Main Interests:
We are mainly interested in elucidating drug resistance mechanisms in cancer by large scale biological experiments using model systems followed by biomarker validation in clinical samples.
Research Areas:
The computational molecular medicine group (CMM) aims at being forefront in clinical proteogenomics research. We have established experimental and computational quantitative technologies for MS-based profiling useful for clinical proteomics (e.g. label free quantitation, triple dimethyl labeling and SILAC). More specifically we have more than 10 years’ experience in global MS-based drug profiling used in combination with genomics technologies such as next/third generation sequencing methodologies (Proteogenomics). We have experience in using proteogenomics in clinical samples, human cell lines and in multi-drug resistance bacteria. Our main interest is to apply our technologies on chronic diseases to contribute to precision medicine approaches. We currently have three biomarker projects funded on immune profiling in lung cancer and diffuse large B cell lymphoma. These projects will be running from 2018-2022. Although the main focus is on chronic diseases, pathogens are also questioned to address the role of host-pathogen interactions in chronic diseases. In other words, we work in the interface between clinicians, biomedical and biochemistry researchers.
Projects
Current:
2019-2025 CEEC position (FCT), CEECIND/03906/2017, investigator position.
2018-2021: Portugal 2020, 02/SAICT/2017, 30088, Immune- and microenvironment- proteogenomics profiling for classifying lung cancer patients, budget 239769,36 Euro (Principal Investigator)
2018-2021: Portugal 2020, 02/SAICT/2017, 30087, Impact of B-cell deregulated pathways on tumor immune evasion - relevance for Diffuse Large B-Cell Lymphoma therapy response-LED, budget 239769,36 Euro (Co-Principal Investigator)
2018-2020 Diffuse Large B-cell lymphoma blood based proteome signatures, iNOVA4Health, 48,125 Euro, Principal Investigator
2017-2021: MEDIRAD: Implications of Medical Low Dose Radiation Exposure (HORIZON2020 NGRP-2016-2017-1) (Participant)
2018-2022 ITN UBICODE, (Research member/associated partner) 3407194,- Euro (http://cordis.europa.eu/project/rcn/211533_en.html)
2018-2021: Recovering neurofunction and promoting neuroprotection in diabetic retinopathy, (research member), FCT ACC 02/SAICT/2017, 239769,36 Euro
2018-2021 Lysosome dysfunction in age-related diseases, (research member), FCT ACC 02/SAICT/2017, 250000,- Euro
2018-2021 Molecular mechanisms in melanin-containing compartments, 29765, (research member), FCT ACC 02/SAICT/2017, 239769,36 Euro
2018-2021 Remote ischemic post-conditioning in acute phase of ischemic stroke – disclosing novel circulating biomarkers and clinical trial for improving outcome, (research member), FCT ACC 02/SAICT/2017, 239769,36,- Euro
2018-2021 Targeting RAC1-signaling to enhance iodide-related cancer therapy, (research member), FCT ACC 02/SAICT/2017, 239769,36 Euro
2016-2019: PTDC/BBB-BEP/2463/2014 ProbeCOPD. Protease activity-based probes for Chronic Obstructive Pulmonary Disease diagnostics ~200,000.00 Euro.
2014-2018: Remote ischemic per-conditioning in acute stroke – clinical trial for improving outcome and disclosing novel circulating biomarkers, iNOVA for health, (Research member) - 100,000.00 Euro.
FCT investigator programme 2012 (Principal Investigator) – five year group leader salary.
2014-2019: National representative for the COST action PROTEOSTASIS, Principal Investigator
Previous:
2014-2015: EXPL/Current:
2019-2025 CEEC position (FCT), CEECIND/03906/2017, investigator position.
