CANCER BIOLOGY & EPIGENETICS GROUP

CBEG was established in 2008 and integrates predoctoral and postdoctoral researchers, with diverse academic backgrounds, including Biologists, Biochemists, Pathological, Cytological, and Thanatological Anatomy graduates, and Medical Doctors of several specialties, including Pathologists, Urologists, Gynecologists, Radiologists Hemato-Oncologists, and Medical Oncologists.

In the context of Precision Oncology, we are developing several patient-centered translational research projects addressing tumor biology, pathology, epigenetics, epitranscriptomics, tumor metabolism, and immunology topics.

SCIENTIFIC COORDINATOR

Carmen Jerónimo, PhD
ORCID ID/ Ciência ID: 0000-0003-4186-5345/ CE16-29CB-EDD1
Assistant Researcher
Coordinator TL2 – Cancer/ CI-IPOP@RISE
Scientific Coordinator, Tumor Bank – Department of Pathology
Guest Full Professor at ICBAS-UP
E-mail: carmenjeronimo@ipoporto.min-saude.pt/ cljeronimo@icbas.up.pt

 

TEAM
Senior Researchers

Rui Henrique, MD, PhD
ORCID ID/ Ciência ID: 0000-0003-3171-4666/ 641F-FE09-15E6
Senior Researcher
Senior Consultant Pathologist and Director, Department of Pathology
Guest Full Professor at ICBAS-UP
E-mail: henrique@ipoporto.min-saude.pt/ rmhenrique@icbas.up.pt

Margareta P. Correia, PhD
ORCID ID/ Ciência ID: 0000-0003-4378-0820/ CB11-3261-9D4F
Assistant Researcher
Team Leader of the research topic: Onco-Immuno-Epigenetics
Lecturer in the Master Course in Oncology at ICBAS-UP & Master Course in Molecular Medicine and Oncology at FMUP
Guest Adjunct Professor at ESS.IPP
E-mail: margareta.correia@ipoporto.min-saude.pt

Junior Researchers

Carla Bartosch, MD, PhD
ORCID ID/ Ciência ID: 0000-0003-0646-7667/ 881F-BDAC-46FE
Consultant Pathologist, Department of Pathology
Team Leader of the research topic: Gynecological Tumors
Lecturer in Pathology, Integrated Master in Medicine at ICBAS-UP
E-mail: carla.bartosch@ipoporto.min-saude.pt   

João Lobo, MD, PhD
ORCID ID/ Ciência ID: 0000-0001-6829-1391/ 8A14-8221-1CBF
Attending Pathologist, Department of Pathology
Team Leader of the research topic: Testicular Tumors
Lecturer in Pathology, Integrated Master in Medicine at ICBAS-UP& Lecturer in Biopathology, Integrated Master in Dental Medicine at FMDUP
E-mail: jpedro.lobo@ipoporto.min-saude.pt  

Nair Lopes, PhD
ORCID ID/ Ciência ID: 0000-0003-4732-7361/ F81A-8E25-17DD
E-mail: nair.ribeiro.lopes@ipoporto.min-saude.pt

Vera Miranda-Gonçalves, PhD
ORCID ID/ Ciência ID: 0000-0002-4231-5532/ 8E1B-B722-284F
Lecturer in the Master Course in Oncology at ICBAS-UP & Master Course in Molecular Medicine and Oncology at FMUP
E-mail: vera.miranda.goncalves@ipoporto.min-saude.pt

Guest Researchers

Óscar Rapado González, PhD
ORCID ID/ Ciência ID: 0000-0001-8419-7004/ C019-EAAE-BBB8
Foreigner Researcher – Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
E-mail: oscar.gonzalez@ipoporto.min-saude.pt

Sara Monteiro-Reis, PhD
ORCID ID/ Ciência ID: 0000-0002-2193-2793/ 3014-05F4-935F
Junior Researcher @ Health and Biomechanical Unit-INEGI
Lecturer in the Master Course in Oncology at ICBAS-UP & Master Course in Molecular Medicine and Oncology at FMUP
E-mail: sara.raquel.reis@ipoporto.min-saude.pt/ sreis@inegi.up.pt

Sofia Salta, PhD
ORCID ID/ Ciência ID: 0000-0002-6707-1263/ 6119-2B18-6A26;
E-mail: sofia.salta@ipoporto.min-saude.pt

PhD Students

With External Funding

Supervising
Ana Teixeira-Marques, MSc (in collaboration with i3S/ Centro de investigación Hospital Universitario 12 de Octubre, Espanha; FCT2023.01232.BD);
ORCID ID/Ciência ID: 0000-0003-1396-3466/ 601F-802B-922D;
E-mail: ana.t.marques@ipoporto.min-saude.pt

Catarina Guimarães-Teixeira, MSc (FCT DFA/BD/6038/2020);
ORCID ID/ Ciência ID: 0000-0003-2212-3872/ CE1E-8E02-5ADB;
E-mail: catarina.guimaraes.teixeira@ipoporto.min-saude.pt

Catarina Lourenço, MSc (in collaboration with i3S; FCT2021.06731.BD);
ORCID ID/ Ciência ID: 0000-0003-0644-0202/ 9A1E-2DE0-A004;
E-mail: i37296@ipoporto.min-saude.pt

Filipa Domingues dos Reis, MSc (in collaboration with Leiden University Medical Center, The Netherlands; FCT UI/BD/154816/2023);
ORCID ID/ Ciência ID: 0000-0001-9897-5612/ C014-A6CE-0341;
E-mail: filipa.reis@ipoporto.min-saude.pt

Filipa Moreira Silva, MSc (in collaboration with Bern Univ Hospital, Bern, Switzerland; FCT 2023.00300.BD);
ORCID ID/ Ciência ID: 0000-0002-7272-7300/ 7019-D06D-3E3F;
E-mail: filipa.m.silva@ipoporto.min-saude.pt

Íris da Rocha Carriço, MSc (in collaboration with MFRRP; FCT UI/BD/154815/2023);
ORCID ID/ Ciência ID: 0000-0002-4977-8273/ 3617-1D5C-EE2D;
E-mail: iris.carrico@ipoporto.min-saude.pt

José Pedro Sequeira, MSc (in collaboration with Health Research Institute of Santiago de Compostela-IDIS, Spain; FCT2022.11060.BD);
ORCID ID/ Ciência ID: 0000-0002-4687-3347/ FE1E-E1CF-6983;
E-mail: jose.leite.sequeira@ipoporto.min-saude.pt  

Nuno Tiago Tavares, MSc (in collaboration with the University of California, San Diego, USA; FCT2022.09566.BD);
ORCID ID/ Ciência ID: 0000-0001-8426-1838/ 2718-0ED1-9F74;
E-mail: i38161@ipoporto.min-saude.pt

