaemia, collected at time of diagnostic and after relapse. This will enable identification of the nuclear “accidents” responsible for recurrences and suggest new therapeutic strategies.

Olivier Preynat-Seauve
Dr
Olivier Preynat-Seauve

Landscape of viral signatures in blood products for transfusion: the use of next generation sequencing

The spread of HIV through contaminated blood products is still fresh in everyone’s memory. The question investigated by Dr Preynat-Seauve and his team is whether other known or unknown viruses might be present in blood products despite the stringent screening measures applied today. The team plan to identify gene sequences from non-human material in samples of human blood using a “metagenomic” approach, which they fully developed and validated in previous research. That research eliminated the hypothesis that viral particles are present in cerebral tumours (glioblastomas). This project proposes to adopt the same approach, which uses a combination of genetic and bioinformatic methods. A negative result (no viral particles found) would have considerable impact on blood donation and information provided to the public. Conversely, a positive result would allow further preventive measures to be implemented.

Bernhard Wehrle-Haller
Dr
Bernhard Wehrle-Haller

Metabolic control of hematopoietic stem cell/niche adhesion

Stem cells play an essential role in the ability of certain leukaemias to resist treatment. They function as a continuous source of cancerous cells by hiding in areas of the bone marrow known as “hematopoietic niches”. Dr Wehrle-Haller and his team have endeavoured for several years to gain a better understanding of the conditions that allow stem cells to hide in hematopoietic niches. Previous research has shown that these cells are in a state of quasi hibernation, due to low oxygen (hypoxic) conditions and low energy needs (slow metabolism). The team aims to test the hypothesis that hypoxic and slow metabolic conditions modify the expression and function of cell adhesion molecules (β1 integrin and c-Kit), thereby creating the conditions for the cell to survive in its protective environment. If the hypothesis is confirmed, it would open up important new possibilities, including.

1) New treatments targeting leukaemic stem-cells in protective niches.

2) Improved methods for recruiting physiological stem cells, which are crucial for both autologous and allogeneic bone marrow transplantation.

DrAlberio2
Dr
Lorenzo Alberio

Platelet procoagulant activity : intracellular signalling pathways in platelets from patients with myeloproliferative neoplasms

This project aims to identify the molecular causes associated with the haemorrhages and thromboses that often affect people suffering from myeloproliferative syndrome. He proposes to compare platelets from 50 healthy individuals and 100 patients with myeloproliferative syndrome by characterising them using a combination of flow cytometry, functional methods (procoagulant activity), cellular methods (ion flow, changes PH) and molecular methods (phosphorylation levels). The goal is to identify biomarkers associated with these patients’ risk of haemorrhage or thrombosis.