2018-2021: Portugal 2020, 02/SAICT/2017, 30088, Immune- and microenvironment- proteogenomics profiling for classifying lung cancer patients, budget 239769,36 Euro (Principal Investigator)
2018-2021: Portugal 2020, 02/SAICT/2017, 30087, Impact of B-cell deregulated pathways on tumor immune evasion - relevance for Diffuse Large B-Cell Lymphoma therapy response-LED, budget 239769,36 Euro (Co-Principal Investigator)
2018-2020 Diffuse Large B-cell lymphoma blood based proteome signatures, iNOVA4Health, 48,125 Euro, Principal Investigator
2017-2021: MEDIRAD: Implications of Medical Low Dose Radiation Exposure (HORIZON2020 NGRP-2016-2017-1) (Participant)
2018-2022 ITN UBICODE, (Research member/associated partner) 3407194,- Euro (http://cordis.europa.eu/project/rcn/211533_en.html)
2018-2021: Recovering neurofunction and promoting neuroprotection in diabetic retinopathy, (research member), FCT ACC 02/SAICT/2017, 239769,36 Euro
2018-2021 Lysosome dysfunction in age-related diseases, (research member), FCT ACC 02/SAICT/2017, 250000,- Euro
2018-2021 Molecular mechanisms in melanin-containing compartments, 29765, (research member), FCT ACC 02/SAICT/2017, 239769,36 Euro
2018-2021 Remote ischemic post-conditioning in acute phase of ischemic stroke – disclosing novel circulating biomarkers and clinical trial for improving outcome, (research member), FCT ACC 02/SAICT/2017, 239769,36,- Euro
2018-2021 Targeting RAC1-signaling to enhance iodide-related cancer therapy, (research member), FCT ACC 02/SAICT/2017, 239769,36 Euro
2016-2019: PTDC/BBB-BEP/2463/2014 ProbeCOPD. Protease activity-based probes for Chronic Obstructive Pulmonary Disease diagnostics ~200,000.00 Euro.
2014-2018: Remote ischemic per-conditioning in acute stroke – clinical trial for improving outcome and disclosing novel circulating biomarkers, iNOVA for health, (Research member) - 100,000.00 Euro.
FCT investigator programme 2012 (Principal Investigator) – five year group leader salary.
2014-2019: National representative for the COST action PROTEOSTASIS, Principal Investigator
Previous:
2014-2015: EXPL/DTP-PIC/0616/2013 “Global MS-based profiling of bronchial aspirate: targeting lung cancer specific modifications” (Principal Investigator) - 49,800.00 Euro.
2013-2015: PTDC-BEX-GMG-0242-2012 “Evaluating the role of proteolysis in the male reproductive system through the study of KLK (19q13.4) and WFDC (20q13) gene clusters.” (Research member)- ~200,000.00 Euro.
2010-2013: PTDC/QUI-BIQ/099457/2008 “Dissection of the molecular role of O-GlcNAc in the multinucleation phenotype of the neoplasic cells in Hodgkin´s lymphoma.” (Principal Investigator) ~200,000.00 Euro.
2010-2013: PTDC/EIA-EIA/099458/2008 “Computational disease prediction system based on molecular markers” (Principal Investigator) ~50,000.00 Euro.
2010-2013: PTDC/SAU-FCF/100930/2008 “Molecular and nanotechnology-based approaches to improve the antitumor activity of small molecules” (Research member) ~200,000.00 Euro.
2010-2013: PTDC/SAU-GMG/101229/2008 “Search for genomic structural variants in azoospermia: a study in Portuguese population ”
Contract with Novo Nordisk (2010) - 10,000.00 Euro.
Ramon Cajal (Principal Investigator) – five year group leader salary.
Carlsberg foundation (Principal Investigator) – two year post doc salary.
2014-2019: COST action Proteostasis. We have so far been selected for two post doctoral exchange grants (Principal Investigator).
Etortek Research Programs 2005 / 2006 (CIC bioGUNE) (Principal Investigator).
Profit (Gaiker), (research member).
La Caixa (research member).
EU Temblor (research member).
DTP-PIC/0616/2013 “Global MS-based profiling of bronchial aspirate: targeting lung cancer specific modifications” (Principal Investigator) - 49,800.00 Euro.
2013-2015: PTDC-BEX-GMG-0242-2012 “Evaluating the role of proteolysis in the male reproductive system through the study of KLK (19q13.4) and WFDC (20q13) gene clusters.” (Research member)- ~200,000.00 Euro.
