Research team
Expertise
Dedicated and passionate molecular biologist with broad experience in cell death, ferroptosis, cancer and mitochondria research. Research experience includes writing project reports, proposals and scientific papers in international peer-reviewed journals. Teamwork oriented with excellent organizational skills. Since 2018 I have been working in the field of ferroptosis induction as a new therapeutic strategy against cancer. Specifically, I worked on elucidating the molecular mechanisms of ferroptosis induction using mitochondrial uncoupling compounds and novel iron oxide nanoparticles. My current scientific interest is understanding how the epigenetic modifications affect ferroptosis susceptibility/resistance in neuroblastoma and how reverting these changes could recondition cells to ferroptotic cell death. As a former chemist, I also have experience in the synthesis and physicochemical characterization of nanomaterials for biomedical and industrial applications. PROFESSIONAL EXPERIENCE: From 01/09/2023 to current date: University of Antwerp, Department of Biomedical Sciences, Vanden Berghe lab, Postdoctoral scholarship holder, Studying the epigenetic regulation of ferroptosis in high-risk neuroblastoma. Supervised by Dr. Tom Vanden Berghe (PI) From 01/07/2018 to 30/06/2022 (1 year: 3 months each year except 2020): VIB-UGent Center for Inflammation Research (IRC), Ghent, Belgium, Analysis of the anti-cancer potential, as ferroptosis inducer agents, of novel mitochondrial uncoupler compounds and superparamagnetic iron oxide nanoparticles in experimental models of neuroblastoma and fibrosarcoma. Supervised by Dr. Peter Vandenabeele (PI), Dr. Tom Vanden Berghe (PI), and Dr. Gilberto L. Pardo-Andreu (PI). From 07/02/2018 to 10/01/2023: Institute of Pharmacy and Food (IFAL), University of Havana (UH), Havana, Cuba, Ph.D. student, Molecular Mechanisms of Nemorosone-induced Ferroptosis in Cancer Cells. Supervised by Dr. Gilberto L. Pardo-Andreu (PI). From 01/09/2015 to 21/07/2023: Institute of Pharmacy and Food, UH, Havana, Cuba, Research Associate and Assistant Lecturer for undergraduate students (subject: Spectroscopy). From 02/09/2013 to 17/07/2015: Highest Institute of Technology and Applied Sciences (InSTEC), UH and Laboratory of Environmental Analysis, Havana, Cuba, Synthesis and characterization of TiO2 and g-Fe2O3 nanoparticles for the remediation of polluted water. Supervised by Dr. Ulises Jáuregui Haza (PI), Dr. Ernesto Peláez Abellán (PI), Dr. José Raúl Correa (PI). From 03/09/2012 to 19/07/2013: InSTEC, UH, Havana, Cuba, Chemical-physical analysis of molecular self-assembly processes of aqueous mixtures of polyelectrolyte:surfactant. Supervised by Dr. Hansel Comas Rojas (PI). From 03/10/2011 to 20/07/2012: Center for Technological Applications and Nuclear Development (CEADEN), Havana, Cuba, Synthesis and characterization of controlled drug delivery systems based on hydrogels. Supervised by Dr. Manuel Rapado Paneque (PI). EDUCATION: Institute of Pharmacy and Food, UH: Doctor degree (Ph.D.) in Pharmaceutical Sciences. Successful PhD defense on 10/01/2023. Thesis: Molecular Targets of Nemorosone-induced Ferroptosis in Cancer Cells Institute of Pharmacy and Food, UH: Master degree (M.Sc.) in Pharmacology, 04/10/2017. GPA 3.88 (4.00 scale). Thesis: Anticancer potential of new dihydropyridine derivatives. Toxic effects on mitochondria Highest Institute of Technologies and Applied Sciences, University of Havana: University degree (B.Sc.) in Radiochemistry, with honors and distinction (summa cum laude), 03/07/2015. GPA 3.83 (4.00 scale). Thesis: Synthesis of g-Fe2O3 and TiO2 nanomaterials for the remediation of polluted water with paracetamol
Mapping (+)-jq1-chromatin interactions to characterize its ferroptosis-sensitizing effect.
Abstract
Neuroblastoma (NB) is the most common extracranial solid tumor in children and, at the same time, the leading cause of cancer-related death in childhood. The main clinical problem is found in patients diagnosed with high-risk NB, in whom long-term overall survival is very low despite the different therapeutic strategies implemented. Different patterns of sensitivity to ferroptosis induction have recently been reported in NB cell models representative of high-risk disease. Ferroptosis is a regulated cell death subroutine mediated by iron-dependent excessive lipid peroxidation, which may function as a physiological tumor suppressor mechanism. However, molecular resistance pathways that circumvent ferroptotic vulnerability in high-risk NB have also been found. Recently, we stratified several neuroblastoma cell lines based on their sensitivity to ferroptosis-inducing compounds like ML162 and IKE. We observed that SH-SY5Y and SK-N-BE(2)-C NB cells are particularly resistant to ferroptosis. On the other hand, as part of a selective drug screening based on ferroptosis text mining, we identified the BRD4 inhibitor (+)-JQ1 as a novel epigenetic regulator of ferroptosis that resensitizes both cell lines to IKE- and ML162-induced cell death. Nevertheless, (+)-JQ1-mediated BRD4 inhibition appears to play a dual role in the regulation of ferroptosis: it represses or promotes ferroptosis depending on the cellular epigenetic context. Therefore, we postulate that (+)-JQ1 might have other molecular targets than BRD4, which might be cell type or tumour specific. Here we aim to perform a multi-omics approach based on two different high-throughput sequencing-based methods to unravel how (+)-JQ1 reconditions high-risk neuroblastoma cells to a ferroptosis-sensitive chromatin state. We will combine a novel developed epi-drug-chromatin-interactome profiling technique (Chem-map, reported this year) with ATAC-seq to provide more holistic epigenetic insights into the mechanisms of (+)-JQ1-mediated sensitization to ferroptosis in neuroblastoma. Finally, the proof of concept results, to be obtained within the context of this BOF SRG application, will be crucial to prepare successful follow up postdoc applications (MSCA, FWO, EMBO…) to identify druggable epigenetic targets of ferroptosis resistance and pave my way in academic research.Researcher(s)
- Promoter: Fernández Acosta Roberto
Research team(s)
Project type(s)
- Research Project