Functional Biochemistry and Proteomics | - CCMAR -

Functional Biochemistry and Proteomics

Short Title 

The overall research strategy of FBP is driven primarily by the need to translate strong basic science into clinically relevant advances and promoting transfer of technology, based on the integration of high quality multi-disciplinary academic, researcher and clinical activity with a strong focus on translational research.




The overall research strategy of FBP is driven primarily by the need to translate strong basic science into clinically relevant advances and promoting transfer of technology. FBP strategy is based on the integration of high quality multi-disciplinary academic, researcher and clinical activity with a strong focus on translational research.

FBP research team has long expertise in the biochemical aspects of vitamin K-dependent proteins (VKD) and aparticularly unique knowledge about the biochemistry, molecular biology and biomedical aspects of a new VKD member, Gla rich protein (GRP) for which methods and assays are proprietary IP (PCT/PT2009/000046).

Our research interests include the study of GRP and otherkey genes involved in processes of ectopic calcificationand inflammation related diseases such as atherosclerosis, cancer, osteoarthritis, renal disease and diabetes. Through a combination of in vivo studies using human biological samples and in vitro and ex vivo model systems, our research aims to establish new molecular knowledge on the pathophysiology and molecular mechanisms behind the onset and development of these highly prevalentdiseases. The output obtained will most certainly contribute to the prognostic, diagnostic and clinic therapeutics for pathological calcification and inflammation related diseases.

The research activities of FBP also include the exploitation of marine resources and the discovery and validation of natural products derived from marine organisms as novel pharmaceutical, health care and personal products to address key societal challenges. Novel drug leads are tested and developed using pre-clinical assays before clinical testing and translation into medical care or as potential and innovative cosmetics.

Main areas of research

The use of established pre-clinical human cell and tissue culture models, complemented with in vivo studies using a collection of well characterized human samples, for the study ofnovel intervening molecules and molecular mechanisms involved in highly prevalent diseases

Searching for novel disease biomarkers in circulation using collected human biological samples and correlation with clinical information.

Studies on the potential of circulating extracellular vesicles as novel biomarkers and drug delivery systems, with high diagnostic andtherapeutic value for calcification and inflammatory related diseases.
The use of in vitro and ex-vivo cell human modelsas pre-clinical assays for discovery and validationof marine bioactive products as novel diseasemodifying drugs (DMDs) and unveil theirmechanism of action.

Testing bioproducts from marine resources that could become potential and innovative cosmetics.