2010-2013: PTDC/QUI-BIQ/099457/2008 “Dissection of the molecular role of O-GlcNAc in the multinucleation phenotype of the neoplasic cells in Hodgkin´s lymphoma.” (Principal Investigator) ~200,000.00 Euro.
2010-2013: PTDC/EIA-EIA/099458/2008 “Computational disease prediction system based on molecular markers” (Principal Investigator) ~50,000.00 Euro.
2010-2013: PTDC/SAU-FCF/100930/2008 “Molecular and nanotechnology-based approaches to improve the antitumor activity of small molecules” (Research member) ~200,000.00 Euro.
2010-2013: PTDC/SAU-GMG/101229/2008 “Search for genomic structural variants in azoospermia: a study in Portuguese population ”
Contract with Novo Nordisk (2010) - 10,000.00 Euro.
Ramon Cajal (Principal Investigator) – five year group leader salary.
Carlsberg foundation (Principal Investigator) – two year post doc salary.
2014-2019: COST action Proteostasis. We have so far been selected for two post doctoral exchange grants (Principal Investigator).
Etortek Research Programs 2005 / 2006 (CIC bioGUNE) (Principal Investigator).
Profit (Gaiker), (research member).
La Caixa (research member).
EU Temblor (research member).
Publications
- Carvalho AS, Baeta H, Silva BC, Moraes MCS, Bodo C, Beck HC, Rodriguez MS, Saraswat M, Pandey A, Matthiesen R. Extra-cellular vesicles carry proteome of cancer hallmarks. Front Biosci (Landmark Ed). 2020 Jan 1;25:398-436.
- Matthiesen R., MS-Based Biomarker Discovery in Bronchoalveolar Lavage Fluid for Lung Cancer. Proteomics Clin Appl. 2019
- Gomes S, Cavadas B, Ferreira JC, Marques PI, Monteiro C, Sucena M, Sousa C, Vaz Rodrigues L, Teixeira G, Pinto P, Tavares de Abreu T, Bárbara C, Semedo J, Mota L, Carvalho AS, Matthiesen R, Pereira L, Seixas S. Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma. Sci Rep. 2019 Sep 6;9(1):12838. doi: 10.1038/s41598-019-49195-w
- Santos JD, Canato S, Carvalho AS, Botelho HM, Aloria K, Amaral MD, Matthiesen R, Falcao AO, Farinha CM. Folding Status Is Determinant over Traffic-Competence in Defining CFTR Interactors in the Endoplasmic Reticulum. Cells. 2019 Apr 14;8(4). pii: E353. doi: 10.3390/cells8040353.
- Lima RT, Sousa D, Gomes AS, Mendes N, Matthiesen R, Pedro M, Marques F, Pinto MM, Sousa E, Vasconcelos MH, The Antitumor Activity of a Lead Thioxanthone is Associated with Alterations in Cholesterol Localization.,Molecules. 2018 Dec 12;23(12)
- Canato S, Santos JD, Carvalho AS, Aloria K, Amaral MD, Matthiesen R, Falcao AO, Farinha CM. Proteomic interaction profiling reveals KIFC1 as a factor involved in early targeting of F508del-CFTR to degradation. Cell Mol Life Sci. 2018 (Q1)
- El Motiam A, Vidal S, de la Cruz-Herrera CF, Da Silva-Álvarez S, Baz-Martínez M, Seoane R, Vidal A, Rodríguez MS, Xirodimas DP, Carvalho AS, Beck HC, Matthiesen R, Collado M, Rivas C. Interplay between SUMOylation and NEDDylation regulates RPL11 localization and function. FASEB J., 2018 Jul, 30024791 (Q1)
- Carvalho AS, Cuco CM, Lavareda C, Miguel F, Ventura M, Almeida S, Pinto P, de Abreu TT, Rodrigues LV, Seixas S, Bárbara C, Azkargorta M, Elortza F, Semedo J, Field JK, Mota L, Matthiesen R. (2017) Bronchoalveolar Lavage Proteomics in Patients with Suspected Lung Cancer. Sci Rep. 2017 Feb 7;7:42190. doi: 10.1038/srep42190.
