ANGIOGENESIS
Angiogenesis is the formation of new blood vessels from pre-existing ones and is orchestrated by a variety of pro- and anti-angiogenic signals. Their imbalance, promoting either excessive or insufficient angiogenesis, can lead to disease. Therefore, it is recognized that therapeutic interference with vasculature formation offers a tool for clinical applications.
The main goal of the Angiogenesis Unit is to discover the molecular mechanisms by which angiogenesis is modulated, particularly by subtherapeutic and therapeutic doses of ionizing radiation.
Our findings are crucial to correlate the doses of ionizing radiation with: i) tumor dissemination; ii) colonization of pre-metastatic niches by tumor cells or iii) cardiotoxicity after radiotherapy.
We are also investigating the synergistic interplay between low doses of ionizing radiation and biomaterials/tissue engineering uncovering the underlying mechanisms to open new perspectives on their application in regenerative medicine.
A strong network between bench researchers, physicists and clinicians has been crucial to assure excellence in our work. We are confident about the innovativeness of our research and its clinical applicability.
RESEARCH TEAM
Constantino Rosa Santos , Susana, PhD
GROUP LEADER
Susana Constantino Rosa Santos obtained her degree in Microbial Biology and Genetics from the Faculty of Sciences, University of Lisbon (Portugal), in 1997. She completed her PhD in Bases Fondamentales de l’Oncogénèse at the University of Paris 7 (France) in September 2001. From October 2001 to December 2004, she carried out her postdoctoral research at the Portuguese Institute of Oncology in Lisbon and the Gulbenkian Institute of Science in Oeiras (Portugal). Since 2005, she has been an Assistant Professor at the Lisbon School of Medicine, University of Lisbon. In 2008, she established the Angiogenesis Unit, initially at the Institute of Molecular Medicine (Lisbon), and, since 2014, at CCUL.
ORCID ID: 0000-0002-5711-1292
E-mail: sconstantino@medicina.ulisboa.pt
Oliveira, Paula, PhD
Postdoc Researcher
Paula Alexandra Gomes de Oliveira obtained a degree in Biotechnology Engineering from the Faculty of Engineering, University of Algarve (Portugal) in 2006. She completed her master’s degree in Human Molecular Biology by the Faculty of Sciences, University of Lisbon (Portugal) in 2009 and her PhD at the Lisbon School of Medicine of the Universidade de Lisboa, Portugal, in 2017, in the Angiogenesis Unit, CCUL, under the supervision of Professor Susana Constantino. She is currently a postdoc in the Angiogenesis Unit, CCUL.
ORCID: 0000-0003-1721-9909
E-mail: paulaoliveira@medicina.ulisboa.pt
Vala, Inês Sofia, PhD
Postdoc Researcher
Inês obtained her PhD in Cellular Biology in 2011 while working in the Angiogenesis Unit at the Institute of Molecular Medicine (iMM). From 2006 to 2011, her research focused on the effects of low doses of ionizing radiation (LDIR) on angiogenesis and its potential role in tumour recurrence, invasion, and metastasis, within the clinical context of radiotherapy. During this time, she collaborated closely with the Radiotherapy Service of Hospital de Santa Maria and developed expertise in angiogenesis and radiobiology.
Between 2011 and 2021, Inês worked at the Portuguese National Agency for Scientific and Technological Culture (Ciência Viva), where she promoted scientific literacy. She began as a member of the Education Team, later became Head of Explainers, and ultimately served as Director of the Department of Education, Scientific Programmes, and Events. She was also invited to join the Pedagogical Advisory Board of the Ciência Viva Training Centre, where she continues to serve.
In 2019, she became an Assistant Professor at Lusófona University, teaching in the areas of Biology, Genetics, and Bioethics. Since March 2021, Inês has been a Junior Postdoctoral Researcher at CCUL, conducting translational research on vascular responses to ionizing radiation, with a focus on angiogenesis regulation and its clinical implications in regeneration, tumour progression, and cardiovascular toxicity.
ORCID: 0000-0003-0497-6804
E-mail: ines.oliveira@medicina.ulisboa.pt
Ministro, Augusto, MD, PhD
Researcher
Augusto Manuel Almeida Ministro, obtained his Medical Degree by the Lisbon School of Medicine of the Universidade de Lisboa, Portugal, in 2000. He started his residency at Santa Maria University Hospital – CHULN, E.P.E, Lisbon, in 2003 and became a Vascular Surgery Specialist in 2010. Currently he is a Vascular Surgery Assistant, Kidney Transplant Consultant and unit chief in the Vascular Surgery Department of Santa Maria University Hospital, CHULN E.P.E., Lisbon. He is a member of the CCUL Angiogenesis Unit and completed his PhD in Medicine, Speciality of Vascular Surgery in 2018 (April).
