Junior Researcher and Project Leader at i3S, where he is dissecting the role played by cancer-associated glycosylation signatures in the emergence of molecular resistance to both conventional and targeted therapies in the advanced gastric cancer setting. His work has selected for presentation in multiple international scientific meetings related to Cancer Biology, and has been awarded as both the poster and oral communication (including the Porto Cancer Meeting). He has co-authored 15 publications in internationally recognized peer-reviewed journals (including high profile publications in Trends in Cancer, Oncogene, Cancer Cell, Molecular Aspects of Medicine, FEBS Letters, Plant Biotechnology journal), and 3 book chapters edited by prestigious scientific publishers (Nova Publishers, Wiley and Elsevier).
EDUCATION
HOD has an Integrated Master in Bioengineering, with a specialization in Molecular Biotechnology (2014, FEUP/ICBAS) awarded by the University of Porto, for which he was awarded with a Merit Scholarship for Exceptional Achievement as a student of the University of Porto by the Portuguese Ministry of Education (3rd best student of the 2009-2014 class).
HOD has an interntional PhD in Molecular and Cellular Biotechnology Applied to Health Sciences (ICBAS/FFUP, University of Porto, 2020), funded by FCT and the European Association for Cancer Research (EACR). Host Institution: Glycobiology in Cancer group of the Institute for Research and Innovation in Health, University of Porto (i3S) and the Center for Proteomics and Metabolomics of the Leiden University Medical Center (CPM/LUMC), Leiden, The Netherlands.
RESEARCH, TEACHING, or OTHER INTERESTS
Biotechnology, Cancer Research, Molecular Biology, Molecular Medicine
An engineered PD1-Fc fusion produced in N. benthamiana plants efficiently blocks PD1/PDL1 interaction Shiva Izadi, Rafaela Abrantes, Simon Gumpelmair, Vinny Kunnummel, Henrique O. Duarte, et al. Plant Cell Reports, 2025 Key message Plant-made PD1–Fc fusions engineered for optimized glycosylation and Fc-receptor engagement are highly efficient in blocking PD1/PDL1 interactions and can be cost-effective alternatives to antibody-based immune checkpoint inhibitors. Abstract Immune checkpoint inhibitors (ICIs) are antibodies to receptors that have pivotal roles during T-cell activation processes. The programmed cell death 1 (PD1) can be regarded as the primary immune checkpoint and antibodies targeting PD1 or its ligand PDL1 have revolutionized immunotherapy of cancer. However, the majority of patients fail to respond, and treatment resistance as well as immune-related adverse events are commonly associated with this therapy. Alternatives to antibody-based ICIs targeting the PD1 pathway may bear the potential to overcome some of these shortcomings. Here, we have used a plant expression platform based on the tobacco relative Nicotiana benthamiana to generate immunoglobulin fusion proteins harboring the wild type or an affinity-enhanced PD1 ectodomain. We have exploited the versatility of our system to generate variants that differed regarding their glycosylation profile as well as their capability to engage Fc-receptors. Unlike its wild-type counterpart, the affinity-enhanced versions showed strongly augmented capabilities to engage PDL1 in both protein- and cell-based assays. Moreover, in contrast with clinical antibodies, their binding is not affected by the glycosylation status of PDL1. Importantly, we could demonstrate that the plant-made PD1 fusion proteins are highly efficient in blocking inhibitory PD1 signaling in a T cell reporter assay. Taken together, our study highlights the utility of our plant-based protein expression platform to generate biologics with therapeutic potential. Targeting PDL1 with plant derived affinity-enhanced PD1 immunoglobulin fusion proteins may reduce overstimulation associated with antibody-based therapies while retaining favorable features of ICIs such as long serum half-life.