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Coordenador Posição
Dina Simes Senior Researcher
Nome Posição
Carla Alexandra São Bento Viegas Research Assistant
Catarina Marreiros Research Technician
Dina Simes Senior Researcher
Hanaa Zbakh Research Assistant
Nuna Cláudia Peixoto de Araújo PhD Student
Ver em grelha
Retrato de Carla Alexandra São Bento Viegas
Research Assistant
Retrato de Catarina Marreiros
Research Technician
Retrato de Dina Simes
Senior Researcher
Retrato de Hanaa Zbakh
Research Assistant
Retrato de Nuna Cláudia Peixoto de Araújo
PhD Student
Antigos Membros
Other Past Members 
Sofia Cavaco
Marta Rafael
Ruben Costa
Lúcia Santos
Inês Perrolas
Sofia Santos
Inês Luis
Diego Gerini
Kevin Astorga
Todas publicações
Simes DC, Viegas CSB, Araujo NC. Vitamin K as a Powerful Micronutrient in Aging and Age-Related Diseases: Pros and Cons from Clinical Studies. 2019.
The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts. 2019. doi:10.18632/aging.102046
Viegas C, Edelweiss E, Schneider J, et al. Use of an innovative system and nanotechnology-based strategy for therapeutic applications of Gla-rich protein (GRP). Annals of Medicine. 2019;51(sup1):38 - 38. doi:10.1080/07853890.2018.1561804
Araújo N, Viegas C, Perrolas I, et al. Amentadione is a new modulating agent for osteoarthritis in an ex-vivo co-culture preclinical assay. Annals of Medicine. 2019;51(sup1):43 - 43. doi:10.1080/07853890.2018.1561895
Viegas CSB, Simes DC. A dual role for GRP in cardiovascular disease. Aging. 2019;11(5):1323 - 1324. doi:10.18632/aging.v11i510.18632/aging.101851
Viegas CSB, Simes DC. Immunity And Inflammation In Health And Disease: Inflammation And Calcification In The Vascular Tree; Insights Into Atherosclerosis. Elsevier; 2018:189 - 201. doi:10.1016/B978-0-12-805417-8.00015-9
Viegas CSB, Macedo AL, Matos AA, et al. Translational Research and Innovation in Human and Health Science: Gla-rich protein, a vitamin K-dependent protein involved in inflammation and calcification-related diseases. Annals of Medicine. 2018;50(sup1):S1 - S9. doi:10.1080/07853890.2018.1427452
Willems BA, Furmanik M, Caron MMJ, et al. Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-23353-y
Viegas CSB, Santos L, Macedo AL, et al. Chronic Kidney Disease Circulating Calciprotein Particles and Extracellular Vesicles Promote Vascular Calcification. Arteriosclerosis, Thrombosis, and Vascular Biology. 2018;38(3):575 - 587. doi:10.1161/ATVBAHA.117.310578
Silva APaula, Viegas C, Simes D, et al. GLA-RICH PROTEIN AS A NOVEL MARKER FOR CALCIFICATIONS IN DIABETIC PATIENTS WITH CKD. Nephrology Dialysis Transplantation. 2018;33(suppl_1):i493 - i493. doi:10.1093/ndt/gfy104.SP430
Viegas CSB, Costa RM, Santos L, et al. Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases. . de Frutos PGarcia, ed. PLOS ONE. 2017;12(5):e0177829.
Viegas CSB, Macedo AL, Morais R, et al. Dysregulated fetuin–mineral complexes are linked to vascular calcification in chronic kidney disease: The role of Gla-rich protein. Ultrastructural Pathology. 2017;41(1):78 - 80. doi:10.1080/01913123.2016.1269490
Morais R, Viegas CSB, Simes DC, Matos APA, Macedo AL. Application of TEM techniques for the study of vascular calcification: Monitoring extracellular vesicles and nanogold immunodetection of fetuin-A, GRP, and CD9. Ultrastructural Pathology. 2017;41(1):130 - 132. doi:10.1080/01913123.2016.1272670
Viegas C, Santos L, Macedo A, et al. CIRCULATING CALCIPROTEIN PARTICLES AND EXTRACELLULAR VESICLES AS NOVEL PLAYERS IN CHRONIC KIDNEY DISEASE VASCULAR CALCIFICATION. A ROLE FOR GLA-RICH PROTEIN. Nephrology Dialysis Transplantation. 2017;32(suppl_3):iii67 - iii68. doi:10.1093/ndt/gfx123.MO055
Viegas CSB, Simes DC. Gla-rich Protein (GRP): A New Player In The Burden Of Vascular Calcification. Journal of Cardiovascular Diseases & Diagnosis. 2016;4(4). doi:10.4172/2329-951710.4172/2329-9517.1000245
Cavaco S, Viegas CSB, Rafael MS, et al. Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis. Cell Mol Life Sci. 2016;73(5):1051-65. doi:10.1007/s00018-015-2033-9
