Immunology, Cancer & GlycoMedicine
ABOUT
Glycans (carbohydrates or sugar chains) cover the surfaces of all mammalian cells through a process called glycosylation. The diversity of glycans presentation on cell surface places them as ideal molecular sensors with an enormous potential for information display. The importance of glycans in the regulation of the immune system has been underappreciated for many years, and clearly the elucidation of how glycans integrate into the regulatory circuits that control the immune response will have a broad biological and clinical impact The major goal of our group is to understand how glycans mediate either immune-stimulatory or immune-inhibitory circuits with impact in inflammation, autoimmunity (including Inflammatory Bowel Disease and Systemic Lupus Erythematosus) and cancer, envisioning potential clinical applications.
RESEARCH
Our group is focused in the study of glycans as key mediators of the cellular and molecular processes relevant to immune tolerance, inflammation and cancer. Our work builds on the identification of an aberrantly expressed glycoform in cancer, the β1,6 GlcNAc branched N-glycans, catalysed by GnT-V enzyme, that was extensively characterized by us as a pro-malignant and pro-invasive structure (Pinho et al., Hum Mol Genet. 2009; Pinho et al., BBA 2013; Carvalho et al., Oncotarget 2016) being associated with poor survival rates of cancer patients (Carvalho et al., Oncogene 2016; Pinho and Reis, Nat Rev Cancer 2015). More recently, we found that Inflammatory Bowel Disease (IBD) patients exhibit a deficiency on the expression of branched complex N-glycans on intestinal T cells which negatively affected the T cell function and was associated with disease severity (Dias et al., Hum Mol Genet 2014). In summary, the research of our group is clustered in two main lines: 1) the characterization of the cellular and molecular mechanisms by which glycans contribute to amplify immune response in inflammation and autoimmunity (with a focus on IBD and SLE); 2) the understanding of how cancer-specific glycosignature regulates the immunological networks in cancer.
The group has a multidisciplinary background being composed of highly motivated biochemists, biologists, clinical investigators that in straight collaboration with centre hospitals share the common long term goal of performing translational research as well as preclinical and clinical validation of rational biomarkers and therapeutic strategies in inflammation, autoimmunity and cancer.
Team
Selected Publications
Protein Mannosylation as a Diagnostic and Prognostic Biomarker of Lupus Nephritis: An Unusual Glycan Neoepitope in Systemic Lupus Erythematosus. Arthritis and Rheumatology73(11):2069-2077, 2021. [Journal: Article] [CI: 13] [IF: 15,5]
DOI: 10.1002/art.41768 SCOPUS: 85114632866
Alves I., Vicente M.M., Gaifem J., Fernandes Â., Dias A.M., Rodrigues C.S., Oliveira J.C., Seixas N., Malheiro L., Abreu M.A., Castro R.S., Pinho S.S.,
SARS-CoV-2 Infection drives a glycan switch of peripheral T cells at diagnosis. Journal of Immunology207(6):1591-1598, 2021. [Journal: Article] [CI: 5] [IF: 5,4]
DOI: 10.4049/jimmunol.2100131 SCOPUS: 85114625464
Pereira M.S., Durães C., Catarino T.A., Costa J.L., Cleynen I., Novokmet M., Krištic J., Štambuk J., Conceição-Neto N., Machado J.C., Marcos-Pinto R., Magro F., Vermeire S., Lauc G., Lago P., Pinho S.S.,
