Our long-term goal is to unravel the regulatory mechanisms that govern membrane trafficking and understand how their disruption contributes to human disease, toward the discovery of novel therapeutic targets and strategies. To achieve this, we employ state-of-the-art technologies, including live-cell imaging, super-resolution confocal microscopy, and a wide range of molecular biology, biochemistry, and cell biology methodologies.
A central focus of our research is the study of small GTPases of the Rab and Arf families, which belong to the Ras superfamily and are master regulators of all stages of membrane trafficking. Mutations in several of these proteins are associated with human disorders affecting various intracellular organelles, including lysosomes and lysosome-related organelles, such as melanosomes, highlighting their essential roles in cellular homeostasis. In addition, multiple Rab and Arf proteins have been implicated in the progression and invasiveness of several types of cancer.
By elucidating the molecular mechanisms underlying membrane trafficking pathways regulated by Rab and Arf proteins, our research aims to provide a deeper understanding of the fundamental principles of membrane trafficking, shed light on disease etiology, and contribute to the development of innovative therapeutic strategies.
Projects
- NOVA cryoSkin – Natural deep eutectic systems for skin tissue cryopreservation
Ignition Grant for Interdisciplinary Research at NOVA | Fundação Santander
This project is exploring the cryopreservation of NOVA Skin®, a reconstructed human epidermis and skin model that closely mimics human skin architecture and physiology. The main objective is to validate natural deep eutectic systems (NADES) for preserving NOVA Skin® while maintaining post-thawing tissue integrity, cellular viability, and physiological functionality. This validation will demonstrate a sustainable, scalable, and cost-effective solution for skin tissue storage. Ultimately, NOVA CryoSkin aims to develop innovative therapeutic solutions for skin wounds and disorders by enabling the efficient preservation, accessibility, and scalability of the NOVA Skin® model. The successful cryopreservation of NOVA Skin® using NADES can revolutionize skin tissue preservation, reducing logistical complexity and costs, while aligning with sustainability goals. Hence, this project will pave the way for future advances in tissue engineering, regenerative medicine, and biobanking.
- Targeting lysosome exocytosis to impair breast cancer progression and metastasis
Among women, breast cancer (BC) is the predominant type of cancer and the most common cause of cancer-related deaths. In particular, triple negative BC (TNBC) is the most aggressive BC type and the one with the highest mortality. Despite the advances in early detection and adjuvant therapy in recent years, metastasis remains by far the main cause of mortality in these patients. Therefore, the development of novel therapies to impair metastasis is essential to reduce mortality and morbidity. Lysosome exocytosis is an intracellular pathway subverted by cancer cells to enhance cancer cell invasion and progression. Indeed, through lysosome exocytosis, cancer cells secrete hydrolases that degrade the extracellular matrix, enabling angiogenesis, cell migration and invasion. We and others have collected evidence that lysosome exocytosis is upregulated in invasive TNBC cells, suggesting that lysosome exocytosis can be targeted to impair TNBC cell invasion. Therefore, we aim to inhibit lysosome exocytosis as a novel strategy to impair TNBC cell invasion and metastasis. This would represent a major breakthrough as TNBC has the poorest prognosis and the highest morbidity and mortality rates among BC types, which remain refractive to the therapeutic options available.
- Molecular mechanisms of melanin transfer and processing by keratinocytes
In the skin epidermis, melanocytes synthesize the photopigment melanin and transfer it to neighboring keratinocytes. Melanin protects skin cells against ultraviolet (UV) radiation-induced damage, which can lead to the onset of skin cancers. Melanin synthesis occurs in specialized organelles called melanosomes, which share several features with lysosomes and are thus considered lysosome-related organelles. Despite the crucial role of melanin uptake and processing by keratinocytes for skin pigmentation, the pathways involved remain largely unknown. Thus, we are unraveling how keratinocytes process melanin to ensure efficient photoprotection under UV irradiation.