Glycosylation in Cancer Henrique Oliveira Duarte, Celso Albuquerque Reis, Veronique Blanchard, Rudolf Tauber Handbook of Experimental Pharmacology, 2025
Plant-derived Durvalumab variants show efficient PD-1/PD-L1 blockade and therapeutically favourable FcR binding Shiva Izadi, Simon Gumpelmair, Pedro Coelho, Henrique O. Duarte, Joana Gomes, et al. Plant Biotechnology Journal, 2024 SummaryImmune checkpoint blocking therapy targeting the PD‐1/PD‐L1 inhibitory signalling pathway has produced encouraging results in the treatment of a variety of cancers. Durvalumab (Imfinzi®) targeting PD‐L1 is currently used for immunotherapy of several tumour malignancies. The Fc region of this IgG1 antibody has been engineered to reduce FcγR interactions with the aim of enhancing blockade of PD‐1/PD‐L1 interactions without the depletion of PD‐L1‐expressing immune cells. Here, we used Nicotiana benthamiana to produce four variants of Durvalumab (DL): wild‐type IgG1 and its ‘Fc‐effector‐silent’ variant (LALAPG) carrying further modifications to increase antibody half‐life (YTE); IgG4S228P and its variant (PVA) with Fc mutations to decrease binding to FcγRI. In addition, DL variants were produced with two distinct glycosylation profiles: afucosylated and decorated with α1,6‐core fucose. Plant‐derived DL variants were compared to the therapeutic antibody regarding their ability to (i) bind to PD‐L1, (ii) block PD‐1/PD‐L1 inhibitory signalling and (iii) engage with the neonatal Fc receptor (FcRn) and various Fcγ receptors. It was found that plant‐derived DL variants bind to recombinant PD‐L1 and to PD‐L1 expressed in gastrointestinal cancer cells and are able to effectively block its interaction with PD‐1 on T cells, thereby enhancing their activation. Furthermore, we show a positive impact of Fc amino acid mutations and core fucosylation on DL's therapeutic potential. Compared to Imfinzi®, DL‐IgG1 (LALAPG) and DL‐IgG4 (PVA)S228P show lower affinity to CD32B inhibitory receptor which can be therapeutically favourable. Importantly, DL‐IgG1 (LALAPG) also shows enhanced binding to FcRn, a key determinant of serum half‐life of IgGs.
HER2 and PD-L1 Expression in Gastric and Gastroesophageal Junction Cancer: Insights for Combinatorial Targeting Approaches Marta Baptista Freitas, Irene Gullo, Dina Leitão, Lúcia Águas, Carla Oliveira, et al. Cancers, 2024 Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.
Candida albicans chitinase 3 with potential as a vaccine antigen: production, purification, and characterisation Augusto Costa‐Barbosa, Diogo Ferreira, Maria Inês Pacheco, Margarida Casal, Henrique Oliveira Duarte, et al. Biotechnology Journal, 2024 Chitinases are widely studied enzymes that have already found widespread application. Their continued development and valorisation will be driven by the identification of new and improved variants and/or novel applications bringing benefits to industry and society. We previously identified a novel application for chitinases wherein the Candida albicans cell wall surface chitinase 3 (Cht3) was shown to have potential in vaccine applications as a subunit antigen against fungal infections. In the present study, this enzyme was investigated further, developing production and purification protocols, enriching our understanding of its properties, and advancing its application potential. Cht3 was heterologously expressed in Pichia pastoris and a 4‐step purification protocol developed and optimised: this involves activated carbon treatment, hydrophobic interaction chromatography, ammonium sulphate precipitation, and gel filtration chromatography. The recombinant enzyme was shown to be mainly O‐glycosylated and to retain the epitopes of the native protein. Functional studies showed it to be highly specific, displaying activity on chitin, chitosan, and chito‐oligosaccharides larger than chitotriose only. Furthermore, it was shown to be a stable enzyme, exhibiting activity, and stability over broad pH and temperature ranges. This study represents an important step forward in our understanding of Cht3 and contributes to its development for application.
CAR-Ts: new perspectives in cancer therapy Rafaela Abrantes, Henrique O. Duarte, Catarina Gomes, Sébastien Wälchli, Celso A. Reis FEBS Letters, 2022 Chimeric antigen receptor (CAR)‐T‐cell therapy is a promising anticancer treatment that exploits the host's immune system to fight cancer. CAR‐T cell therapy relies on immune cells being modified to express an artificial receptor targeting cancer‐specific markers, and infused into the patients where they will recognize and eliminate the tumour. Although CAR‐T cell therapy has produced encouraging outcomes in patients with haematologic malignancies, solid tumours remain challenging to treat, mainly due to the lack of cancer‐specific molecular targets and the hostile, often immunosuppressive, tumour microenvironment. CAR‐T cell therapy also depends on the quality of the injected product, which is closely connected to CAR design. Here, we explain the technology of CAR‐Ts, focusing on the composition of CARs, their application, and limitations in cancer therapy, as well as on the current strategies to overcome the challenges encountered. We also address potential future targets to overcome the flaws of CAR‐T cell technology in the treatment of cancer, emphasizing glycan antigens, the aberrant forms of which attain high tumour‐specific expression, as promising targets for CAR‐T cell therapy.
