Vascular integration in tissue bioengineering to model the complexity of leukemic microenvironment

Diana Passaro, PhD, HDR, leads the 'Leukemia and Niche Dynamics' lab at the Institut Cochin in Paris. After completing her PhD in hematology and oncology at the Curie Institute and a postdoctoral position in leukemia microenvironment at The Francis Crick Institute, she secured a group leader position at INSERM combining expertise in stem cell biology, bioengineering, and translational medicine.

The lab's research focuses on the vascular bone marrow microenvironment in acute leukemia, aiming to identify novel therapeutic vulnerabilities. Despite advances in treatment, leukemia remains a highly aggressive malignancy, and survival rates remain poor due to the disease’s ability to remodel its niche. The team investigates how leukemic cells interact with and reshape the endothelial compartment of the bone marrow, creating a permissive environment for disease progression while impairing normal hematopoiesis.

By characterizing endothelial heterogeneity during leukemia development in mouse models, her team has identified distinct vascular subpopulations and molecular pathways that contribute to leukemic expansion and therapy resistance. To study these interactions in a physiologically relevant setting, they have developed humanized bone marrow organoids and vascularized BM-on-chip models, enabling the dissection of leukemia-endothelium crosstalk and the testing of targeted interventions. Beyond the bone marrow, the lab explores the systemic dissemination of acute leukemia, particularly its infiltration of the central nervous system, where the blood-brain barrier could plays a critical role in shielding leukemic cells from standard treatments.

Through a combination of multi-omics approaches, imaging technologies, and functional studies, the researchers aim to redefine the role of the vascular niche in leukemia and uncover novel therapeutic strategies to restore normal hematopoiesis and improve patient outcomes.