Despite the significant progress made in understanding Acute Myeloid Leukemia (AML) pathogenesis over the last decades, our clinical progress in treating this disease has lagged behind. Developing new translational research strategies focused on the identification of druggable oncogenic targets is critical to pave the road for successful AML treatment.
Our team focuses on early drug development and innovative approaches towards new target and drug discovery in AML. Our research projects stem at the interface between biology, chemistry and clinical research in order to develop innovative methods, aiming to identify new therapeutic opportunities for patients with AML.
To efficiently translate our results to the clinic and accelerate novel drug candidate’s identification, our team works in close interaction with Saint-Louis hospital hematology clinic and phase I trials department. We also seek to develop academic and industry interactions to accelerate the drug discovery journey in AML. Our discoveries may therefore contribute to novel and more efficacious treatments for this highly aggressive and lethal disease.
Developing physiologically relevant AML models
Relying on meaningful disease models is an essential prerequisite to identify therapeutic alternatives for patients with relapsed/refractory hematological malignancies such as AML.
Driven in large part by therapeutic considerations, our team develops humanized AML mouse models, closely mimicking the physio-pathological conditions of leukemic growth within the bone marrow microenvironment. The engineering and optimization of such innovative and powerful mice models harboring ectopic patient derived leukemia within humanized bone marrow niches will allow large scale therapeutic target discovery.
Studying the niche protective role in AML
Leukemia development and chemoresistance are complex processes that are only partially explained by the intrinsic accumulation of genetic alterations in hematopoietic progenitor cells. Recent findings have demonstrated the key role of the bone marrow niche in sustaining AML and regulating drug resistance.
The goal of our work is to define and validate novel niche-leukemic crosstalk induced dependencies, through innovative and powerful high-throughput large scale screening tools applied to physiologically relevant custom made in vitro and in vivo models.
We also develop a pipeline to validate the identified therapeutic targets and conduct the necessary preclinical steps towards translating our findings to the clinic, including identification of novel biomarkers of response to treatments and synergy studies.
In parallel, we are highly interested in shedding light on the mechanistic underpinnings of the bone marrow-leukemia crosstalk using transcriptomic-, epigenomic- and in vivo microscopy-based approaches.
Deciphering the pathways involved in communications between leukemia and stroma provides a framework for defining and understanding AML microenvironment-related specific dependencies, and a path towards the discovery and preclinical validation of promising therapeutic targets in AML. Concomitant “seed” and “soil” targeting may thus eradicate AML leukemic stem cells and improve patient’s survival.
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