Vera Constâncio, MSc (in collaboration with Champalimaud Foundation/Beatson Institute, Glasgow, Scotland; LCF/BQ/DR20/11790013);
ORCID ID/ Ciência ID: 0000-0002-3151-0367/ 3116-280A-8462;
E-mail: vera.salvado.constancio@ipoporto.min-saude.pt

Co-Supervising
Diana Montezuma, MD (INESC TEC);
ORCID ID/ Ciência ID: 0000-0001-9551-4589/ 8614-D72D-4861;
E-mail: diana.m.felizardo@ipoporto.min-saude.pt

Mariana Carvalho, MSc (INEGI; FCT2022.09480.BD);
ORCID ID/ Ciência ID: 0000-0001-8620-9718/ 7713-CE2C-47D2;
E-mail: mariana.carvalho@ipoporto.min-saude.pt

Maria Miguel Castro, MSc (i3S; FCT2020.07439.BD);
ORCID ID/ Ciência ID: 0000-0001-5016-2567/ F41B-905E-E21F;
E-mail: mcastro@i3s.up.pt

Mónica Cerqueira, MSc (ICVS; FCT2022.10233.BD);
ORCID ID/ Ciência ID: 0000-0002-8167-4140/ 7D1C-C417-CF6A;
E-mail: monica.cerqueira@ipoporto.min-saude.pt  

Rita Canário, MD (i3S; FCTPD/BD/128001/2016);
ORCID ID/ Ciência ID: 0000-0002-3563-7752/ 4D16-8D65-7129;
E-mail: rita.canario@ipatimup.pt

Sanjana Vig, MSc (REQUIMTE;H2020 MSCA-GA ID: 861138);
ORCID ID/ Ciência ID: 0000-0001-7939-6500/ 911E-5E8D-888C;
E-mail: sanjana@fmd.up.pt

IPO PORTO STAFF

Ana Fernandes Rodrigues, MD;
ORCID ID/ Ciência ID: 0000-0003-2955-055/ 371A-3A6B-696F;
E-mail: ana.fernandes.rodrigues@ipoporto.min-saude.pt

Carlos Ochoa Leite, MD;
ORCID ID/ Ciência ID: 0000-0003-0489-9677/ 7B14-471C-19A5;
E-mail: carlos.ochoa.leite@ipoporto.min-saude.pt

Carina Carvalho-Maia, MSc;
ORCID ID/ Ciência ID: 0000-0002-7011-8341/ B116-C629-89AC;
E-mail: i13035@ipoporto.min-saude.pt

Isaac Braga, MD (in collaboration with CHUP);
ORCID ID/ Ciência ID: 0000-0001-9265-4324/ A31B-745C-57EA;
E-mail: isaac.braga@ipoporto.min-saude.pt

João Carvalho, MD;
ORCID ID/ Ciência ID: 0000-0001-8564-2050/ B318-599E-9623;
E-mail: joao.m.carvalho@ipoporto.min-saude.pt

Lígia Gonçalves, MD;
ORCID ID/ Ciência ID: 0000-0002-5864-8526/ 0D10-301A-79F6;
E-mail: ligiagoncalves@ipoporto.min-saude.pt 

Mónica Pires, MD (CINTESIS@RISE);
ORCID ID/ Ciência ID: 0000-0003-2238-5135/ 451E-BFE8-40BF;
E-mail: monica.pires@ipoporto.min-saude.pt

Rui Freitas, MD;
ORCID ID/ Ciência ID: 0000-0002-4448-6458/ F01F-89CB-26E6;
E-mail: antoniofreitas@ipoporto.min-saude.pt

Rui Silva-Santos, MSc; Pathology Technician
ORCID ID/ Ciência ID: 0000-0002-6392-1785/ 0E14-7605-B96D;
E-mail: rui.silva.santos@ipoporto.min-saude.pt

Sérgio Chacim, MD;
ORCID ID/ Ciência ID: 0000-0002-6316-8789/ A317-C226-0F98;
E-mail: sergio.chacim@ipoporto.min-saude.pt 

Sofia Paulino, MSc; Pathology Technician
ORCID ID/ Ciência ID: 0000-0003-1244-4066/ C31D-B4FF-D098
E-mail: sofia.paulino@ipoporto.min-saude.pt

Research Assistants/Technicians

Ângela Albuquerque-Castro, MSc (LPCC-NRN2024);
ORCID ID/ Ciência ID: 0000-0003-2199-3534/ 921F-34E0-2BEE;
E-mail: angela.castro@ipoporto.min-saude.pt

Cláudia Martins-Lima, PhD (UCIPredict; TRANSCAN3/0001/2021);
ORCID ID/ Ciência ID: 0000-0003-3720-400x/ 8F1D-900A-58F8;
E-mail: claudia.martins.lima@ipoporto.min-saude.pt

Mariana Silva-Ferreira, MSc (PTDC/EME-APL/1342/2020);
ORCID ID/ Ciência ID: 0000-0002-5896-051X/ 521F-556D-5E8E;
E-mail: mariana.ferreira@ipoporto.min-saude.pt

MSc Students

Bárbara Amorim Fernandes, BSc;
ORCID ID/ Ciência ID: 0009-0001-1229-7118/ 9616-BB80-5E6B;
E-mail: barbara.fernandes@ipoporto.min-saude.pt

Diana Inês Machado, BSc;
ORCID ID/ Ciência ID: 0009-0006-4466-533X/ 7A12-0002-3E48;
E-mail: diana.machado@ipoporto.min-saude.pt

Fernanda Fernandes-Pontes, BSc;
ORCID ID/ Ciência ID: 0009-0007-3931-0443/ 1C19-894E-FD30;
E-mail: fernanda.pontes@ipoporto.min-saude.pt

Mariana Cantante, BSc;
ORCID ID/ Ciência ID: 0009-0009-0221-4006/ 931E-836A-842F;
E-mail: mferreira@ipoporto.min-saude.pt

Mariana Lima-Costa, BSc;
ORCID ID/ Ciência ID: 0009-0001-3257-3693/ 261D-7564-4CD4;
E-mail: mariana.l.costa@ipoporto.min-saude.pt

Marta Rodrigues, BSc;
ORCID ID/ Ciência ID: 0009-0009-1444-102X/ 271C-2BE4-CAA2;
E-mail: marta.l.rodrigues@ipoporto.min-saude.pt

Patrícia Ferreira-Torre, BSc;
ORCID ID/ Ciência ID: 0009-0003-7143-4543/ 2517-866A-C5B6;
E-mail: patricia.torre@ipoporto.min-saude.pt

Rúben Oliveira-Sousa, BSc (em colaboração com GFMRPR)
ORCID ID/ Ciência ID: 0000-0002-0776-5212/ 2310-F2F9-4178;
E-mail: ruben.d.sousa@ipoporto.min-saude.pt

Rui Ribeiro-Pereira, BSc;
ORCID ID/ Ciência ID: 0009-0009-4191-9797/ 3218-FC13-315D;
E-mail: rui.pereira@ipoporto.min-saude.pt