ORCID: 0000-0003-4042-496X
E-mail: augusto.ministro@gmail.com
Co-Researcher in Vascular Biology, Imaging and Surgery
Pereira, Ana Rita, PhD
Postdoc Researcher
Ana Rita Duarte Simões Pereira just finished her PhD (PhD Programme of the Lisbon Academic Medical Centre) at the Angiogenesis Unit. She did her master’s thesis in the Angiogenesis Unit, obtaining her master’s degree in Biochemistry by the Faculty of Sciences of the University of Lisbon in 2014. In 2012, she completed her graduation also in Biochemistry by the Faculty of Sciences and Technology, University of Coimbra. From 2006 to 2008 she completed two years of the degree in Economics in the Faculty of Economics, University of Coimbra.
ORCID: 0000-0002-9057-0781
E-mail: ritasimoespereira@gmail.com
Rocha, Filipe, MSc
PhD Student
Filipe Nunes Rocha graduated in Biology from the Faculty of Science, University of Lisbon (Portugal) in 2017. He obtained his master´s degree in Molecular Biology and Genetics from the Faculty of Science of the University of Lisbon (Portugal), in 2019, and is currently a PhD student (PhD Programme of the Lisbon Academic Medical Center) at the Angiogenesis Unit, CCUL, under the supervision of Susana Constantino.
ORCID: 0000-0002-0095-0052
E-mail: filiperocha@medicina.ulisboa.pt
Simões de Oliveira, Pedro, MD
PhD Student
Pedro Miguel Simões de Oliveira, obtained his Medical Degree from the Faculty of Medicine of the Universitat de Barcelona (Spain) in 2010. He started his residency at Santa Maria University Hospital – CHULN, E.P.E., Lisbon, in 2013 and became a Urology Specialist in 2019. Currently, he is a Urology Assistant, Kidney Transplant Consultant, chief of the Andrology and Infertility section and member of the Reconstructive Urology section in the Urology Department of Santa Maria University Hospital – CHULN, E.P.E., Lisbon.
Currently, he is a PhD student (The PhD Programme of the Lisbon Academic Medical Centre) at the Angiogenesis Unit of CCUL, under the supervision of Prof. Susana Constantino and Prof. Augusto Ministro.
ORCID: 0000-0002-1048-5721
Email: pedrosimoesdeoliveira@gmail.com
Souza, Carolina, BSc
MSc Student
Carolina Rodrigues de Souza graduated with a degree in Molecular and Cellular Biology from NOVA School of Science and Technology, NOVA University Lisbon (Portugal) in 2020. She is currently pursuing a Master’s in Biomedical Research at the Faculty of Medicine, University of Lisbon (Portugal), where she is conducting her thesis at the Angiogenesis Unit, part of the Cardiovascular Centre of the University of Lisbon (CCUL).
Freitas Santos, Maria Teresa
Lab manager
Teresa Santos performed the technical and professional studies of chemistry. She works at the Lisbon School of Medicine of the Universidade de Lisboa, Portugal, since 1986.
E-mail: mtsantos@medicina.ulisboa.pt
COLLABORATORS
An Aerts, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK•CEN), Mol, Belgium
Costanza Emanueli, Imperial College, London
Cristina Barrias, I3S, Porto, Portugal
Elisa Messina, Sapienza University of Rome, Rome
Eugénia Carvalho, CNC-UC, Coimbra, Portugal
Karine Marie Serre, GIMM Care, Lisbon, Portugal
Leonor Saúde, GIMM, Lisboa, Portugal
Luís Mendes Pedro, CCUL, Lisbon, Portugal
Manuela Fiuza, CCUL, Lisbon, Portugal
Marc Mareel, Ghent University Hospital, Ghent, Belgium.
Maria Oliveira, I3S, Porto, Portugal
Pedro Faísca, GIMM, Lisbon, Portugal
Radia Tamarat, Institut de Radioprotection et de Sûreté Nationale (IRSN), Fontenay-aux-Roses, France
ONGOING PROJECTS
As Task Leader:
2017-2021: MEDIRAD: Implications of Medical Low Dose Radiation Exposure (HORIZON2020 NGRP-2016-2017-1)
As Principal Investigator:
2023-2024: ANGIOHEAL: A new view on chronic wound healing treatment: Synergistic interplay between low-dose ionizing radiation and prevascularized dermal spheroids (2022.10387.PTDC)
2018-2021: STRIkINg: Sub-therapeutic doses of ionizing radiation modulate the pre-metastatic niche and induce metastasis. Which are the mechanisms and how to prevent it? (SAICT/FCT/2017/031118)
As Collaborator:
2018-2021: ANGIONICHES: A biomaterial-guided morphogenesis strategy for cell-based therapeutic neovascularization using angiogenic microniches. (POCI/FEDER/FCT/20179)
2018-2021: MAGICIAM: A macrophage immunomodulatory-delivery system to prevent cancer invasion and metastasis (POCI/FEDER/FCT/2017)
SELECTED PUBLICATIONS
Oliveira, P., Vala, I. S., Faísca, P., Guimaraes, J. C., Pina, F., Poli, E., Diegues, I., Osório, H., Matthiesen, R., Serre, K., & Constantino Rosa Santos, S. (2025). Subtherapeutic Dose of Ionizing Radiation Reprograms the Pre-Metastatic Lung Niche, Accelerating Its Formation and Promoting Metastasis. International journal of molecular sciences, 26(13), 6145. URL: https://doi.org/10.3390/ijms26136145. Quartil (Q): Q1.
