It is well recognized that the clinical response of immunotherapies depends on the ability of T-cells to mount an effective effector response, persist in treated patients and avoid exhaustion and toxicities. Several approaches to immunotherapy have shown promise in clinical trials, especially the use of immune checkpoint inhibitors and, more recently, autologous adoptive T-cell therapies. However, current state-of-the-art immunotherapies are only effective in a small fraction of patients, offering a medical need to be addressed in several cancer types.
Importantly, the tumor microenvironment has specific features that impact the immune response, including decreased oxygenation, aberrant vascularization and altered nutrient availability, all these influences the success of immunotherapies.
Our research is focused on elucidating the role of the oxygen sensing machinery in T cell function, and the link of hypoxia-driven metabolism and epigenetic modifications with T cell differentiation into effector and memory T cells within the context of cancer immunotherapy. Our current aims are to exploit these findings with a multi-disciplinary strategy, to deliver several early-stage drug discovery outputs. Our main objectives are:
1. Development of novel small molecule inhibitors to modulate the hypoxic response in T cells.
2. Therapeutic target discovery in T cells, focused on hypoxia-driven epigenetic modifications.
3. Development of hypoxia-responsive approaches for adoptive T cell therapy.
Successful completion of these aims will allow us to further innovate, harness this pathway for therapeutic potential and explore potential combinatorial approaches.
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Group Leader
June Ereño Orbea
Ikerbasque Research Associate POSTDOCTORAL RESEARCHER -
Amaia Mentxaka Obieta
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Lorena Pérez Gutiérrez
AECC Talent Fellow -
María Elena Laugieri
Juan de la Cierva Fellow TECHNICIANS / DOCTORAL CANDIDATES -
So Young Lee
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Iker Oyenarte
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Eunate Valdaliso Díez
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Jone Etxaniz Díaz de Durana
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Ander de Blas Martín
AECC Predoctoral Felow
Members
Latest Publications
Decoding the Molecular Basis of the Specificity of an Anti-sTn Antibody
Soares, CO; Laugieri, ME; Grosso, AS; Natale, M; Coelho, H; Behren, S; Yu, J; Cai, H; Franconetti, A; Oyenarte, I; Magnasco, M; Gimeno, A; Ramos, N; Chai, WA; Corzana, F; Westerlind, U; Jiménez-Barbero, ...
JACS AU
2024-12-16
Exploring Glycan-Lectin Interactions in Natural-Like Environments: A View Using NMR Experiments Inside Cell and on Cell Surface
Bertuzzi, S; Lete, MG; Franconetti, A; Diercks, T; Delgado, S; Oyenarte, I; Moure, MJ; Nuñez-Franco, R; Valverde, P; Lenza, MP; Sobczak, K; Jiménez-Osés, G; Paulson, JC; Ardá, A; Ereño-Orbea, ...
CHEMISTRY-A EUROPEAN JOURNAL
2024-12-11
NMR investigations of glycan conformation, dynamics, and interactions
Angulo, J; Ardá, A; Bertuzzi, S; Canales, A; Ereño-Orbea, J; Gimeno, A; Gomez-Redondo, M; Muñoz-García, JC; Oquist, P; Monaco, S; Poveda, A; Unione, L; Jiménez-Barbero, J;
PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
2024-10-18
Insights into the recognition of hypermucoviscous Klebsiella pneumoniae clinical isolates by innate immune lectins of the Siglec and galectin families
Campanero-Rhodes, MA; Martí, S; Hernández-Ortiz, N; Cubero, M; Ereño-Orbea, J; Ardá, A; Jiménez-Barbero, J; Ardanuy, C; Solís, D;
FRONTIERS IN IMMUNOLOGY
2024-08-01
Quantifying Siglec-sialylated ligand interactions: a versatile 19F-T2 CPMG filtered competitive NMR displacement assay
Atxabal, U; Fernández, A; Moure, MJ; Sobczak, K; Nycholat, C; Almeida-Marrero, V; Oyenarte, I; Paulson, JC; de la Escosura, A; Torres, T; Reichardt, NC; Jiménez-Barbero, J; Ereño-Orbea, J;
CHEMICAL SCIENCE
2024-06-07
SUMOylation controls Hu antigen R posttranscriptional activity in liver cancer
Lachiondo-Ortega, S; Rejano-Gordillo, CM; Simon, J; Lopitz-Otsoa, F; Delgado, TC; Mazan-Mamczarz, K; Goikoetxea-Usandizaga, N; Zapata-Pavas, LE; García-del Río, A; Guerra, P; Peña-Sanfélix, ...