Targeting cancer cell sialylation with monosaccharide analogues modulates EGFR in colorectal cancer cells J Gotti, R do Vale, HO Duarte, AF Costa, I Andújar-Martinez, R Burock, ... Biochimica et Biophysica Acta (BBA)-General Subjects, 130955 , 2026 2026
Patient-derived organoids to study glycosylation dynamics during gastric disease L Santos-Ferreira, ÁM Martins, HO Duarte, E Moia, AF Costa, AH de Ru, ... Cell Reports 44 (11) , 2025 2025 Citations: 5
Glycosylation in Cancer CA Reis, V Blanchard, HO Duarte, CA Reis, V Blanchard, F Pfrengle Complex Carbohydrates in Health and Disease, 243 , 2025 2025
Glycosylation in Cancer HO Duarte, CA Reis, V Blanchard, R Tauber Complex Carbohydrates in Health and Disease, 243-293 , 2025 2025 Citations: 4
An engineered PD1-Fc fusion produced in N. benthamiana plants efficiently blocks PD1/PDL1 interaction S Izadi, R Abrantes, S Gumpelmair, V Kunnummel, HO Duarte, ... Plant Cell Reports 44 (4), 80 , 2025 2025 Citations: 5
Plant‐derived Durvalumab variants show efficient PD‐1/PD‐L1 blockade and therapeutically favourable FcR binding S Izadi, S Gumpelmair, P Coelho, HO Duarte, J Gomes, J Leitner, ... Plant Biotechnology Journal 22 (5), 1224-1237 , 2024 2024 Citations: 8
HER2 and PD-L1 expression in gastric and gastroesophageal junction cancer: insights for combinatorial targeting approaches MB Freitas, I Gullo, D Leitão, L Águas, C Oliveira, A Polónia, J Gomes, ... Cancers 16 (6), 1227 , 2024 2024 Citations: 9
Monensin as potential drug for treatment of SLeX-positive tumors AF Costa, E Senra, D Campos, I Faria-Ramos, L Santos-Ferreira, ... medRxiv, 2024.03. 11.24304048 , 2024 2024 Citations: 5
Candida albicans chitinase 3 with potential as a vaccine antigen: production, purification, and characterisation A Costa‐Barbosa, D Ferreira, MI Pacheco, M Casal, HO Duarte, C Gomes, ... Biotechnology Journal 19 (1), 2300219 , 2024 2024 Citations: 7
Candida albicans chitinase 3 with potential as a vaccine antigen: production, purification, and characterisation AAC Barbosa, D Ferreira, MI Pacheco, M Casal, HO Duarte, C Gomes, ... 2024
Targeting carbohydrates in cancer–analytical and biotechnological tools HO Duarte, J Gomes, CA Reis Carbohydrate‐Based Therapeutics, 161-200 , 2023 2023 Citations: 2
Glycans and Cancer A Magalhães, HO Duarte, CA Reis Academic Press , 2023 2023 Citations: 1
Insights on ErbB glycosylation–contributions to precision oncology HO Duarte, CA Reis, J Gomes Trends in Cancer 8 (6), 448-455 , 2022 2022 Citations: 16
Glycans as targets for drug delivery in cancer F Diniz, P Coelho, HO Duarte, B Sarmento, CA Reis, J Gomes Cancers 14 (4), 911 , 2022 2022 Citations: 54
CAR‐Ts: new perspectives in cancer therapy R Abrantes, HO Duarte, C Gomes, S Wälchli, CA Reis FEBS letters 596 (4), 403-416 , 2022 2022 Citations: 39
The role of O-glycosylation in human disease A Magalhães, HO Duarte, CA Reis Molecular Aspects of Medicine 79, 100964 , 2021 2021 Citations: 183
ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab HO Duarte, JG Rodrigues, C Gomes, PJ Hensbergen, ALH Ederveen, ... Oncogene 40 (21), 3719-3733 , 2021 2021 Citations: 73
Aberrant protein glycosylation in cancer: implications in targeted therapy JG Rodrigues, HO Duarte, CA Reis, J Gomes Biochemical Society Transactions 49 (2), 843-854 , 2021 2021 Citations: 29
Terminal α2, 6-sialylation of epidermal growth factor receptor modulates antibody therapy response of colorectal cancer cells JG Rodrigues, HO Duarte, C Gomes, M Balmana, AM Martins, ... Cellular Oncology 44 (4), 835 , 2021 2021 Citations: 46
Expression of Thomsen–Friedenreich Antigen in Colorectal Cancer and Association with Microsatellite Instability B Leao, X Wen, HO Duarte, I Gullo, G Goncalves, P Pontes, C Castelli, ... International Journal of Molecular Sciences 22 (3), 1340 , 2021 2021 Citations: 9
MOST CITED SCHOLAR PUBLICATIONS