Publications
- Neto MV, Hall MJ, Charneca J, Escrevente C, Seabra MC, Barral DC. Photoprotective Melanin Is Maintained within Keratinocytes in Storage Lysosomes. J Invest Dermatol. 2025 May;145(5):1155-1165.e3. doi: 10.1016/j.jid.2024.08.023.
- Ferreira A, Castanheira P, Escrevente C, Barral DC, Barona T. Membrane trafficking alterations in breast cancer progression. Front Cell Dev Biol. 2024 Mar 12;12:1350097. doi: 10.3389/fcell.2024.1350097.
- Bento-Lopes L, Cabaço LC, Charneca J, Neto MV, Seabra MC, Barral DC. Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing. Int J Mol Sci. 2023 Jul 10;24(14):11289. doi: 10.3390/ijms241411289.
- Cabaço LC, Bento-Lopes L, Neto MV, Ferreira A, Staubli WBL, Ramalho JS, Seabra MC, Barral DC. RAB3A Regulates Melanin Exocytosis and Transfer Induced by Keratinocyte-Conditioned Medium. JID Innov. 2022 Jun 21;2(5):100139. doi: 10.1016/j.xjidi.2022.100139.
- Cabaço LC, Tomás A, Pojo M, Barral DC. The Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness. Front Oncol. 2022 May 10;12:887366. doi: 10.3389/fonc.2022.887366.
- Moreiras H, Bento-Lopes L, Neto MV, Escrevente C, Cabaço LC, Hall MJ, Ramalho JS, Seabra MC, Barral DC. Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease-activated receptor-2 internalization. Traffic. 2022 Jun;23(6):331-345. doi: 10.1111/tra.12843.
- Barral DC, Staiano L, Guimas Almeida C, Cutler DF, Eden ER, Futter CE, Galione A, Marques ARA, Medina DL, Napolitano G, Settembre C, Vieira OV, Aerts JMFG, Atakpa-Adaji P, Bruno G, Capuozzo A, De Leonibus E, Di Malta C, Escrevente C, Esposito A, Grumati P, Hall MJ, Teodoro RO, Lopes SS, Luzio JP, Monfregola J, Montefusco S, Platt FM, Polishchuck R, De Risi M, Sambri I, Soldati C, Seabra MC. Current methods to analyze lysosome morphology, positioning, motility and function. Traffic. 2022 May;23(5):238-269. doi: 10.1111/tra.12839.
- Hall MJ, Lopes-Ventura S, Neto MV, Charneca J, Zoio P, Seabra MC, Oliva A, Barral DC. Reconstructed human pigmented skin/epidermis models achieve epidermal pigmentation through melanocore transfer. Pigment Cell Melanoma Res. 2022 Jul;35(4):425-435. doi: 10.1111/pcmr.13039.
- Escrevente C, Bento-Lopes L, Ramalho JS, Barral DC. Rab11 is required for lysosome exocytosis through the interaction with Rab3a, Sec15 and GRAB. J Cell Sci. 2021 Jun 1;134(11):jcs246694. doi: 10.1242/jcs.246694.
- Moreiras H, Seabra MC, Barral DC. Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms. Int J Mol Sci. 2021 Apr 24;22(9):4466. doi: 10.3390/ijms22094466.
Prizes and Awards
- And Rita Rodrigues - Best poster award, NMS Research Symposium, 6th-7th October 2025
- Cristina Demelas - European Society for Pigment Cell Research (ESPCR) Travel Award (Erlangen, Germany, 25th-27th September 2025)
- Mariana Feliciano - 4th Hospital da Luz Research Congress, 26th May 2025
Colaborations
- Miguel Seabra, NOVA Medical School, NOVA University of Lisbon
- Marta Pojo, Portuguese Institute of Oncology
- Jacinta Serpa, NOVA Medical School, NOVA University of Lisbon and Portuguese Institute of Oncology
- Ana Rita Duarte, Faculty of Sciences and Technology, NOVA University of Lisbon
- Helena Barroso, Egas Moniz School of Health and Science
- Chiara Di Malta, Telethon Institute of Genetics and Medicine, Itália
- Michal Sarna, Jagiellonian University, Polónia
- André Marques, Sea4Us