- Carvalho AS, Molina H, Matthiesen R, New insights into functional regulation in MS-based drug profiling, Scientific Reports from Nature Publishing Group, 2016, 6, 18826.
- Lydia Mata-Cantero, Mikel Azkargorta, Fabienne Aillet, Wendy Xolalpa, Maria, J. LaFuente1, Felix Elortza, Ana Sofia Carvalho, J. Julio Martin-Plaza, Rune Matthiesen (shared corresponds)*, Manuel S. Rodriguez*, New insights into host-parasite TUBEs interactome dynamics in P. falciparum and infected red blood cells. Journal of Proteomics, 2016, S1874-3919(16)30059-8.
- Ana Sofia Carvalho, Deborah Penque and Rune Matthiesen, Bottom up proteomics data analysis strategies to explore protein modifications and genomic variants, Proteomics, 2015, 15, 1789-92.
- Ana S. Carvalho, Helena Ribeiro, Paula Voabil, Deborah Penque, Ole N. Jensen, Henrik Molina & Rune Matthiesen, Global MS- and transcriptomics array drug profiling provides novel insight into glucosamine-induced ER stress, Molecular and Cellular Proteomics, 2014, 13, 3294-307
- Elisa Da Silva-Ferrada, Fernando Lopitz-Otsoa, Valérie Lang, Manuel S. Rodriguez, Rune Matthiesen, Strategies to identify recognition signals and targets of SUMOylation, Biochemistry Research International, 2012, 2012:875148
Collaborations
1. Miguel Seabra, CEDOC: Lysosome dysfunction in age-related diseases
2. Paula Macedo, CEDOC: Exosomes in diabetes
3. Duarte Barral, CEDOC
4. Sandra Tenreiro, CEDOC: Recovering neurofunction and promoting neuroprotection in diabetic retinopathy
5. Dr. Wenjie Sun, Tulane University School of Public Health and Tropical Medicine, New Orleans, US,
Lung inflammasome and lung cancer biomarkers.
6. Mission Therapeutics – 1) Chemical probes for cancer therapies and diagnostics and 2) MS-based
global drug profiling for novel cancer drugs.
7. Dr. Manuel S. Rodriguez, France –A) Role of protein ubiquitylation in Mantle Cell Lymphoma
resistance to Bortezomib (120 LC-MS runs), B) New insights into host-parasite ubiquitin proteome
dynamics in P. falciparum infected red blood cells using TUBEs-MS approach (160 LC-MS runs) and C)
Next generation Ubiquitin and SUMO traps.
8. Professor David C Lyden and Ayuko Hoshino, Weill Cornell Medical College; Bruno Costa-Silva,
Champalimaud, Lisbon; Henrik Molina, Rockefeller University – Exosome biomarkers.
9. Dr. Carmen Rivas, Spain - PI3K signalling in cancer
10. Professor Helena Viera and Prof. Miguel Viana-Baptista, director of Hospital São Francisco Xavier.
Clinical trial for improving outcome and disclosing novel circulating biomarkers.
11. Professor Margarida D. Amaral, EMBO chair and Dr. Carlos Farinha. Dissecting the endoplasmic
reticulum quality control - differential protein interactions as new therapeutic targets in Cystic Fibrosis.
12. Dr. Susana Seixas, researcher, IPATIMUP, Porto, Portugal and Felix Elortza LC-MS runs of infertile
patients and controls (Proteogenomics).
13. Dr. Sílvia Gomes, NGS sequencing of bronchoaviolar lavage microbiome.
14. Dr. Paulo Matos, Targeting Rac1-signaling to enhance iodide-related therapy in breast cancer.
15. Dr. Susana Lucas, COPD biomarkers
16. MD Amélia Feliciano, kerman Aloria - OSA biomarkers
Two Post-Doctoral positions are available for three years at Rune Matthiesen Lab.
Motivated students are encouraged to apply. Interested candidates, please send your CV, a letter explaining your interests and the name/contact information for 1-3 references to rune.matthiesen(at)nms.unl.pt.