Macedo AL, Viegas CSB, Matos APA, Simes DC. Extracellular Vesicles and Circulating Fetuin-Mineral Complexes in Vascular Calcification; Studies by EM Techniques. Microscopy and Microanalysis. 2016;22(S4):16 - 17. doi:10.1017/S1431927616000271
Viegas CSB, Simes DC. New Perspectives for the Nutritional Value of Vitamin K in Human Health. Journal of Nutritional Disorders & Therapy. 2016;6(3). doi:10.4172/2161-050910.4172/2161-0509.1000192
Richard N, Engrola S, Palma PS, Simes DC, Conceição LEC. Assessment of protein digestive capacity and metabolic utilisation during ontogeny of Senegalese sole larvae: A tracer study using in vivo produced radiolabelled polypeptide fractions. Aquaculture. 2015;441:35 - 44. doi:10.1016/j.aquaculture.2015.02.003
Viegas CSB, Rafael MS, Enriquez JL, et al. Gla-rich protein (GRP) is a new player in mineralization-competence of extracellular vesicles involved in vascular calcification. Journal of Vascular Research. 2015;52(1):1 - 88. doi:10.1159/000433498
Viegas CSB, Rafael MS, Enriquez JL, et al. Gla-rich protein acts as a calcification inhibitor in the human cardiovascular system. Arterioscler Thromb Vasc Biol. 2015;35(2):399-408. doi:10.1161/ATVBAHA.114.304823
Cavaco S, Williamson MK, Rosa J, et al. Teleost fish osteocalcin 1 and 2 share the ability to bind the calcium mineral phase. Fish Physiol Biochem. 2014;40(3):731-8. doi:10.1007/s10695-013-9880-9
Rafael MS, Cavaco S, Viegas CSB, et al. Insights into the association of Gla-rich protein and osteoarthritis, novel splice variants and γ-carboxylation status. Mol Nutr Food Res. 2014;58(8):1636-46. doi:10.1002/mnfr.201300941
Viegas CSB, Herfs M, Rafael MS, et al. Gla-rich protein is a potential new vitamin K target in cancer: evidences for a direct GRP-mineral interaction. Biomed Res Int. 2014;2014:340216. doi:10.1155/2014/340216
Viegas CSB, Simes DC, Williamson MK, et al. Sturgeon osteocalcin shares structural features with matrix Gla protein: evolutionary relationship and functional implications. J Biol Chem. 2013;288(39):27801-11. doi:10.1074/jbc.M113.450213
Oliveira DV, Silva TS, Cordeiro OD, Cavaco SI, Simes DC. Identification of proteins with potential osteogenic activity present in the water-soluble matrix proteins from Crassostrea gigas nacre using a proteomic approach. ScientificWorldJournal. 2012;2012:765909. doi:10.1100/2012/765909
Viegas CSB, Conceição N, Fazenda C, Simes DC, M. Cancela L. Expression of Gla-rich protein (GRP) in newly developed cartilage-derived cell cultures from sturgeon ( Acipenser naccarii ). Journal of Applied Ichthyology. 2010;26(2):214 - 218. doi:10.1111/jai.2010.26.issue-210.1111/j.1439-0426.2010.01408.x
Roberto VP, Cavaco S, Viegas CSB, et al. Matrix Gla protein in turbot (Scophthalmus maximus): Gene expression analysis and identification of sites of protein accumulation. Aquaculture. 2009;294(3-4):202 - 211. doi:10.1016/j.aquaculture.2009.06.020
Viegas CSB, Cavaco S, Neves PL, et al. Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications. Am J Pathol. 2009;175(6):2288-98. doi:10.2353/ajpath.2009.090474
Viegas CSB, Simes DC, Laizé V, Williamson MK, Price PA, M. Cancela L. Gla-rich protein (GRP), a new vitamin K-dependent protein identified from sturgeon cartilage and highly conserved in vertebrates. J Biol Chem. 2008;283(52):36655-64. doi:10.1074/jbc.M802761200
Rønnestad I, Gavaia P, Viegas CSB, et al. Oligopeptide transporter PepT1 in Atlantic cod (Gadus morhua L.): cloning, tissue expression and comparative aspects. J Exp Biol. 2007;210(Pt 22):3883-96. doi:10.1242/jeb.007898
Laizé V, Viegas CSB, Price PA, M. Cancela L. Identification of an osteocalcin isoform in fish with a large acidic prodomain. Journal of Biological Chemistry. 2006;281(22):15037-15043. doi:10.1074/jbc.M600373200
Simões B, Conceição N, Viegas CSB, et al. Identification of a promoter element within the zebrafish colXalpha1 gene responsive to runx2 isoforms Osf2/Cbfa1 and til-1 but not to pebp2alphaA2. Calcif Tissue Int. 2006;79(4):230-44. doi:10.1007/s00223-006-0111-6