Other collaborators

Ana Isabel Varelas, MSc; Attending Pathologist
Ana Luísa Cunha, MD; Consultant Pathologist
Ana Teresa Martins, MSc; Pathology Technician
Andreia Coutada, MSc; Resident in Pathology
Ângelo Rodrigues, MD; Consultant Pathologist
Carla Renata Dias, MD; Consultant Pathologist
Davide Gigliano, MD; Attending Pathologist
Fernanda Silva, BSc; Pathology Technician
Isa Carneiro, MSc; Pathology Technician
Jorge Torres-Ferreira, MSc; Pathology Technician
Júlia Azevedo, MD; Resident in Pathology
Leonardo Moço, MD; Clinical Hematologist Resident
Maria Alzamora; MD; Resident in Pathology
Nuno Coimbra, MD; Consultant Pathologist
Paula Dias, BSc; Pathology Technician
Paula Lopes, BSc; Pathology Technician
Paula Monteiro, MD; Consultant Pathologist
Renata Vieira, BSc; Pathology Technician
Rita Guimarães, MSc; Pathology Technician
Sara Cardoso MSc; Clinical Pathology Technician
Sérgio Lopes, PhD; Cell Therapy Clinical Biologist
Tiago Ramos, MD; Radioncologist
Verónica Ferreira, BSc; Pathology Technician

Aims

The core aim of our group is to portray in depth epigenetic/ epitranscriptomic mechanisms involved in carcinogenesis, which might be used as clinical tools for early detection, diagnosis, prognostication, and therapy prediction. The investigation of the mechanism and role of epigenetic-modulating drugs (epi-drugs) is another major goal. Moreover, owing to the relevance that Immuno-oncology has demonstrated in recent years, we are also exploring the epigenetic modulation of biomolecules involved in immune responses, aiming at the improvement of immunotherapeutic strategies.

PROJECTS WITH EXTERNAL FUNDING

International
MindGaP- “Bridging the gap between Mind, Brain and Body: Exosome role and monitoring” IN COLLABORATION with UCoimbra, School of Engineering of IPP and European universities (LINU, VTT, and UOULU); Funding agency: H2020-FETOPEN, Budget: 799K€ (2019-2024) (PI@IPO Porto: Prof. Rui Henrique; Co-PI/WP leader: Prof. Carmen Jerónimo). In collaboration with Psycho-oncology Service and Breast Clinic.

MindGAP looks for sensitive health indicators among exosomes that circulate throughout the body and that may change under disease. To this end, the possibility of using MINDFULNESS meditation as a mind-related tool to control the cargo of exosomes is explored. If meditation is successful in changing the behavior and attitudes of many people, it means that the exosomes cargo may be changed through this process. The obtained knowledge aims at opening doors to an innovative device that may be used by everyone to understand his/her health status.

Publications

Monteiro-Reis S, Carvalho-Maia C, Bart G, Vainio SJ, Pedro J, Silva ER, Sales G, Henrique R, Jerónimo C. Secreted Extracellular Vesicle Molecular Cargo as a Novel Liquid Biopsy Diagnostics of Central Nervous System Diseases. Int J Mol Sci. 22(6):3267, 2021. doi: 10.3390/ijms22063267.

Pedro J, Monteiro-Reis S, Carvalho-Maia C, Henrique R, Jerónimo C, Silva ER. Evidence of psychological and biological effects of structured Mindfulness-Based Interventions for cancer patients and survivors: A meta-review. Psychooncology. 30(11):1836-1848, 2021. doi: 10.1002/pon.5771.

Pereira DR, Silva ER, Carvalho-Maia C, Monteiro-Reis S, Lourenço C, Calisto R, Teixeira RJ, Carlson LE, Bart G, Vainio SJ, Sales MGF, Jerónimo C, Henrique R. The modulatory role of internet-supported mindfulness-based cognitive therapy on extracellular vesicles and psychological distress in people who have had cancer: a protocol for a two-armed randomized controlled study. Trials. 23(1):118, 2022. doi: 10.1186/s13063-022-06045-x

UCIPredict- “UCIPredict: Circulating tumour microenvironment components as Urothelial Cancer Immunotherapy Response Predictors” IN COLLABORATION with CIEMAT (Spain); Funding agency: TRANSCAN-3, ERA-NET, Sustained collaboration of national and regional programmes in cancer research (JTC 2021) co-funded by the European Commission/DG Research and Innovation; Budget: 99K€ (2023-2025) [PI@IPO Porto: Prof. Carmen Jerónimo, Coordinator: Dr. Marta Dueñas (CIBER, SP)]

UCIPredict will develop an innovative and reliable urine and blood-based biomarker test for response prediction to immunotherapy IT and tumour recurrence, using non-invasive techniques measuring circulating biomarkers from tumour and tumour microenvironment. Implementation of liquid biopsy biomarkers will improve diagnosis, prognosis and prediction of IT response in UC patients. The main objective of this project is to identify molecular and cellular signatures from urine and blood samples to develop a robust and reproducible laboratory tool for personalized therapy and IT response prediction in UC patients. We will 1) Identify potential molecular targets to guide IT treatments in UC, 2) Detect circulating tumour cells (CTCs) and tumour hybrid cells (THCs) in IT treated and metastatic patients and 3) Evaluate immunomodulation for IT outcome.

CCI4EU “Comprehensive Cancer Infrastructures for the European Union” Funding agency: 4 EUROPE- HORIZON-MISS-2022-CANCER-01-02-101103746; Budget: 57K€ (2023-2026) [PI@IPO Porto: Prof. Rui Henrique, Coordinators: Carla Finocchiaro, Valentina Lungheu and Maurizio Cicero – Organisation of European Cancer Institutes (OECI-EEIG)]

The aim of the CCI4EU consortium is to strengthen the research capacities of Comprehensive Cancer Infrastructures, by: defining CCI maturity model; designing tailored Capacity Building Programme interventions; delivering online training courses; implementing targeted onsite interventions; disseminate, exploit and report results.

PROSTAMET – “PROSTAMET A Comprehensive Translational Research and Training Pipeline Harnessing Lipid Metabolism to Improve Prostate Cancer Management and Educate Young Researchers in Tackling Complex Disease” Funding agency: European Commission HORIZON-MSCA-2022-DN-01 (Grant agreement ID: 101120283), Budget: 243K€ (2024-2027) [PI@IPO Porto: Prof. Carmen Jerónimo, Coordinator: Prof. Johannes Swinnen (KU Leuven, BE)].

In the face of complex multifactorial diseases, such as cancer, and the challenges posed by our aging society, the translation of technological advancements into personalised and cost-effective treatments remains a pressing concern for the scientific community. With the support of the Marie Skłodowska-Curie Actions, the PROSTAMET project will create an immersive Doctoral Network (DN) dedicated to training the next generation of researchers in tackling these types of diseases. With a focus on prostate cancer, the project aims to bridge the gaps in translational research by exploring the untapped potential of altered lipid metabolism. By harnessing a transdisciplinary mindset and education, the project aims to establish a unique lipid-focused research pipeline.