Genetic Variants of the MGAT5 Gene Are Functionally Implicated in the Modulation of T Cells Glycosylation and Plasma IgG Glycome Composition in Ulcerative Colitis. Clinical and translational gastroenterology11(4):e00166, 2020. [Journal: Article] [CI: 17] [IF: 4,5]
DOI: 10.14309/ctg.0000000000000166 SCOPUS: 85084933256
Silva M.C., Fernandes Â., Oliveira M., Resende C., Correia A., de-Freitas-Junior J.C., Lavelle A., Andrade-Da-Costa J., Leander M., Xavier-Ferreira H., Bessa J., Pereira C., Henrique R.M., Carneiro F., Dinis-Ribeiro M., Marcos-Pinto R., Lima M., Lepenies B., Sokol H., Machado J.C., Vilanova M., Pinho S.S.,
Glycans as immune checkpoints: Removal of branched N-glycans enhances immune recognition preventing cancer progression. Cancer Immunology Research8(11):1407-1425, 2020. [Journal: Article] [CI: 29] [IF: 11,2]
DOI: 10.1158/2326-6066.CIR-20-0264 SCOPUS: 85100138005
Verhelst X., Dias A.M., Colombel J.F., Vermeire S., Van Vlierberghe H., Callewaert N., Pinho S.S.,
Protein Glycosylation as a Diagnostic and Prognostic Marker of Chronic Inflammatory Gastrointestinal and Liver Diseases. Gastroenterology158(1):95-110, 2020. [Journal: Review] [CI: 85] [IF: 22,7]
DOI: 10.1053/j.gastro.2019.08.060 SCOPUS: 85076136718
Pereira M.S., Maia L., Azevedo L.F., Campos S., Carvalho S., Dias A.M., Albergaria A., Lima J., Marcos-Pinto R., Lago P., Pinho S.S.,
A [Glyco] biomarker that predicts failure to standard therapy in ulcerative colitis patients. Journal of Crohn's and Colitis13(1):39-49, 2019. [Journal: Article] [CI: 17] [IF: 8,7]
DOI: 10.1093/ecco-jcc/jjy139 SCOPUS: 85057358772
Dias A.M., Correia A., Pereira M.S., Almeida C.R., Alves I., Pinto V., Catarino T.A., Mendes N., Leander M., Teresa Oliva-Teles M., Maia L., Delerue-Matos C., Taniguchi N., Lima M., Pedroto I., Marcos-Pinto R., Lago P., Reis C.A., Vilanova M., Pinho S.S.,
Metabolic control of T cell immune response through glycans in inflammatory bowel disease. Proceedings of the National Academy of Sciences of the United States of America115(20):E4651-E4660, 2018. [Journal: Article] [CI: 71] [IF: 9,6]
DOI: 10.1073/pnas.1720409115 SCOPUS: 85046964805
Pereira M.S., Alves I., Vicente M., Campar A., Silva M.C., Padrão N.A., Pinto V., Fernandes Å., Dias A.M., Pinho S.S.,
Glycans as key checkpoints of T cell activity and function. Frontiers in Immunology9(NOV):, 2018. [Journal: Review] [CI: 93] [IF: 4,7]
DOI: 10.3389/fimmu.2018.02754 SCOPUS: 85057432575
Dias A.M., Pereira M.S., Padrão N.A., Alves I., Marcos-Pinto R., Lago P., Pinho S.S.,
Glycans as critical regulators of gut immunity in homeostasis and disease. Cellular Immunology333:9-18, 2018. [Journal: Article] [CI: 22] [IF: 3,3]
DOI: 10.1016/j.cellimm.2018.07.007 SCOPUS: 85050201106
Dias A.M., Dourado J., Lago P., Cabral J., Marcos-Pinto R., Salgueiro P., Almeida C.R., Carvalho S., Fonseca S., Lima M., Vilanova M., Dinis-Ribeiro M., Reis C.A., Pinho S.S.,
Dysregulation of T cell receptor N-glycosylation: A molecular mechanism involved in ulcerative colitis. Human Molecular Genetics23(9):2416-2427, 2014. [Journal: Article] [CI: 49] [IF: 6,4]
DOI: 10.1093/hmg/ddt632 SCOPUS: 84897565140
Carvalho S., Catarino T.A., Dias A.M., Kato M., Almeida A., Hessling B., Figueiredo J., Gartner F., Sanches J.M., Ruppert T., Miyoshi E., Pierce M., Carneiro F., Kolarich D., Seruca R., Yamaguchi Y., Taniguchi N., Reis C.A., Pinho S.S.,
Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer. Oncogene35(13):1619-1631, 2016. [Journal: Article] [CI: 91] [IF: 7,5]
DOI: 10.1038/onc.2015.225 SCOPUS: 84937605601
Carvalho S., Reis C.A., Pinho S.S.,
Cadherins Glycans in Cancer: Sweet Players in a Bitter Process. Trends in Cancer2(9):519-531, 2016. [Journal: Review] [CI: 29]
DOI: 10.1016/j.trecan.2016.08.003 SCOPUS: 84989821862
Carvalho S., Oliveira T., Bartels M.F., Miyoshi E., Pierce M., Taniguchi N., Carneiro F., Seruca R., Reis C.A., Strahl S., Pinho S.S.,
O-mannosylation and N-glycosylation: Two coordinated mechanisms regulating the tumour suppressor functions of E-cadherin in cancer. Oncotarget7(40):65231-65246, 2016. [Journal: Article] [CI: 31] [IF: 5,2]
DOI: 10.18632/oncotarget.11245 SCOPUS: 84993660248
Pinho S.S., Reis C.A.,
Glycosylation in cancer: Mechanisms and clinical implications. Nature Reviews Cancer15(9):540-555, 2015. [Journal: Review] [CI: 1910] [IF: 34,2]
DOI: 10.1038/nrc3982 SCOPUS: 84940449986
Pinho S.S., Carvalho S., Marcos-Pinto R., Magalhães A., Oliveira C., Gu J., Dinis-Ribeiro M., Carneiro F., Seruca R., Reis C.A.,
Gastric cancer: Adding glycosylation to the equation. Trends in Molecular Medicine19(11):664-676, 2013. [Journal: Review] [CI: 94] [IF: 10,1]
DOI: 10.1016/j.molmed.2013.07.003 SCOPUS: 84886951831
Pinho S.S., Figueiredo J., Cabral J., Carvalho S., Dourado J., Magalhães A., Gärtner F., Mendonça A.M., Isaji T., Gu J., Carneiro F., Seruca R., Taniguchi N., Reis C.A.,
E-cadherin and adherens-junctions stability in gastric carcinoma: Functional implications of glycosyltransferases involving N-glycan branching biosynthesis, N-acetylglucosaminyltransferases III and v. Biochimica et Biophysica Acta - General Subjects1830(3):2690-2700, 2013. [Journal: Article] [CI: 98] [IF: 3,8]
DOI: 10.1016/j.bbagen.2012.10.021 SCOPUS: 84873589547
Paredes J., Figueiredo J., Albergaria A., Oliveira P., Carvalho J., Ribeiro A.S., Caldeira J., Costa A.M., Simões-Correia J., Oliveira M.J., Pinheiro H., Pinho S.S., Mateus R., Reis C.A., Leite M., Fernandes M.S., Schmitt F., Carneiro F., Figueiredo C., Oliveira C., Seruca R.,
Epithelial E- and P-cadherins: Role and clinical significance in cancer. Biochimica et Biophysica Acta - Reviews on Cancer1826(2):297-311, 2012. [Journal: Review] [CI: 175] [IF: 9]
DOI: 10.1016/j.bbcan.2012.05.002 SCOPUS: 84861800037
Pinho S.S., Oliveira P., Cabral J., Carvalho S., Huntsman D., Gärtner F., Seruca R., Reis C.A., Oliveira C.,
Loss and recovery of Mgat3 and GnT-III mediated E-cadherin N-glycosylation is a mechanism involved in epithelial-Mesenchymal-Epithelial transitions. PLoS ONE7(3):, 2012. [Journal: Article] [CI: 90] [IF: 3,7]
DOI: 10.1371/journal.pone.0033191 SCOPUS: 84858138360
Pinho S.S., Seruca R., Gärtner F., Yamaguchi Y., Gu J., Taniguchi N., Reis C.A.,
Modulation of E-cadherin function and dysfunction by N-glycosylation. Cellular and Molecular Life Sciences68(6):1011-1020, 2011. [Journal: Review] [CI: 127] [IF: 6,6]
DOI: 10.1007/s00018-010-0595-0 SCOPUS: 79953721653
De-Freitas-Junior J.C.M., Carvalho S., Dias A.M., Oliveira P., Cabral J., Seruca R., Oliveira C., Morgado-Díaz J.A., Reis C.A., Pinho S.S.,
Insulin/IGF-I signaling pathways enhances tumor cell invasion through bisecting GlcNAc N-glycans modulation. An interplay with E-cadherin. PLoS ONE8(11):, 2013. [Journal: Article] [CI: 26] [IF: 3,5]
DOI: 10.1371/journal.pone.0081579 SCOPUS: 84896731020