Hematopoiesis and Microenvironments
We aim to discover ecological interactions in normal and malignant hematopoiesis by studying:
- Niche determinants of clonal heterogeneity, expansion and relapse in leukemia
- Spatial distribution, competition and cooperation between leukemia clones
- Remodeling and targeting of vascular microenvironments in leukemia and lymphoma
- Physiologic and long-range regulatory systems of hematopoiesis and leukemia
Our lab aims to study the cell-extrinsic regulation of normal and malignant hematopoietic cells at the local and systemic levels, specifically focusing on acute myeloid leukemia (AML) but also on of T-cell acute lymphoblastic leukemia (T-ALL) and B-cell lymphoma.
Landmark studies have deciphered genetic alterations that occur in blood cancers and how this drives their complex clonal structure. Yet, we lack fundamental knowledge of the cell-to-cell interactions occurring between normal and malignant hematopoietic cells and their neighbors in the bone marrow (BM) niche. Specifically, the interaction between leukemic stem cells (LSCs) and niches and the dynamics of inter-clonal competition and cooperation in leukemia remain underexplored. We have previously used intravital microscopy of the mouse BM to record the in vivo behavior of T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) at the single-cell level and to demonstrate how local niches are remodeled in leukemia. More recently, we have shown how iron metabolism is dysregulated in AML, both at the local and systemic levels. Our lab uses pre-clinical mouse models of disease, mouse mutants that enable in vivo mechanistic studies, advanced BM imaging, primary patient samples, cell lines and curated clinical data. We have a collaborative environment and benefit from a close interaction with the clinic, particularly IPO-Porto, as part of the Porto Comprehensive Cancer Center.
If you are interested in discussing our work or applying for a position, please contact Delfim Duarte (email@example.com).
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-22 to 30-JUN-23