Identification and targeting of extrinsic regulators of myeloid malignancies

The bone marrow niche plays a key role in sustaining AML and regulating drug resistance.

Our goal is to define novel niche-leukemic crosstalk induced dependencies, through combining single-cell omic approaches to high-throughput screening tools applied to custom-made in vitro and in vivo models.

Our team develops humanized mouse models, closely mimicking the physio-pathological conditions of leukemic cells growth within the bone marrow microenvironment.

In collaboration with Saint-Louis hospital clinical departments, we develop a pipeline to identify innovative therapeutic targets and conduct the necessary preclinical steps towards translating our findings to the clinic, including identification of response biomarkers and synergy studies.

In parallel, we are highly interested in shedding light on the mechanistic underpinnings of the bone marrow-leukemia crosstalk.

Our findings should open the road for concomitant “seed” and “soil” targeting strategies, resulting in AML leukemic stem cells eradication and patient’s survival improvement.

Patients with AML are at higher risk of early death due to severe infectious complications (sepsis), tissue infiltration by blast cells, leukostasis or tumor lysis syndrome.

Our team investigates the pathophysiological mechanisms underlying these life-threatening complications and their subsequent acute organ failure.

Using in vitro and in vivo models, we focus on endothelial dysfunction’s key role.

In parallel, we are highly interested in how essential cellular and molecular signals triggered by sepsis-induced inflammation alter the bone marrow microenvironment and influence leukemic cells proliferation and AML progression.

Our work aims to uncover novel therapeutic strategies to improve patient survival by mitigating acute AML-associated complications and their potential long-term impact on disease evolution.