Marc Ansari

Order of application and polymorphisms of busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplantation in children and adult patients mainly in leukemia

Allogeneic bone marrow transplants are always preceded by a chemotherapy treatment called conditioning therapy. The goal of this treatment is twofold: first to eliminate any residual leukaemic cells, and second to allow the transplant to engraft and start to function properly. Huge efforts have been made over the past decades to standardise these preparatory therapies. Nevertheless, their toxicity and effectiveness vary greatly from patient to patient. This could be due in part to individual differences in the effectiveness of enzymatic systems, which influence how quickly the drug is eliminated by the body.
Using a randomised clinical study to test a sequence of two chemotherapy products (busulfan and cyclophosphamide), Dr Ansari proposes to analyse the genes involved in the degradation of these two chemicals. The goal is to identify and characterise the genes determining the speed of degradation. In the long term, a better understanding of these genes would help optimise the therapeutic effect of transplants by boosting their effectiveness and decreasing toxicity

Thomas Matthes

Investigating junctional adhesion molecule C (JAM-C) as a new target for B-cell lymphoma therapy

Cancer cells express a broad range of trans-membranous molecules at their surface. These molecules fulfil many functions. First, they allow the cancer cell to receive information from its microenvironment and occasionally to extract nutrition from it. Second, they transmit messages to the cancer cell, telling it how to move around the body. A therapeutic strategy currently under development consists in blocking the transmission of those messages, thus depriving the cancer cells of information present in their environment, which might otherwise encourage them to grow and spread through the body.
For several years, Dr Thomas Matthes and Prof. Beat Imhof have investigated the physiology and pathology of a molecule called JAM-C (junctional adhesion molecule C). Their many publications have demonstrated the important role of this molecule in regulating the movement of normal lymphocytes throughout the organism. JAM-C is also a prognosis factor for certain lymphomas.
Building on promising preliminary results, this project investigates whether the molecule might be a potential therapeutic target, via a series of animal models available in their laboratories. It also tests the potential for associating these new drugs (antibodies) with other molecules that have either been confirmed for the treatment of lymphomas or are still being investigated

Thomas McKee

Molecular characterization of the « double-hit » variant of diffuse large B-cell lymphomas

Diffuse large-cell B lymphoma (DLBCL) is the most common type of aggressive lymphoma in adults. Diagnosis is based mainly on cell morphology (diffuseness and large size). It has become clear, however, that this category of lymphoma comprises several distinct diseases and that the intensity of treatments cannot be correctly determined based solely on morphological characteristics.
In this project, Drs McKee, Matthes and Delorenzi propose a novel way of characterising the disease at the molecular level in order to identify its subgroups.

Aimable Nahimana

Combinatorial therapeutic strategies with an inhibitor of NAD biosynthesis to optimize drug

The DNA of human cells undergoes multiple alterations ever day. Consequently, cells are equipped with a series of enzymes that act like repairmen, working around the clock to fix malfunctions and errors (DNA repair). Most chemotherapies cause errors at the DNA (gene) level, which then trigger these repair enzymes. The energy needed by this repair activity is supplied in part by NAD (Nicotinamide Adenine Dinucleotide). For several years, Dr Aimable Nahimana has been working on developing drugs that obstruct NAD synthesis as a way of inhibiting DNA repair function in cancer cells targeted by chemotherapy and thus make them more susceptible to treatment.
The goal of this project is to study different combinations of chemotherapy and NAD-inhibitors in order to identify the most promising associations, which could then be tested in clinical trials with leukaemia or lymphoma patients.