National

ONGOING

EpImmunePCa – “On the crossroads of Immuno-Epigenetics for targeting advanced Prostate Cancer” IN COLLABORATION with INEB/i3S, Funding agency: Fundação para a Ciência e Tecnologia (Technology and Science Foundation) (2022.04809.PTDC), Budget: 250K€ (2023-2025) (PI: Dr. Margareta Correia, Co-PI-Prof. Rui Henrique).

The overall objective of this project is to define a transcriptional and epigenetic profile of cytotoxic tumor-infiltrating lymphocytes, which can be targeted to increase the efficacy of immunotherapies, especially in metastatic castration-resistant prostate cancer (mCRPC), with the translational aim of combining epi-drug pre-conditioning and adoptive cell transfer targeting PCa tumor-associated molecules.

PCaEVision- “Decoding the role of extracellular vesicles in prostate cancer bone metastasis” IN COLLABORATION with Champalimaud Foundation and CNIO (Spain), Funding agency: Fundação para a Ciência e Tecnologia (Technology and Science Foundation) (2022.05135.PTDC), Budget: 50K€ (2023-2024) (PI: Dr. Vera Constâncio, Co-PI-Dr. Hector Peinado).

The overarching aim of PCaEVision is to foster the knowledge of physiopathological processes in PCa bone metastasis development by tackling the contribution of PCa derived extracellular vesicles (EVs) for bone metastasis development in vivo.It is expected that PCaEVision will contribute with: i) the elucidation of the role of EVs produced by PCa primary tumors in bone metastatic disease development, opening a venue for future studies aiming to characterize the molecular alterations caused by PCa derived EVs during bone metastasis initiation and progression, and ii) the identification of new potential biomarkers of PCa aggressive disease. Ultimately these findings could contribute to the improvement of health and survival of PCa cancer patients.

CONCLUDED

EpiMarkGermCell – “Development of novel prognostic and predictive epigenetic biomarkers for malignant testicular germ cell tumors”Funding agency: Fundação para a Ciência e Tecnologia (FCT; Technology and Science Foundation) (POCI-01-0145-FEDER-29043); Budget: 240K€ (2018-2021) (PI: Prof. Rui Henrique, MD PhD, Co-PI: Prof. Carmen Jerónimo, PhD).

The overall objective of this project is to discover and validate novel prognostic and predictive epigenetic-based biomarkers for TGCT, allowing for the delivery of improved patient care. Tissue and liquid biopsies will be made available and tested for altered DNA methylation patterns, modifying/chromatin remodelling enzymes expression and miRNAs transcript levels. Successful candidate biomarkers will be submitted for European patenting. This project builds on the experience of Cancer Biology and Epigenetics Group from IPO Porto in developing epigenetic-based biomarkers for urological cancers.

Publications

Lobo J, Constâncio V, Leite-Silva P, Guimaraes R, Cantante M, Braga I, Mauricio J, Looijenga LHJ, Henrique R, and Jerónimo C, Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples. Clin Epigenetics, 2021. 13(1): p. 70.DOI: 10.1186/s13148-021-01048-y.

Lobo J, Constâncio V, Guimaraes-Teixeira C, Leite-Silva P, Miranda-Goncalves V, Sequeira JP, Pistoni L, Guimarães R, Cantante M, Braga I, Mauricio J, Looijenga LHJ, Henrique R, and Jerónimo C, Promoter methylation of DNA homologous recombination genes is predictive of the responsiveness to PARP inhibitor treatment in testicular germ cell tumors. Mol Oncol, 2021. 15(4): p. 846-865.DOI: 10.1002/1878-0261.12909.

Lobo J, Cardoso AR, Miranda-Goncalves V, Looijenga LHJ, Lopez M, Arimondo PB, Henrique R, and Jeronimo C, Targeting Germ Cell Tumors with the Newly Synthesized Flavanone-Derived Compound MLo1302 Efficiently Reduces Tumor Cell Viability and Induces Apoptosis and Cell Cycle Arrest. Pharmaceutics, 2021. 13(1).DOI: 10.3390/pharmaceutics13010073.

Lobo J, Guimaraes-Teixeira C, Barros-Silva D, Miranda-Goncalves V, Camilo V, Guimaraes R, Cantante M, Braga I, Mauricio J, Oing C, Honecker F, Nettersheim D, Looijenga LH, Henrique R, and Jeronimo C, Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors. Cancers (Basel), 2020. 12(10).DOI: 10.3390/cancers12102903.

Lobo J, Guimaraes R, Miranda-Goncalves V, Monteiro-Reis S, Cantante M, Antunes L, Braga I, Mauricio J, Looijenga LH, Jeronimo C, and Henrique R, Differential expression of DNA methyltransferases and demethylases among the various testicular germ cell tumor subtypes. Epigenomics, 2020. 12(18): p. 1579-1592.DOI: 10.2217/epi-2020-0066.

Lobo J, Alzamora MA, Guimaraes R, Cantante M, Lopes P, Braga I, Mauricio J, Jeronimo C, and Henrique R, p53 and MDM2 expression in primary and metastatic testicular germ cell tumors: Association with clinical outcome. Andrology, 2020. 8(5): p. 1233-1242.DOI: 10.1111/andr.12814.

Fontes-Sousa M, Lobo J, Magalhaes H, Cassis J, Malheiro M, Ramos S, Henrique R, Martins A, and Mauricio MJ, Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification. BMC Urol, 2020. 20(1): p. 127.DOI: 10.1186/s12894-020-00682-7.

Lobo J, Gillis AJM, van den Berg A, Dorssers LCJ, Belge G, Dieckmann KP, Roest HP, van der Laan LJW, Gietema J, Hamilton RJ, Jeronimo C, Henrique R, Salvatori D, and Looijenga LHJ, Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers: Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data. Cells, 2019. 8(12).DOI: 10.3390/cells8121637.

Lobo J, Rodrigues A, Guimaraes R, Cantante M, Lopes P, Mauricio J, Oliveira J, Jeronimo C, and Henrique R, Detailed Characterization of Immune Cell Infiltrate and Expression of Immune Checkpoint Molecules PD-L1/CTLA-4 and MMR Proteins in Testicular Germ Cell Tumors Disclose Novel Disease Biomarkers. Cancers (Basel), 2019. 11(10).DOI: 10.3390/cancers11101535.

Lobo J, Nunes SP, Gillis AJM, Barros-Silva D, Miranda-Goncalves V, Berg AVD, Cantante M, Guimaraes R, Henrique R, Jeronimo C, and Looijenga LHJ.,  XIST-Promoter Demethylation as Tissue Biomarker for Testicular Germ Cell Tumors and Spermatogenesis Quality. Cancers (Basel), 2019. 11(9).DOI: 10.3390/cancers11091385.

