A5063956593- Chronic Lymphocytic Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- CAR-T cell therapy research
- Cancer-related Molecular Pathways
- Lipid metabolism and disorders
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
- Single-cell and spatial transcriptomics
- PI3K/AKT/mTOR signaling in cancer
- Cancer Immunotherapy and Biomarkers
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- ATP Synthase and ATPases Research
- Amino Acid Enzymes and Metabolism
- TGF-β signaling in diseases
- Calcium signaling and nucleotide metabolism
- Cholesterol and Lipid Metabolism
- Lymphoma Diagnosis and Treatment
- Genomics, phytochemicals, and oxidative stress
- Diabetes Treatment and Management
- Immune cells in cancer
- MicroRNA in disease regulation
University of Amsterdam
2021-2025
Amsterdam University Medical Centers
2021-2025
Oncode Institute
2022-2024
Cancer Center Amsterdam
2022-2024
Lymphoma Research Foundation
2023
Universitat de Barcelona
2016-2022
Institute of Infection and Immunity
2022
Departament de Salut
2018-2022
Institut d'Investigació Biomédica de Bellvitge
2016-2018
In human cancers, transforming growth factor-β1 (TGF-β1) plays a dual role by acting as both tumor suppressor and promoter of metastasis. Although TGF-β1 contributes to the metabolic reprogramming cancer cells tumor-associated stromal cells, little is known molecular mechanisms connecting this cytokine with enhanced glycolysis. PFKFB3 homodymeric bifunctional enzyme, belonging family 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases, that controls conversion fructose-6-phosphate...
Abstract Autologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction prevails. In CLL, disturbed mitochondrial metabolism has been linked to defective activation and proliferation. Recent research suggests that lipid regulates function differentiation T cells, yet its role CLL remains unexplored. This comprehensive study compares patients healthy donors, revealing critical dependence on exogenous cholesterol for human expansion...
Hyperactivation of the KEAP1-NRF2 axis is a common molecular trait in carcinomas from different origin. The transcriptional program induced by NRF2 involves antioxidant and metabolic genes that render cancer cells more capable dealing with oxidative stress. TP53-Induced Glycolysis Apoptosis Regulator (TIGAR) an important regulator glycolysis pentose phosphate pathway was described as p53 response gene, yet TIGAR expression detected p53-null tumors. In this study we investigated role...
CD40 signaling upregulates BCL-XL and MCL-1 expression in the chronic lymphocytic leukemia (CLL) lymph node microenvironment (TME), affording resistance to BCL-2 inhibitor venetoclax (VEN). VEN therapeutic setting after long-term laboratory selection has been linked metabolic alterations, but underlying mechanism(s) are unknown. We aimed here discover how stimulation as a model for TME-mediated changes, affects sensitivity/resistance. increased oxidative phosphorylation (OXPHOS) glycolysis,...
Abstract Acquired T-cell dysfunction is common in chronic B-cell malignancies. Given the strong connection between metabolism and function, we investigated metabolic alterations as basis of induced by malignant cells. Using cell lines human peripheral blood mononuclear cells, first established a model that recapitulates major aspects cancer-induced dysfunction. Cell derived from lymphocytic leukemia (CLL) (PGA-1, CII, Mec-1), but not other malignancies, altered metabolome generating...
The glycolytic modulator TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) is overexpressed in several types of cancer has a role metabolic rewiring during tumor development. However, little known about the this enzyme proliferative tissues under physiological conditions. In current work, we analysed TIGAR primary human lymphocytes stimulated with mitotic agent Concanavalin A (ConA). We found that expression was induced through PI3K/AKT pathway, since Akti-1/2 LY294002 inhibitors...
Glucose catabolism, one of the essential pathways sustaining cellular bioenergetics, has been widely studied in context tumors. Nevertheless, function various branches glucose metabolism that stem from 'classical' glycolysis have only partially explored. This review focuses on discussing general mechanisms and pathological implications its branching biology B cell malignancies. We summarize here what is known regarding pentose phosphate, hexosamine, serine biosynthesis, glycogen synthesis...
The tumor suppressor p53 has been described to control various aspects of metabolic reprogramming in solid tumors, but B cell malignancies that role is as yet unknown. We generated pairs functional and knockout (KO) clones from distinct (acute lymphoblastic leukemia, chronic lymphocytic diffuse large lymphoma, multiple myeloma). Metabolomics isotope tracing showed loss did not drive a common signature. Instead, lines segregated according origin. Next, we focused on glutamine crucial energy...
Background: Acquired T-cell dysfunction is a prominent feature in chronic B-cell malignancies, such as lymphocytic leukemia (CLL). This widely assumed to hinder the efficacy of based immunotherapy. T cells rely on metabolic switches initiate and sustain an immune response, namely rapid shift glycolysis accompanied by amplification OXPHOS capacity. Aims: Given link between metabolism function, we aimed at uncovering alterations induced malignant B basis dysfunction. Methods: Using cell lines...
Background: Chronic lymphocytic leukemia (CLL) remains incurable despite availability of targeted therapies. Successful autologous cell-based anti-cancer therapies require functionality and longevity effector cells, features that highly depend on complex metabolic processes. A key feature CLL is the suppression T-cell function, but underlying mechanism still poorly understood. We previously found signs impaired plasticity upon stimulation T cells from patients (van Bruggen, Blood 2019)....
Background: T-cells from CLL patients are dysfunctional and display reduced activation, proliferation cytotoxicity upon in-vitro activation. Whilst the role of glucose metabolism in activated T cells is extensively studied, contribution other energy sources less clear. Fatty acid (FA) lipid uptake involves scavenger membrane transporter CD36. CD36-mediated transport has been identified to (metabolically) modulate intratumoral (both Treg cytotoxic CD8+ cells). However, a potential for CD36...