de Oliveira, P. S., Rocha, F., Vala, I. S., de Oliveira, P., Ministro, A., & Santos, S. C. R. (2023). Urethral Stricture Induction Followed by Buccal Mucosa Graft Urethroplasty in a Rat Model. Journal of visualized experiments : JoVE, (194), 10.3791/65094. URL: https://doi.org/10.3791/65094. Quartil (Q): Q1.
Ribeiro, S., Simões, A. R., Rocha, F., Vala, I. S., Pinto, A. T., Ministro, A., Poli, E., Diegues, I. M., Pina, F., Benadjaoud, M. A., Flamant, S., Tamarat, R., Osório, H., Pais, D., Casal, D., Pinto, F. J., Matthiesen, R., Fiuza, M., & Constantino Rosa Santos, S. (2022). Molecular Changes In Cardiac Tissue As A New Marker To Predict Cardiac Dysfunction Induced By Radiotherapy. Frontiers in oncology, 12, 945521. URL: https://doi.org/10.3389/fonc.2022.945521. Quartil (Q): Q1.
Gil Marques, F., Poli, E., Malaquias, J., Carvalho, T., Portelo, A., Ramires, A., Aldeia, F., Ribeiro, R. M., Vitorino, E., Diegues, I., Costa, L., Coutinho, J., Pina, F., Mareel, M. and Constantino Rosa Santos, S. Low doses of ionizing radiation activate endothelial cells and induce angiogenesis in peritumoral tissues. Radiother Oncol. 2019 Jul 31. pii: S0167-8140(19)32976-7. doi: 10.1016/j.radonc.2019.06.035. URL: http://www.ncbi.nlm.nih.gov/pubmed/31376927. Quartil (Q): Q1.
Marques, F. G., Poli, E., Rino, J., Pinto, M. T., Diegues, I., Pina, F. and Constantino Rosa Santos, S. Low Doses of Ionizing Radiation Enhance the Angiogenic Potential of Adipocyte Conditioned Medium. Radiat Res. 2019 Aug 23. doi: 10.1667/RR15438.1. URL: http://www.ncbi.nlm.nih.gov/pubmed/31442107. Quartil (Q): Q1.
Ministro, A., de Oliveira, P., Nunes, R. J., Dos Santos Rocha, A., Correia, A., Carvalho, T., Rino, J., Faisca, P., Becker, J. D., Goyri-O’Neill, J., Pina, F., Poli, E., Silva-Santos, B., Pinto, F., Mareel, M., Serre, K. and Constantino Rosa Santos, S. Low-dose ionizing radiation induces therapeutic neovascularization in a pre-clinical model of hindlimb ischemia. Cardiovasc Res. 2017 Jun 1;113(7):783-794. doi: 10.1093/cvr/cvx065. URL: http://www.ncbi.nlm.nih.gov/pubmed/28444128. Quartil (Q): Q1.
Pereira, A. R., Mendes, T. F., Ministro, A., Teixeira, M., Filipe, M., Santos, J. M., Barcia, R. N., Goyri-O’Neill, J., Pinto, F., Cruz, P. E., Cruz, H. J. and Constantino Rosa Santos, S. Therapeutic angiogenesis induced by human umbilical cord tissue-derived mesenchymal stromal cells in a murine model of hindlimb ischemia. Stem Cell Res Ther. 2016 Sep 29;7(1):145. doi: 10.1186/s13287-016-0410-4. URL: http://www.ncbi.nlm.nih.gov/pubmed/27680210. Quartil (Q): Q1.
Sofia Vala, I., Martins, L. R., Imaizumi, N., Nunes, R. J., Rino, J., Kuonen, F., Carvalho, L. M., Ruegg, C., Grillo, I. M., Barata, J. T., Mareel, M. and Constantino Rosa Santos, S. Low doses of ionizing radiation promote tumor growth and metastasis by enhancing angiogenesis. PLoS One. 2010 Jun 21;5(6):e11222. doi: 10.1371/journal.pone.0011222. URL: http://www.ncbi.nlm.nih.gov/pubmed/20574535. Quartil (Q): Q1.