Lobo J, Pinto C, Pinheiro M, Lobo F, Sousa N, Lopes P, Looijenga LH, Jeronimo C, Teixeira MR, and Henrique R, Widening the spectrum of Lynch syndrome: first report of testicular seminoma attributable to MSH2 loss. Histopathology, 2020. 76(3): p. 486-489.DOI: 10.1111/his.13979.

Lobo J, Costa AL, Cantante M, Guimaraes R, Lopes P, Antunes L, Braga I, Oliveira J, Pelizzola M, Henrique R, and Jeronimo C, m(6)A RNA modification and its writer/reader VIRMA/YTHDF3 in testicular germ cell tumors: a role in seminoma phenotype maintenance. J Transl Med, 2019. 17(1): p. 79.DOI: 10.1186/s12967-019-1837-z.

Costa AL, Moreira-Barbosa C, Lobo J, Vilela-Salgueiro B, Cantante M, Guimaraes, R., Lopes P, Braga I, Oliveira J, Antunes L, Henrique R, and Jeronimo C,  DNA methylation profiling as a tool for testicular germ cell tumors subtyping. Epigenomics, 2018. 10(12): p. 1511-1523.DOI: 10.2217/epi-2018-0034.

Lobo J, Costa AL, Vilela-Salgueiro B, Rodrigues A, Guimaraes R, Cantante M, Lopes P, Antunes L, Jeronimo C, and Henrique R, Testicular germ cell tumors: revisiting a series in light of the new WHO classification and AJCC staging systems, focusing on challenges for pathologists. Hum Pathol, 2018. 82: p. 113-124.DOI: 10.1016/j.humpath.2018.07.016.

Vilela-Salgueiro B, Barros-Silva D, Lobo J, Costa AL, Guimaraes R, Cantante M, Lopes P, Braga I, Oliveira J, Henrique R, and Jeronimo C, Germ cell tumour subtypes display differential expression of microRNA371a-3p. Philos Trans R Soc Lond B Biol Sci, 2018. 373(1748).DOI: 10.1098/rstb.2017.0338.

HyTherCaP – “Hydralazine: Testing an off-label effect in Castration-Resistant Prostate Cancer” Funding agency: Fundação para a Ciência e Tecnologia (FCT; Technology and Science Foundation) (POCI-01-0145-FEDER-29030); Budget: 240K€ (2018-2021); (PI: Prof. Carmen Jerónimo, PhD, Co-PI@UA: Prof. João F Mano, PhD).

The overall objective of this project is to confirm hydralazine’s mechanism of action in CRPC, which putatively involves demethylation-mediated AR re-expression and define a biomarker predictive of response to this therapy, enabling the off-label use of hydralazine in CRPC patient subset displaying AR hypermethylation.

Publications

Antunes J, Gaspar VM, Ferreira L, Monteiro M, Henrique R, Jeronimo C, and Mano JF, In-air production of 3D co-culture tumor spheroid hydrogels for expedited drug screening. Acta Biomater, 2019. 94: p. 392-409.DOI: 10.1016/j.actbio.2019.06.012.

Marques-Magalhães Â, Graça I, Miranda-Gonçalves V, Henrique R, Lopez M, Arimondo PB, Jerónimo C. Anti-neoplastic and demethylating activity of a newly synthetized flavanone-derived compound in Renal Cell Carcinoma cell lines. Biomed Pharmacother. 141:111681, 2021. doi: 10.1016/j.biopha.2021.111681. 

Pacheco MB, Camilo V, Lopes N, Moreira-Silva F, Correia MP, Henrique R, Jerónimo C. Hydralazine and Panobinostat Attenuate Malignant Properties of Prostate Cancer Cell Lines. Pharmaceuticals (Basel). 14(7):670, 2021. doi: 10.3390/ph14070670.

Lopes N, Pacheco MB, Soares-Fernandes D, Correia MP, Camilo V, Henrique R, Jerónimo C. Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer. Biomedicines 9(8):976, 2021. doi: 10.3390/biomedicines9080976.

Moreira-Silva F, Outeiro-Pinho G, Lobo J, Guimarães R, Gaspar VM, Mano JF, Agirre X, Pineda-Lucena A, Prosper F, Paramio JM, Henrique R, Correia MP, Jerónimo C. G9a inhibition by CM-272: Developing a novel anti-tumoral strategy for castration-resistant prostate cancer using 2D and 3D in vitro models. Biomed Pharmacother. 150:113031, 2022. doi: 10.1016/j.biopha.2022.113031.

NASYTHOR – “Novel Natural and Synthetic Compounds for Treating Hormone Resistant Tumors” Funding Agency: Fundação para a Ciência e Tecnologia (FCT; Technology and Science Foundation)  (NORTE-01-0145-FEDER-024156); Budget: 150K€ (2017-2019); PI: Regina Silva, PhD, Co-IP@IPO Porto: Carmen Jerónimo, PhD.

This project aims to evaluate the antitumor potential of plant extracts, ionic liquids and quinoxalines in hormone-resistant tumors common in the Northern region of Portugal, in this case castration-resistant prostate tumors and estrogen-independent breast tumors. The project involves the in vitro evaluation of the antitumor potential in prostate and breast cell lines in order to select the most promising ones and in vivo using zebrafish as a model, the identification of gene expression by treatment with the selected compounds in order to infer the molecular mechanism of action underlying the cytotoxic effects and the evaluation of the clinical utility of gene expression that can be used to predict therapeutic response and thus serve as a biomarker for clinical management and therapeutic guidance. With this approach, it is expected to identify new anti-tumor compounds targeting the most common and incident tumors in the Northern Region of Portugal.

Publications

Vieira FQ, Marques-Magalhães Â, Miranda-Gonçalves V, Ferraz R, Vieira M, Prudêncio C, Jerónimo C*, Silva RA*. The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines.Int J Mol Sci. 21(24):E9584, 2020. doi: 10.3390/ijms21249584.

TRIMARKCHIP – “Assessing the trifecta of cancer circulating biomarkers: a combined microfluidics platform for detection of CTCs, exosomes and ctDNA” Funding agency: Fundação para a Ciência e Tecnologia (FCT: Technology and Science Foundation) (POCI-01-0145-FEDER-030831- PTDC/BTM-TEC/30831/2017), Budget: 41K€ (2018-2022) PI@i3S: Fernando J Monteiro, PhD, Co-PI: Carmen Jerónimo, PhD.

The proposed project focuses on developing an advanced microfluidics one-chip system for isolation and characterization of three circulating biomarkers present in peripheral blood of cancer patients: Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes. This advanced system will be applied for lung cancer diagnosis, prognosis, assist in treatment selection, and assess cells response to therapy. Lung cancer continues to be the deadliest cancer worldwide, difficult to detect at early stages and in many cases, inaccessible for tissue biopsy. New strategies are needed for early detection of the primary tumor and metastases and correct selection of patient-specific treatments depending on tumor mutations. This system would be a thorough and powerful tool to assess, from a simple blood draw, the complete genetic landscape of the disease, from the primary site to possible metastases, assisting in a continuous, real-time, monitoring of each patient disease.