The role of O-glycosylation in human disease A Magalhães, HO Duarte, CA Reis Molecular Aspects of Medicine 79, 100964 , 2021 2021 Citations: 183
Aberrant glycosylation in cancer: a novel molecular mechanism controlling metastasis A Magalhães, HO Duarte, CA Reis Cancer cell 31 (6), 733-735 , 2017 2017 Citations: 174
ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab HO Duarte, JG Rodrigues, C Gomes, PJ Hensbergen, ALH Ederveen, ... Oncogene 40 (21), 3719-3733 , 2021 2021 Citations: 73
MicroRNA-27a-5p regulation by promoter methylation and MYC signaling in prostate carcinogenesis D Barros-Silva, P Costa-Pinheiro, H Duarte, EJ Sousa, AF Evangelista, ... Cell death & disease 9 (2), 167 , 2018 2018 Citations: 72
Mucin-Type O -Glycosylation in Gastric Carcinogenesis HO Duarte, D Freitas, C Gomes, J Gomes, A Magalhaes, CA Reis Biomolecules 6 (3), 33 , 2016 2016 Citations: 59
Glycans as targets for drug delivery in cancer F Diniz, P Coelho, HO Duarte, B Sarmento, CA Reis, J Gomes Cancers 14 (4), 911 , 2022 2022 Citations: 54
Gastric cancer: basic aspects HO Duarte, J Gomes, JC Machado, CA Reis Helicobacter 23, e12523 , 2018 2018 Citations: 50
Terminal α2, 6-sialylation of epidermal growth factor receptor modulates antibody therapy response of colorectal cancer cells JG Rodrigues, HO Duarte, C Gomes, M Balmana, AM Martins, ... Cellular Oncology 44 (4), 835 , 2021 2021 Citations: 46
Gastric cancer cell glycosylation as a modulator of the ErbB2 oncogenic receptor HO Duarte, M Balmaña, S Mereiter, H Osório, J Gomes, CA Reis International journal of molecular sciences 18 (11), 2262 , 2017 2017 Citations: 46
CAR‐Ts: new perspectives in cancer therapy R Abrantes, HO Duarte, C Gomes, S Wälchli, CA Reis FEBS letters 596 (4), 403-416 , 2022 2022 Citations: 39
Aberrant protein glycosylation in cancer: implications in targeted therapy JG Rodrigues, HO Duarte, CA Reis, J Gomes Biochemical Society Transactions 49 (2), 843-854 , 2021 2021 Citations: 29
Insights on ErbB glycosylation–contributions to precision oncology HO Duarte, CA Reis, J Gomes Trends in Cancer 8 (6), 448-455 , 2022 2022 Citations: 16
HER2 and PD-L1 expression in gastric and gastroesophageal junction cancer: insights for combinatorial targeting approaches MB Freitas, I Gullo, D Leitão, L Águas, C Oliveira, A Polónia, J Gomes, ... Cancers 16 (6), 1227 , 2024 2024 Citations: 9
Expression of Thomsen–Friedenreich Antigen in Colorectal Cancer and Association with Microsatellite Instability B Leao, X Wen, HO Duarte, I Gullo, G Goncalves, P Pontes, C Castelli, ... International Journal of Molecular Sciences 22 (3), 1340 , 2021 2021 Citations: 9
Plant‐derived Durvalumab variants show efficient PD‐1/PD‐L1 blockade and therapeutically favourable FcR binding S Izadi, S Gumpelmair, P Coelho, HO Duarte, J Gomes, J Leitner, ... Plant Biotechnology Journal 22 (5), 1224-1237 , 2024 2024 Citations: 8
Candida albicans chitinase 3 with potential as a vaccine antigen: production, purification, and characterisation A Costa‐Barbosa, D Ferreira, MI Pacheco, M Casal, HO Duarte, C Gomes, ... Biotechnology Journal 19 (1), 2300219 , 2024 2024 Citations: 7
MicroRNA-27a-5p regulation by promoter methylation and MYC signaling in prostate carcinogenesis. Cell Death Dis 9: 167 D Barros-Silva, P Costa-Pinheiro, H Duarte, EJ Sousa, AF Evangelista, ... View at Publisher| View at , 2018 2018 Citations: 6
Patient-derived organoids to study glycosylation dynamics during gastric disease L Santos-Ferreira, ÁM Martins, HO Duarte, E Moia, AF Costa, AH de Ru, ... Cell Reports 44 (11) , 2025 2025 Citations: 5
An engineered PD1-Fc fusion produced in N. benthamiana plants efficiently blocks PD1/PDL1 interaction S Izadi, R Abrantes, S Gumpelmair, V Kunnummel, HO Duarte, ... Plant Cell Reports 44 (4), 80 , 2025 2025 Citations: 5
Monensin as potential drug for treatment of SLeX-positive tumors AF Costa, E Senra, D Campos, I Faria-Ramos, L Santos-Ferreira, ... medRxiv, 2024.03. 11.24304048 , 2024 2024 Citations: 5