Gavaia P, Simes DC, Ortiz-Delgado JB, et al. Osteocalcin and matrix Gla protein in zebrafish (Danio rerio) and Senegal sole (Solea senegalensis): comparative gene and protein expression during larval development through adulthood. Gene Expr Patterns. 2006;6(6):637-52. doi:10.1016/j.modgep.2005.11.010
Ortiz-Delgado JB, Simes DC, Viegas CSB, Schaff BJ, Sarasquete C, M. Cancela L. Cloning of matrix Gla protein in a marine cartilaginous fish, Prionace glauca: preferential protein accumulation in skeletal and vascular systems. Histochem Cell Biol. 2006;126(1):89-101. doi:10.1007/s00418-005-0125-6
Pinto JP, Conceição NM, Viegas CSB, et al. Identification of a New pebp2αA2 Isoform From Zebrafish runx2 Capable of Inducing Osteocalcin Gene Expression In Vitro. Journal of Bone and Mineral Research. 2005;20(8):1440 - 1453. doi:10.1359/JBMR.050318
Laizé V, Martel P, Viegas CSB, Price PA, M. Cancela L. Evolution of matrix and bone  gamma-carboxyglutamic acid proteins in vertebrates. Journal of Biological Chemistry. 2005;280(29):26659-26668. doi:10.1074/jbc.M500257200
Laizé V, Martel P, Viegas CSB, Price PA, M. Cancela L. Evolution of matrix and bone gamma-carboxyglutamic acid proteins in vertebrates. J Biol Chem. 2005;280(29):26659-68. doi:10.1074/jbc.M500257200
Ortiz-Delgado JB, Simes DC, Gavaia P, Sarasquete C, M. Cancela L. Osteocalcin and matrix GLA protein in developing teleost teeth: identification of sites of mRNA and protein accumulation at single cell resolution. Histochem Cell Biol. 2005;124(2):123-30. doi:10.1007/s00418-005-0015-y
Pinto JP, Conceição NM, Viegas CSB, et al. Identification of a new pebp2alphaA2 isoform from zebrafish runx2 capable of inducing osteocalcin gene expression in vitro. J Bone Miner Res. 2005;20(8):1440-53. doi:10.1359/JBMR.050318
Frazão C, Simes DC, Coelho R, et al. Structural evidence of a fourth Gla residue in fish osteocalcin: biological implications. Biochemistry. 2005;44(4):1234-42. doi:10.1021/bi048336z
Simes DC, Williamson MK, Schaff BJ, et al. Characterization of osteocalcin (BGP) and matrix Gla protein (MGP) fish specific antibodies: validation for immunodetection studies in lower vertebrates. Calcif Tissue Int. 2004;74(2):170-80. doi:10.1007/s00223-003-0079-4
Gavaia P, Ortiz JB, Simes DC, Sarasquete MC, M. Cancela L. SIMULTANEOUS DETECTION OF OSTEOCALCIN AND MATRIX GLA PROTEIN IN DEVELOPMENTAL STAGES OF ZEBRA FISH (DANIO RERIO). Calcified Tissue International. 2003;72:314 - 468. doi:10.1007/s00223-003-5002-5
Simes DC, Williamson MK, Ortiz-Delgado JB, Viegas CSB, Price PA, M. Cancela L. Purification of matrix Gla protein from a marine teleost fish, Argyrosomus regius: calcified cartilage and not bone as the primary site of MGP accumulation in fish. J Bone Miner Res. 2003;18(2):244-59. doi:10.1359/jbmr.2003.18.2.244
Araújo NCP, Barroca PMM, Bickley JF, et al. Structural effects on sigmatropic shifts in heteroaromatic allyl ethersElectronic supplementary information (ESI) available: selected crystal data for compound 7. See Journal of the Chemical Society, Perkin Transactions 1. 2002;(9):1213 - 1219. doi:10.1039/b102674g
Viegas CSB, Pinto JP, Conceição N, Simes DC, M. Cancela L. Cloning and characterization of the cDNA and gene encoding Xenopus laevis osteocalcin. Gene. 2002;289(1-2):97-107.
M. Cancela L, Ohresser MC, Reia JP, Viegas CSB, Williamson MK, Price PA. Matrix Gla protein in Xenopus laevis: molecular cloning, tissue distribution, and evolutionary considerations. J Bone Miner Res. 2001;16(9):1611-21. doi:10.1359/jbmr.2001.16.9.1611
Tipo de Evento 
Carla Viegas will join us on 28 th of June to talk about "Unveiling the dual role of Gla-rich protein (GRP) in the crosstalk between inflammation and calcification in pathological processes". Don't...
Qua, 28/06/2017
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Carla Alexandra São Bento Viegas, PhD, postdoctoral researcher, Functional Biochemistry and Proteomics group headed by Professor Dina Simes, PhD, Center of Marine Sciences, University of Algarve, Faro