Publications

Carvalho Â, Guimarães-Teixeira C, Constâncio V, Fernandes M, Macedo-Silva C, Henrique R, Monteiro FJ, Jerónimo C. One sample fits all: a microfluidic-assisted methodology for label-free isolation of CTCs with downstream methylation analysis of cfDNA in lung cancer. Biomater Sci. 10(12):3296-3308, 2022. doi: 10.1039/d2bm00044j.

R&D CONTRACTS WITH PHARMA

KYMAB – “Immunoprofiling characterisation of clinical samples by IHC and gene expression analysis and correlation with clinical outcomes in support of translational medicine strategies for ICOS and PD-L1-IC antibody therapeutics” Kymab Ltd. (Cambridge, UK); Funding: 159K€ (2019-2022) (PI: Rui Henrique, PhD).

This project aims to support translational medicine employment, from early discovery to clinical development, via the strengthening of the understanding of target expression in clinically relevant human samples and correlation with clinical features of disease and outcome.

Collaborators in Competitive Funded projects:

• CyclicCell: PTDC/EME-APL/1342/2020
• GLYCOTARGET: PTDC/MEC-ONC/0491/2021
• PRIME-ROSE- Precision Cancer Medicine Repurposing System using pragmatic Trials- HORIZON-RIA- 101104269
• ACCuseD: PTDC/SAU-SER/30388/2017

PROJECTS WITH INTERNAL FUNDING

DNAmeCERVIX- “DNA methylation biomarkers for triage of hrHPV positive cases in the Northern Portugal population-based cervical cancer screening program” funded by the Research Centre of Portuguese Oncology Institute (PI 142-CI-IPOP-130-2020), Budget: 40K€ (2020-2024) (PI: Prof. Carmen Jerónimo; Co-PI: Prof. Rui Henrique). In collaboration with ARS-Norte.

HPV-based screening strategies attain high throughput due to automation and display high sensitivity, compared to cytology, but they lack specificity, especially among young women, due to the high prevalence of transient infections. Nonetheless, DNA methylation has shown promise as a triage marker for referral to colposcopy of HR-HPV-positive women, disclosing higher sensitivity than cytology in this setting. The main aim of this project is to validate a panel of DNA methylation-based markers as a triage test for women with HR-HPV positive testing in the context of population-based cervical cancer screening.

Publications

Salta S, Maia-Moço L, Estevão-Pereira H, Sequeira JP, Vieira R, Bartosch C, Petronilho S, Monteiro P, Sousa A, Baldaque I, Rodrigues J, Sousa H, Tavares F, Henrique R, Jerónimo C. Performance of DNA methylation-based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study. Int J Cancer, 149(11):1916-1925, 2021. doi: 10.1002/ijc.33778.

Salta S, Lobo J, Magalhães B, Henrique R, Jerónimo C. DNA methylation as a triage marker for colposcopy referral in HPV-based cervical cancer screening: a systematic review and meta-analysis. Clin Epigenetics, 15: 125, 2023. doi: 10.1186/s13148-023-01537-2

Salta S, Sequeira JP, Lobo J, Sousa A, Sousa H, Baldaque I, Monteiro P, Tavares F, Henrique R, Jerónimo C. Preliminary outcomes of the Cervical Cancer Screening Program of Northern Portugal: a snapshot. J Infect Public Health, 17(6):1057-1064, 2024. doi: 10.1016/j.jiph.2024.04.020

EpiPaRTy – “Advances in Epigenetic targeting for PCa: Dissecting the interplay between ncRNAs and chromatin remodelers and their role as biomarkers of RadioTherapy resistance” (PI-159-CI-IPOP-152-2022), Budget: 35K€ (2021-2024) (PI: Prof. Carmen Jerónimo)

Despite the high survival rates, some prostate cancer (PCa) tumors acquire an aggressive phenotype and might disseminate, becoming resistant to therapy, as the external beam radiation therapy, which is proven to have decreased effectiveness in more advanced stages, with the appearance of biochemical recurrences or metastization. According to cell death challenge in radiation-based therapy, epigenetic alterations, including non-coding RNAs and chromatin remodelling modifications deregulation, affect the expression of several critical target genes related to the cell growth, DNA damage repair and cell cycle deregulation. Thus, herein we aim to discover novelty therapeutic strategies against major epigenetic players that might reverse radioresistant PCa phenotype, as well as, unveiling novel prognostic and predictive biomarkers with a clinical value in PCa patient stratification.

Publications

Macedo-Silva C, Benedetti R, Ciardiello F, Cappabianca S, Jerónimo C, Altucci L. Epigenetic mechanisms underlying prostate cancer radioresistance. Clin Epigenetics. 13(1):125, 2021. doi: 10.1186/s13148-021-01111-8.

Macedo-Silva C, Miranda-Gonçalves V, Tavares NT, Barros-Silva D, Lencart J, Lobo J, Oliveira Â, Correia MP, Altucci L, Jerónimo C. Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling. Signal Transduct Target Ther. 8(1):395. doi: 10.1038/s41392-023-01639-6.

DECODE – “Epigenetic regulation of non-coding RNAs in Prostate Cancer” (PI 157-CI-IPOP-121-2019), Budget: 35K€ (2021-2024). (PI: Prof. Carmen Jerónimo)

Decoding PCa aims to provide further insights into basic medicine and how non-coding RNA chemical alterations can be translated into the clinical practice. The specific regulatory mechanisms through which epitrancriptomics can inhibit or promote cancer onset and progression depends essential on 2 aspects: (1) whether the chemical modifications target oncogenes or tumor suppressor RNAs; (2) changes in the expression or activity of the molecules responsible for install/remove the modifications. Therefore, clarifying epitranscriptomic target genes and related pathways is mandatory to understand the mechanistic impact of RNA modifications in cancer biology. We aim to tackle whether unveiled RNA methylation profiles may be helpful to clarify the mechanisms behind prostate cancer and to improve clinical decisions and existing therapies.

Publications

Barros-Silva D, Lobo J, Guimarães-Teixeira C, Carneiro I, Oliveira J, Martens-Uzunova ES, Henrique R, Jerónimo C. VIRMA-Dependent N6-Methyladenosine Modifications Regulate the Expression of Long Non-Coding RNAs CCAT1 and CCAT2 in Prostate Cancer. Cancers 12(4): E771, 2020. doi: 10.3390/cancers12040771.

Barros-Silva D, Tsui J, Jerónimo C, Jenster G, Martens-Uzunova ES. Site-specific analysis of ribosomal 2’O-methylation by quantitative reverse transcription PCR under low deoxynucleotide triphosphate concentrations. Biotechniques. 74(5):225-235, 2023. doi: 10.2144/btn-2022-0122.

