Where Ideas Grow

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.

The research focus of the ICG group: Glycans at the interface of Immunology and Cancer. Upper right figure illustrates mucosal T cells expressing a glycan (green) and the T Cell Receptor (red). Bottom right figure represents an aberrantly expressed glycan (red) in cancer cells.

Team

Selected Publications

Alves I., Santos-Pereira B., Dalebout H., Santos S., Vicente M.M., Campar A., Thepaut M., Fieschi F., Strahl S., Boyaval F., Vizcaíno R., Silva R., Holst-Bernal S., Vasconcelos C., Santos L., Wuhrer M., Marinho A., Heijs B., Pinho S.S.,
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

Ongoing Projects

Protein Mannosylation as a Diagnostic and Prognostic Biomarker of Lupus Nephritis: An Unusual Glycan Neoepitope in Systemic Lupus Erythematosus
Reference: Premio Pfizer/SCML 2021 Investigac?o Clinica
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Sociedade Ciências Médicas de Lisboa
From 01-DEC-21 to 31-DEC-25
Glycans as the crosstalk between gut microbiome and immune response: mechanisms and potential therapeutic applications in Inflammatory Bowel Disease
Reference: ECCO Pioneer Award 2021 - GLYCANTALK
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: European Crohn's and Colitis Organization (ECCO)
From 01-JAN-22 to 31-DEC-24
Glycans as the missing link to repair intestinal dysbiosis in Inflammatory Bowel Disease
Reference: ESCMID - Research grants 2022 - GlycoBiome
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Eur.Soc.Clinical Microb. Infect. Diseases (ESCMID)
From 01-APR-22 to 01-APR-24
Prémio SPMI - Investigação NEDAI 2022
Reference: Premio SPMI- NEDAI 2022 - S.Pinho
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Sociedade Portuguesa de Medicina Interna (SPMI)
From 01-MAY-22 to 31-DEC-24
Glycans as Master Triggers of Health to Intestinal Inflammation Transition
Reference: HORIZON-HLTH-2022-STAYHLTH-02-01-RIA- GA 101093997
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: CE - Comissão Europeia
From 01-JAN-23 to 31-DEC-28
Glycans as Master Switches of B Cell Activity in Autoimmunity
Reference: HORIZON ERC Synergy Grants - GA 101071386
Proponent: Leiden University Medical Center
Sponsor: CE - Comissão Europeia
From 01-JAN-23 to 31-DEC-28
Feeding immunity: development of a novel glycan-based dietary strategy for IBD prevention
Reference: ECCO Grants 2022 - ID 47449
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: European Crohn's and Colitis Organization (ECCO)
From 01-MAR-23 to 31-DEC-24
Unravelling the (T)Regulatory power of Glycans in Autoimmunity: mechanism and potential clinical applications
Reference: 2022.01422.PTDC
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-23 to 30-JUN-24
Turning sweet on autoimmunity: Impact of glycans in Systemic Lupus Erythematosus pathogenesis and treatment
Reference: Lupus Innovation Award 2022 -Application ID 971446
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Lupus Research Alliance
From 01-MAR-23 to 28-FEB-25
Glycans in colitis-associated colorectal cancer
Reference: DII4
Proponent: Ipatimup
Sponsor: GEDII
From 01-APR-19 to 01-MAR-24
Glycome as a predictor of IBD development
Proponent: Ipatimup
Sponsor: Departamento de Defesa Americano
From 30-SEP-19 to 30-JUN-24
A glicosilação de linfócitos T na mucosa: um novo biomarcador para melhorar o rastreio endoscópico para prevenção de Cancro Colorretal
Reference: Bolsa SPED 2023 Projetos Investigac?o
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: SPED-Sociedade Portuguesa de Endoscopia Digestiva
From 01-NOV-23 to 30-NOV-26
Host-derived mannose glycans trigger a pathogenic ?d T cell/IL-17a axis in autoimmunity
Reference: Premio SPMI- NEDAI 2023 - S.Pinho
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Sociedade Portuguesa de Medicina Interna (SPMI)
From 01-NOV-23 to 31-DEC-25
GlycanB - Decoding novel anti-glycan autoantibodies in autoimmunity
Reference: Premio SPMI- NEDAI 2023 - I.Alves
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Sociedade Portuguesa de Medicina Interna (SPMI)
From 01-JAN-24 to 31-DEC-25
Unravelling the (T)Regulatory power of Glycans in Myasthenia Gravis: mechanism and potential clinical applications
Reference: Bolsa Pereira Monteiro SPN 2023 - MGlycAn-Therapy
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: Sociedade Portuguesa de Neurologia
From 01-JAN-24 to 30-JUN-25