Postdoctoral Fellow

Natividad Alquézar Artieda

Profile

My curiosity in understanding the molecular mechanisms of human diseases drove me to pursue my doctoral studies. I graduated with a master’s degree in Biomedicine from Barcelona University. Afterward, I earned a PhD in Molecular and Cell biology, genetics, and Virology at the end of 2023 at Charles University in Prague, Czech Republic. My dissertation thesis focused on studying the correlation between the metabolic profile of leukemic cells with the disease outcome and the metabolic rewiring of leukemic cells upon L-asparaginase treatment (a crucial chemotherapeutic agent in leukemia therapy). Both research goals aim to improve the therapy of pediatric leukemic patients. This research gave me the experience of determining the metabolic phenotype of cancer cells and the drivers of metabolic rewiring in leukemia. Currently, my scientific interest has moved into antioxidant mechanisms, immunology, and the effects of the dysregulated metabolism of cancer cells on the tumor microenvironment. In my new project, I aim to unravel the metabolic features of leukemic cells that disturb T-cell functions that boost tumor progression.

Project description

Revealing metabolites modulating immunosuppression in AML-TME

Acute myeloid leukemia (AML) is a highly aggressive disease with a surging incidence and a high relapse rate, which highlight a pressing need for advancements in AML therapies. A critical aspect of AML progression involves immune system evasion, yet the precise mechanisms that allow AML blasts to escape immune cells are not fully understood. To facilitate proper immune function, the tumor microenvironment (TME) must be nutrient-rich without toxic components, which remains a biological challenge due to the dysregulated metabolism of AML. Leukemic cells -in their uncontrolled clonal expansion process- probably exhaust extrinsic pro-proliferative metabolites and nutrients from the bone marrow (BM) while releasing toxic waste products into this niche, thus creating a poor environment for the normal function of resident immune cells. In ReveAL, we will address whether AML cells drive immune defense evasion through an orchestrated mobilization of metabolites in the BM-TME. To achieve our aim, we will generate genetically modify AML cell lines by altering the expression of selected transporters showing significant prognosis relevance. Subsequently, we will delve into characterizing the intrinsic metabolic changes within AML and assessing the impact of these genetic alterations on T-cell activation and cytotoxic activity. To this end, we will establish flow cytometrybased screening assays and a comprehensive in vitro BM-TME model simulating the presence of mesenchymal stromal cells, immune cells, and a hypoxic environment. The most promising transporters identified in altering T-cell response in vitro will undergo further scrutiny using RNA-seq, substrate quantification methods and SCENITH™. Finally, we will validate our results in an in vivo
system. In sum, we endeavor to unearth novel, tumor-specific modulators of immune activity in the BM-TME, which may hold promise for targeted interventions aimed at re empowering the immune system against AML cells.

Free keywords: AML, METABOLISM, SOLUTE, TUMOR MICROENVIRONMENT, T CELLS.