MiRVeBlad- “Identification of Exosomal-derived miRNAs as non-invasive high-risk BlCa biomarkers” (PI-160-CI-IPOP-153-2021), Budget: 35K€ (2021-2024). (PI: Prof. Carmen Jerónimo, Prof. Rui Henrique) This project has been developed within the frame of Porto.CCC

Extracellular vesicles (EVs) have an essential functional role in local tumor progression, metastatic spread, and emergence of drug resistance in different types of cancer. As such, EVs are being explored as potential diagnostic, prognostic, and predictive markers of malignancy. Virtually all biomolecules (such as DNA, RNA, ncRNA or proteins) present within EVs can be tested. In the setting of urothelial tumors, there is recent evidence suggesting that EVs reflect the molecular signature of the primary tumor cells and can, therefore, serve as an effective tool for molecular characterization of tumors themselves as well as to uncover clinical useful biomarkers We aim to discover and validate these biomarkers in liquid biopsies from patients with urothelial tumors. Effective biomarkers will allow us to diagnose tumors at early stages and to adequately stratify low- and high-risk lesions.

Publications

Teixeira-Marques A, Lourenço C, Oliveira MC, Henrique R, Jerónimo C. Extracellular Vesicles as Potential Bladder Cancer Biomarkers: Take It or Leave It? Int J Mol Sci. 24(7):6757, 2023. doi: 10.3390/ijms24076757. PMID: 37047731; PMCID: PMC10094914.

Montezuma D, Teixeira-Marques A, Jerónimo C, Henrique R. Epigenetic extracellular vesicle-based biomarkers for urological malignancies: is the hope worth the hype? Epigenomics. 13(19):1514-1521, 2021. doi: 10.2217/epi-2021-0333. PMID: 34617453.

Teixeira-Marques A, Monteiro-Reis S, Montezuma D, Lourenço C, Oliveira MC, Constâncio V, Sequeira JP, Carvalho-Maia C, Freitas R, Martens-Uzunova ES, Vasconcelos MH, Henrique R, Jerónimo C. Improved recovery of urinary small extracellular vesicles by differential ultracentrifugation Sci Reports (accepted).

PCaEXOBone – “Prostate Cancer pre-metastatic niche formation: Exosomal osteotropism” (PI 158-CI-IPOP-151-2021), Budget: 45K€ (2021-2024). (PI: Prof. Carmen Jerónimo)

Prostate cancer (PCa) is a major public health concern worldwide. Despite the high incidence, PCa-related deaths are mostly due to metastatic disease, for which no curative treatments are available. Although bone metastasis represents up to 84% of all PCa metastasis, the mechanisms underlying PCa osteotropism remain largely unknown.

Exosomes can transfer their cargo, functionally impacting recipient cells. Thus, exosomes have been linked with the formation of pre-metastatic niches by creating a distant pro-tumour environment. Moreover, although exosomes have been associated with metastatic organ tropism in several cancer types, exosomal signatures and their biological relevance in PCa carcinogenesis and metastization are still poorly understood. Therefore, we aim to unravel the function of PCa derived exosomes in bone metastasis development and identify exosomal cargo contributing to osteotropism. Additionally, we intend to develop a specific prognostic tool of bone pre-metastatic niche formation able to predict the likelihood of progression to metastatic disease.

EpiMetaboK – “Epitranscriptomic alterations within renal cancer metabolism reprogramming: uncovering new therapeutic targets” (PI 112-CI-IPOP-92-2018), Budget: 50K€ (2022-2024) (PI: Prof. Carmen Jerónimo; Co-PI Dr. Vera Miranda-Gonçalves)

Renal cell carcinoma (RCC) is the most common neoplasm affecting the kidney. Current therapies are mostly curative for localized disease, but do not completely preclude recurrence and metastization. There is an unmet need for biomarkers that may accurately discriminate patient that are effectively cured by surgery alone from those which will eventually relapse and develop metastatic disease. In this vein, improved understanding of the biology of RCC progression and metastization is imperative. Epitranscriptomic is a new layer of gene expression regulation at RNA level. Presently, metabolic reprogramming is considered a cancer hallmark, and its interplay with epigenetics has been addressed by several research teams, contrarily to interactions with epitranscriptomics, whose implications in RCC are still mostly unknown. Hence, this project aims to investigate the role of epitranscriptomic modulation in RCC and, specifically, to uncover which metabolic enzymes are regulated by m6A.

Publications:

Guimarães-Teixeira C, Barros-Silva D, Lobo J, Soares-Fernandes D, Constâncio V, Leite-Silva P, Silva-Santos R, Braga I, Henrique R, Miranda-Gonçalves V, Jerónimo C. Deregulation of N6-Methyladenosine RNA Modification and Its Erasers FTO/ALKBH5 among the Main Renal Cell Tumor Subtypes. J Pers Med. 11(10):996, 2021. doi: 10.3390/jpm11100996.

MethyProCancer – “Prostate Cancer Risk Stratification and monitoring approach: Unveiling circulating DNA methylation-based biomarkers” (PI189-CI-IPOP-22-2023), Budget: 25K€ (2023-2024) (PI: Prof. Carmen Jerónimo; Co-PI Prof. Rui Henrique)

Although most prostate cancers (PCa) are not life-threatening, around 20% of cases are aggressive and are linked to poor prognoses. PSA-based screening led to death rates decreased, but overdiagnosis and consequent overtreatment has considerably increased. Hence, it is urgently necessary to develop more effective techniques that would enable reliable categorization of unfavorable intermediate-risk (uirPCa) and high-risk PCa (hrPCa), as well as to monitor quantifiable residual disease after therapy.

Early PCa events involving altered DNA methylation are easily detected in liquid biopsies and are useful for reliable diagnostic, prognostic, and response prediction tools. Herein, we aim to explore minimally invasive DNA methylation-based biomarkers suited for stratification of uirPCa and hrPCa as well as residual disease surveillance, unveiling a potential improvement in the PSA-based screening.

Publications

Sequeira JP, Salta S, Freitas R, López-López R, Díaz-Lagares Á, Henrique R, Jerónimo C. Biomarkers for Pre-Treatment Risk Stratification of Prostate Cancer Patients: A Systematic Review. Cancers (Basel). 16(7):1363, 2024. doi: 10.3390/cancers16071363.

miREpiTestis – “Unveiling miR-371-373 cluster epigenetic reprogramming and downstream targets in testicular germ cell tumors” (PI190-CI-IPOP-23-2023), Budget: 25K€ (2023-2024) (PI: Prof. Carmen Jerónimo; Co-PI Dr. João Lobo)

To date, miR-371a-3p is the most promising tumor marker of testicular germ cell tumors (TGCTs) and is expected to enter the clinic soon due to its high sensitivity and specificity. Despite undoubtful clinical utility, little is known about miR-371a-3p biology, secretion and regulatory networks. Hence, the miREpiTestis project aims to 1) uncover miR-371-373 (upstream) epigenetic regulatory mechanisms, 2) determine miR-371a-3p stemness-related (downstream) target genes, and 3) ascertain its secretion in TGCT-derived extracellular vesicles.

