Lysosomes, acidic, hydrolase-rich cellular organelles, are the final destination of endocytic and autophagic pathways. Cell homeostasis is vitally linked to lysosomal function; malfunction being associated with several chronic pathologies including atherosclerosis, the main cause of cardiovascular diseases. Lysosomes are involved in almost the whole process of atherosclerosis. We aim to contribute to the better understanding of these pivotal organelles in the biology and pathobiology of atherosclerosis.
We expect to:
- Identify the molecular mechanisms underlying lysosomal malfunction
- Understand how lysosomal dysfunction disrupts cellular homeostasis and contributes to the pathogenesis of atherosclerosis
- Translate our findings into clinical applications
Our research currently applies some state-of-the-art techniques including Live-Cell Imaging, EM, InterOmics, Biochemical, Biophysical, and Pharmacological approaches applied to cell lines, primary human cells, human blood vessel organoids, and human tissues.
Projects
- “LYSosome DYSfunction and cellular Senescence in atherogenesis: is there a link?”
01/01/2023 – 31/12/2026
Funded by FCT, Ref 2022.01305.PTDC
Lysosomal dysfunction and cellular senescence are highly complex processes, both playing critical roles in atherosclerosis. However, the potential link between them and the underlying molecular mechanisms remain unclear. Therefore, our aims are to determine whether lysosomal dysfunction drives cellular senescence and to identify the molecular pathways through which senescence contributes to atherosclerosis.
- “Exploring human blood vessel organoids: to study endothelial cell senescence in an atherosclerotic environment”
2025 –2026
Funded by the Twinning on Microphysiological Systems (MPS)
Endothelial cell (EC) senescence has been identified as a major contributor to endothelial dysfunction in various cardiovascular diseases, including atherosclerosis. In this project, we aim to elucidate the pathobiology of EC senescence using human blood vessel organoids exposed to a family of lipids—cholesteryl hemiesters—previously identified by our group in tissues from patients with cardiovascular disease.
- “Identifying novel Drug targets and Affordable Therapeutic interventions for Atherosclerosis using blood vessel organoids”
20/02/2025 – 19/08/2026
Funded by FCT, Ref 2023.13770.PEX
In this project, we propose to identify early altered pathways in human blood vessel organoids (hBVOs) exposed to cholesteryl hemiesters as a model of atherosclerosis. We aim to discover effective therapies for atherosclerosis by modulating these pathways using both targeted and untargeted approaches.
Publications
- Marques ARA, Ferreira IS, Ribeiro Q, Ferraz MJ, Lopes E, Pinto D, Hall M, Ramalho J, Artola M, Almeida MS, Rodrigues G, Gonçalves PA, Ferreira J, Borbinha C, Marto JP, Viana-Baptista M, Gouveia E Melo R, Pedro LM, Soares MIL, Vaz WLC, Vieira OV, Aerts JMFG. Glucosylated cholesterol accumulates in atherosclerotic lesions and impacts macrophage immune response. J Lipid Res. 2025 Jun;66(6):100825. doi: 10.1016/j.jlr.2025.100825.
- Calado RDA, Mendes BB, Conniot J, Ravasco JMJM, Sobral D, Ferreira C, Ferreira R, Rodrigues JC, Santos D, Duarte S, Vieira L, Inácio ÂS, Carrêlo H, Vaz WLC, Gomes JP, Nunes A, Conde J, Vieira OV. Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatally transmitted infections. Matter 7, 2205–2235 June 5, 2024. DOI: 10.1016/j.matt.2024.04.002
- Domingues N, Marques ARA, Calado RDA, Ferreira IS, Ramos C, Ramalho J, Soares, MIL, Pereira T, Oliveira L, Vicente JR, Wong LH, Simões ICM, Pinho E Melo TMVD, Peden A, Almeida CG, Futter CE, Puertollano R, Vaz WLC, Vieira OV*. Oxidized cholesteryl ester induces exocytosis of dysfunctional lysosomes in lipidotic macrophages. Traffic. 2023 Jul;24(7):284-307. doi: 10.1111/tra.12888.
*Selected for the journal cover
- Domingues N, Gaifem J, Matthiesen R, Saraiva DP, Bento L, Marques ARA, Soares MIL, Sampaio J, Klose C, Surma MA, Almeida MS, Rodrigues G, Gonçalves PA, Ferreira J, E Melo RG, Pedro LM, Simons K, Pinho E Melo TMVD, Cabral MG, Jacinto A, Silvestre R, Vaz W, Vieira OV*. Cholesteryl hemiazelate identified in CVD patients causes in vitro and in vivo inflammation. J Lipid Res. 2023 Sep;64(9):100419. doi: 10.1016/j.jlr.2023.100419.
*Selected for the journal cover
- Matthiesen R, Lauber C, Sampaio JL, Domingues N, Alves L, Gerl MJ, Almeida MS, Rodrigues G, Araújo Gonçalves P, Ferreira J, Borbinha C, Pedro Marto J, Neves M, Batista F, Viana-Baptista M, Alves J, Simons K, Vaz WLC, Vieira OV*. Shotgun mass spectrometry-based lipid profiling identifies and distinguishes between chronic inflammatory diseases. EBioMedicine. 2021 Jul 23;70:103504. doi: 10.1016/j.ebiom.2021.103504.