CELL REPORTS
2024-03-26
Unraveling Molecular Recognition of Glycan Ligands by Siglec-9 via NMR Spectroscopy and Molecular Dynamics Modeling
Atxabal, U; Nycholat, C; Pröpster, JM; Fernández, A; Oyenarte, I; Lenza, MP; Franconetti, A; Soares, CO; Coelho, H; Marcelo, F; Schubert, M; Paulson, JC; Jiménez-Barbero, J; Ereño-Orbea, J;
ACS CHEMICAL BIOLOGY
2024-02-16
Targeting the Spike: Repurposing Mithramycin and Dihydroergotamine to Block SARS-CoV-2 Infection
Stagnoli, S; Macari, G; Corsi, P; Capone, B; Vidaurrazaga, A; Ereño-Orbea, J; Ardá, A; Polticelli, F; Jiménez-Barbero, J; Abrescia, NGA; Coluzza, I;
ACS OMEGA
2023-11-13
Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death
Sauve, F; Nampoothiri, S; Clarke, SA; Fernandois, D; Coêlho, CFF; Dewisme, J; Mills, EG; Ternier, G; Cotellessa, L; Iglesias-Garcia, C; Mueller-Fielitz, H; Lebouvier, T; Perbet, R; Florent, ...
EBIOMEDICINE
2023-10-01
Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b
Lenza, MP; Egia-Mendikute, L; Antoñana-Vildosola, A; Soares, CO; Coelho, H; Corzana, F; Bosch, A; Manisha, P; Quintana, JI; Oyenarte, I; Unione, L; Moure, MJ; Azkargorta, M; Atxabal, U; Sobczak, ...
NATURE COMMUNICATIONS
2023-06-13
Structures of the Inhibitory Receptor Siglec-8 in Complex with a High-Affinity Sialoside Analogue and a Therapeutic Antibody
Lenza, MP; Atxabal, U; Nycholat, C; Oyenarte, I; Franconetti, A; Quintana, JI; Delgado, S; Núñez-Franco, R; Marroquin, CTG; Coelho, H; Unione, L; Jiménez-Oses, G; Marcelo, F; Schubert, M; Paulson, ...
JACS AU
2023-01-23
The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes
Mercado-Gómez, M; Prieto-Fernández, E; Goikoetxea-Usandizaga, N; Vila-Vecilla, L; Azkargorta, M; Bravo, M; Serrano-Maciá, M; Egia-Mendikute, L; Rodríguez-Agudo, R; Lachiondo-Ortega, S; Lee, ...
COMMUNICATIONS BIOLOGY
2022-08-17
Assessing the Mobility of Severe Acute Respiratory Syndrome Coronavirus-2 Spike Protein Glycans by Structural and Computational Methods
Stagnoli, S; Peccati, F; Connell, SR; Martinez-Castillo, A; Charro, D; Millet, O; Bruzzone, C; Palazon, A; Arda, A; Jimenez-Barbero, J; Ereno-Orbea, J; Abrescia, NGA; Jimenez-Oses, G;
FRONTIERS IN MICROBIOLOGY
2022-04-15
The SARS-CoV-2 Spike Glycoprotein Directly Binds Exogeneous Sialic Acids: A NMR View
Unione, L; Moure, MJ; Lenza, MP; Oyenarte, I; Ereño-Orbea, J; Ardá, A; Jiménez-Barbero, J;
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2022-03-07
Molecular Recognition Insights of Sialic Acid Glycans by Distinct Receptors Unveiled by NMR and Molecular Modeling
Soares, CO; Grosso, AS; Ereno-Orbea, J; Coelho, H; Marcelo, F;
FRONTIERS IN MOLECULAR BIOSCIENCES
2021-11-15
Systematic Engineering of Optimized Autonomous Heavy-Chain Variable Domains
Nilvebrant, J; Ereño-Orbea, J; Gorelik, M; Julian, MC; Tessier, PM; Julien, JP; Sidhu, SS;
JOURNAL OF MOLECULAR BIOLOGY
2021-09-22
Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22
Ereño-Orbea, J; Liu, XL; Sicard, T; Kucharska, I; Li, W; Borovsky, D; Cui, H; Feng, Y; Dimitrov, DS; Julien, JP;
JOURNAL OF BIOLOGICAL CHEMISTRY
2021-08-01
Hypoxia reduces cell attachment of SARS-CoV-2 spike protein by modulating the expression of ACE2, neuropilin-1, syndecan-1 and cellular heparan sulfate
Prieto-Fernández, E; Egia-Mendikute, L; Vila-Vecilla, L; Bosch, A; Barreira-Manrique, A; Lee, SY; García-del Río, A; Antoñana-Vildosola, A; Jiménez-Lasheras, B; Moreno-Cugnon, L; Jiménez-Barbero, ...
EMERGING MICROBES & INFECTIONS
2021-01-01
Current Status on Therapeutic Molecules Targeting Siglec Receptors
Lenza, MP; Atxabal, U; Oyenarte, I; Jiménez-Barbero, J; Ereño-Orbea, J;
CELLS
2020-12-01
Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins
Lenza, MP; Oyenarte, I; Diercks, T; Quintana, JI; Gimeno, A; Coelho, H; Diniz, A; Peccati, F; Delgado, S; Bosch, A; Valle, M; Millet, O; Abrescia, NGA; Palazn, A; Marcelo, F; Jiménez-Osés, G; ...
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2020-10-22