Publications

Lobo J, Tavares NT, Jerónimo C, Henrique R, Dvindenko E, Cornejo KM, Berney DM, Ulbright TM, Gupta S, Acosta AM. Analysis of MicroRNA-371-373 supports that a subset of spermatocytic tumors demonstrates biologic features similar to those of GCNIS-derived germ cell tumors. Hum Pathol, 48:66-71, 2024. doi: 10.1016/j.humpath.2024.05.005

Estevão-Pereira H, Guimarães-Teixeira C, Flores BT, Moreira-Silva F, Tavares NT, Guimarães R, Braga I, Maurício J, Henrique R, Jerónimo C, Lobo J. EHMT2/G9a and EZH2: Epimarkers in Testicular Germ Cell Tumors. Andrology. 2024. doi: 10.1111/andr.13604. Online ahead of print

Tavares NT*, Lobo J*, Bagrodia A. MicroRNAs for detecting occult genitourinary cancer. Curr Opin Urol, 34(1):20-26, 2024. doi: 10.1097/MOU.0000000000001137

SuHRBlac – “Surveillance of high-risk non-muscle invasive bladder cancer: validation of an epigenetics-based test in a real-world scenario” (PI191-CI-IPOP-24-2023), Budget: 9K€ (2023-2024) (PI: Prof. Carmen Jerónimo; Prof. Rui Henrique)

Even after treatment of primary tumours, bladder cancer (BC) has a high recurrence rate, which requires frequent monitoring of these patients. The SuHRBlaC project aims to evaluate the performance of a non-invasive detection test using urine as a source of DNA methylation biomarkers to detect relapsed BC. Currently, no molecular biomarker is widely used in this scenario and its implementation could help to reduce the burden of care imposed on the Health Care System.

Selected publications

• Macedo-Silva C, Miranda-Gonçalves V, Tavares NT, Barros-Silva D, Lencart J, Lobo J, Oliveira Â, Correia MP, Altucci L, Jerónimo C. Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling. Signal Transduct. Target. Ther. 8(1): 395, 2023. doi: 10.1038/s41392-023-01639-6.
• Monteiro-Reis S, Miranda-Gonçalves V, Guimarães-Teixeira C, Martins-Lima C, Lobo J, Montezuma D, Dias PC, Neyret-Kahn H, Bernard-Pierrot I, Henrique R, Jerónimo C. Vimentin epigenetic deregulation in Bladder Cancer associates with acquisition of invasive and metastatic phenotype through epithelial-to-mesenchymal transition. Int J Biol Sci. 19(1):1-12, 2023. doi: 10.7150/ijbs.77181.
• Guimarães-Teixeira C, Lobo J, Miranda-Gonçalves V, Barros-Silva D, Martins-Lima C, Monteiro-Reis S, Sequeira JP, Carneiro I, Correia MP, Henrique R, Jerónimo C. Downregulation of m6 A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness. Mol Oncol. 16(9):1841-1856, 2022. doi: 10.1002/1878-0261.13181.
• Miranda-Gonçalves V, Lobo J, Guimarães-Teixeira C, Barros-Silva D, Guimarães R, Cantante M, Braga I, Maurício J, Oing C, Honecker F, Nettersheim D, Looijenga LHJ, Henrique R, Jerónimo C. The component of the m6A writer complex VIRMA is implicated in aggressive tumor phenotype, DNA damage response and cisplatin resistance in germ cell tumors. J Exp Clin Cancer Res. 40(1):268, 2021. doi: 10.1186/s13046-021-02072-9.
• Lobo J, Constâncio V, Guimarães-Teixeira C, Leite-Silva P, Miranda-Gonçalves V, Sequeira JP, Pistoni L, Guimarães R, Cantante M, Braga I, Maurício J, Looijenga LHJ, Henrique R, Jerónimo C. Promoter methylation of DNA homologous recombination genes is predictive of the responsiveness to PARP inhibitor treatment in testicular germ cell tumors. Mol Oncol. 15(4):846-865, 2021. doi: 10.1002/1878-0261.12909.

PATENTS

(2012) Methods and biomarkers for detection of bladder cancer; US 20130210011/ EP 2630261 A1/ WO 2012052844 A1 (in collaboration Oslo University Hospital)

(2023) Prostate cancer recurrence risk calculator; Provisional Patent PT 20242005764083

NATIONAL COLLABORATIONS

Celso Reis | IPATIMUP, i3S
Fátima Baltazar & Bruno Costa | ICVS/3Bs, U. Minho
Goreti Sales | U. Coimbra
Joana Paredes | IPATIMUP, i3S
João F Mano | CICECO – U. Aveiro
João P Ferreira | FEUP
Luisa Helguero | IBiMED, U. Aveiro
Margarida Fardilha | IBiMED, U. Aveiro
Maria José Oliveira | INEB, i3S
Meriem Lamghari | INEB, i3S
Paula Guedes | REQUIMTE-FF, U. Porto
Raquel Almeida | IPATIMUP, i3S
Renato Natal Jorge | INEGI, FEUP
Sara Ricardo | 1H-TOXRUN, IUCS

INTERNATIONAL COLLABORATIONS

Aditya Bagrodia | University of California San Diego, USA
Ángel Díaz-Lagares | Epigenomics Unit, Health Research Institute of Santiago de Compostela-IDIS, Spain
Elena Martens-Uzunova | Erasmus Medical Center, Rotterdam, The Netherlands
Florence Le Calvez-Kelm | IARC, Lyon, France
Gabri van der Pluijm | Leiden University Medical Center, The Netherlands
Giuseppina Carbone | Institute of Oncology Research (IOR), Belinzona, Switzerland
Guro Lind | Radium Hospital, Oslo, Norway
Hector Peinado | CNIO, Madrid, Spain
Hing Leung | CRUK-Glasgow, UK
Isabelle Bernard-Pierrot | Institut Curie, Paris, France
Jesús M. Paramio & Marta Dueñas | Biomedical Research Institute I+12, University Hospital “12 de Octubre”, Madrid, Spain
Lucia Altucci | Università degli studi della Campania “Luigi Vanvitelli”, Naples, Italy
Marianne G. Rots | University of Groningen, The Netherlands
Marianna Kruithof-de Julio | Bern Univ Hospital, Switzerland
Mónica Martínez-Fernández | CIMUS, University of Santiago de Compostela, Spain
Paola Arimondo | Institute Pasteur, Paris, France
Sandra Blanco | Centro de Investigación del Cáncer, Salamanca, Spain
Wilbert Zwart | NKI, Amsterdam, The Netherlands
Valérie Taly | Université Paris Descartes, Paris, France

 

*The information described in the group is the sole responsibility of the respective coordinator.