*Commentary in EBioMedicine 70:103526, DOI:https://doi.org/10.1016/j.ebiom.2021.103526.
- Marques, ARA; Ramos, C; Machado-Oliveira, G; Vieira, OV. Lysosome (Dys)function in Atherosclerosis—A Big Weight on the Shoulders of a Small Organelle. Frontiers in Cell and Developmental Biology Vol. 9, 29 March 2021. doi: 10.3389/fcell.2021.658995.
- Gerl MJ, Vaz WLC, Domingues N, Klose C, Surma MA, Sampaio JL, Almeida MS, Rodrigues G, Araújo-Gonçalves P, Ferreira J, Borbinha C, Marto JP, Viana-Baptista M, Simons K, Vieira OV. Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients. Sci Rep. 2018 Oct 3;8(1):14764. doi: 10.1038/s41598-018-33116-4.
- Gibson MS, Domingues N, Vieira OV. Lipid and Non-lipid Factors Affecting Macrophage Dysfunction and Inflammation in Atherosclerosis. Front Physiol. 2018 Jun 26;9:654. doi: 10.3389/fphys.2018.00654.
- Santarino IB, Viegas MS, Domingues NS, Ribeiro AM, Soares MP, Vieira OV. Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis. Sci Rep. 2017 Jul 19;7(1):5812. doi: 10.1038/s41598-017-05687-1
- N. Domingues, L. Estronca, J. Silva, M. Encarnação, R. Mateus, D. Silva, I. Santarino, M. Saraiva, M. Soares, T. Pinho e Melo, A. Jacinto, W. Vaz and O.V. Vieira. Cholesteryl hemiesters alter lysosome structure and function and induce proinflammatory cytokine production in macrophages. BBA - Molecular and Cell Biology of Lipids. February 2017 1862; 2: 210–220. doi: 10.1016/j.bbalip.2016.10.009
Prizes and Awards
- 2025: Best Oral Communication Award, NMS Research Symposium, Lisbon, Portugal (Inês Ferreira)
- 2025: Medal of Merit from the Municipality of Gouveia for dedication to research and an immeasurable contribution to the field of medicine (Otília Vieira)
- 2025: Bilateral Cooperation Portugal–Germany 2024 Joint Call (André Marques)
- 2025: Outgoing Mobility Program, Fundação para a Ciência e a Tecnologia (André Marques)
- 2025: Best Poster Presentation Award, Perspectives in Cardiovascular Biology (PCVB 2025), Frankfurt, Germany (Quélia Ribeiro)
- 2024: “EUTOPIA Ambassador” (André Marques)
- 2024: Best Poster Award, NMS Research Symposium (Catarina Simões)
- 2024: Honorable Mention in the scope of the Bluepharma/University of Coimbra Innovation Award 2023 (Otília Vieira)
- 2023–Present: World’s Top 2% Scientists List (Otília Vieira)
- 2021–Present: World’s Top 2% Scientists List (Winchil Vaz)
- 2024: Travel Grants from the European Study Group on Lysosomal Diseases (Inês Ferreira and Elizeth Lopes)
- 2022: Travel Grant from the “DFG-funded Research Unit FOR2625” (André Marques)
- 2014–2019: FCT Investigator (Consolidator level) (Otília Vieira)
- 2004: Max Planck Postdoctoral Fellowship (Max-Planck-Gesellschaft), Germany (Otília Vieira)
- 2002: Marie Curie Postdoctoral Fellowship (Otília Vieira)
- 2002: EMBO Postdoctoral Fellowship (Otília Vieira)
- Bolsa de Pós-doutoramento da Comissão da União Europeia (Bolsa Marie-Curie), 2002 (Otília Vieira).
- Bolsa da European Molecular Biology Organization (EMBO) de Pós-doutoramento, 2002 (Otília Vieira).
Open Positions
2 PhD Research Opportunities @ Lysosomes and Disease Lab
Colaborations
- Prof. Leo van Grunsven, Department of Biochemistry and Molecular Biology, Vrije Universiteit Brussel, Belgium
- Dr. Agnieszka Rybak-Wolf, Max Delbrück Center and Berlin Institute for Medical Systems Biology (MDC-BIMSB), Germany
- Prof. Rita Grosso, Department of Life Sciences, NOVA FCT, Universidade NOVA de Lisboa, Portugal
- Prof. Bruno Neves, Institute for Research in Biomedicine (iBiMED), University of Aveiro, Portugal
- Prof. Dr. Clare Futter, Department of Cell Biology, University College London – Institute of Ophthalmology, London, United Kingdom
- Prof. Dr. Anthony H. Futerman, Department of Biomolecular Sciences, Weizmann Institute, Israel
- Drs. Jorge Ferreira, Manuel Almeida, and Pedro Gonçalves, Hospital Santa Cruz, Carnaxide, Lisbon, Portugal
- Prof. Dr. Miguel Viana Baptista, Hospital Egas Moniz, Lisbon, Portugal
- Dr. João Paulo Gomes, INSA, Lisbon, Portugal
- Prof. João Conde, NOVA Medical School, Universidade NOVA de Lisboa, Portugal
- Dr. Ricardo Silvestre, ICVS, University of Minho, Braga, Portugal
- Prof. Isabel Soares, Department of Chemistry, University of Coimbra, Portugal
- Prof. Rune Matthiesen, NOVA Medical School, Universidade NOVA de Lisboa, Portugal