Ikerbasque Research Associate
0000-0001-8982-1857
Ramón y Cajal (RyC) Programme - Ikerbasque Research Associate0000-0002-7172-7229June Ereño-Orbea obtained her BSc in Biochemistry and a MSc in Molecular Biology & Biomedicine from the University of Basque Country (UPV/EHU) and continued her scientific pursuits by completing her PhD in Molecular Biology and Biomedicine from the same institution.
In 2015, Dr. Ereño-Orbea joined the laboratory of Dr. Julien at SickKids Hospital (Canada). In her postdoctoral research she characterized the structure of CD22 (Siglec-2), a key inhibitory co-receptor of B cells and a significant immunotherapeutic target. This research illuminated the interactions between CD22 and sialic acid glycans and provided insights into its spatial organization within B cells. The findings contributed to advancements in antibody-based therapies, specifically CAR-T cells for B-cell lymphoma treatment. Additionally, Dr. Ereño collaborated on HIV vaccine design with The Scripps Research Institute (USA).
In 2019, Dr. Ereño-Orbea joined CIC bioGUNE and completed a successful 5-year tenure-track period as an Ikerbasque Research Fellow (2019-2023). In 2024, she got promoted to Ikerbasque Research Associate and Associated Principal Investigator to lead her independent research. Her research is focused on unraveling molecular mechanisms of antibodies and lectins, particularly exploring Siglec glycoimmune checkpoint receptors for next-generation therapies in diseases like cancer. Using integrative molecular and structural biology and biophysical techniques, she unravels the complexities of antibody-Siglec and glycan-Siglec interactions, laying the foundation for purpose-fit therapeutic molecules through protein engineering and chemical biology. Simultaneously, she delves into the generation and characterization of antibodies targeting tumor associated glycans, contributing to advancements in cancer immunotherapy.
Awards & recognitions
Ikerbasque Research Associate awarded by the Basque Foundation for Science (2024). “Consolidación Investigadora” by the Spanish Ministry of Science, Innovation and Universities (2024). R3 certificate by the Spanish Ministry of Science, Innovation and Universities (2023). BBVA Leonardo Grant for scientists and creators (2023). Ikerbasque Research Fellow awarded by the Basque Foundation for Science (2019). Juan de la Cierva Incorporación Program awarded by the Spanish Ministry of Science and Innovation (2019). Banting Postdoctoral Research Fellow from the Canadian Institutes of Health Research (CIHR) (2016). AUSE PhD Award from the Spanish Association of Synchrotron Users (2017). Restracomp Award for Postdoctoral Research from The Hospital for Sick Children, Canada (2016). Jose Tormo Prize awarded by the Spanish Society of Biochemistry and Molecular Biology (SEBBM) (2014). Predoctoral Mobility Grants awarded by the Basque Regional Government for a research stay at the University of Colorado, US (2013). Research Staff Training Predoctoral Program awarded by the Basque Regional Government (2011).
Collaborations
Collaborations are integral to her research, extending across Europe, North America, and Japan. Notable partnerships include esteemed institutions like the University Nova Lisbon (F. Marcelo, P. Videira), University of Berlin (M. Schubert), Radboud University (T. Boltje), Scripps, University of Alberta (M. Macauley), the Scripps Research Institute (J. Paulson), and Tokyo Medical and Dental University (T. Tsubata). Additionally, collaborations with Basque entities such as CIC biomaGUNE, Biofisika, Biolan, and Zelula Biopharma S.L. have enriched and expanded the impact of her investigations.
Latest Publications
2023
2022
2021
2020
2019
2018
It is well recognised 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 influence 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
Asís Palazón
Ramón y Cajal (RyC) Programme - Ikerbasque Research Associate POSTDOCTORAL RESEARCHER -
María Elena Laugieri
Juan de la Cierva Fellow -
Lorena Pérez Gutiérrez
Juan de la Cierva Fellow TECHNICIANS / DOCTORAL CANDIDATES -
Paloma Velasco Beltrán
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Jone Etxaniz Díaz de Durana
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Ander de Blas Martín
AECC Predoctoral Felow -
Klaudia Sobczak
MSCA-ITN Fellow -
Iker Oyenarte
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Eunate Valdaliso Díez
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Alexandre Bosch Martínez
AECC Predoctoral Felow -
So Young Lee
Members
Latest Publications
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
Factor-inhibiting HIF (FIH) promotes lung cancer
García-del Río, AGD; Prieto-Fernández, E; Egia-Mendikute, L; Antonana-Vildosola, A; Jimenez-Lasheras, B; Lee, SY; Barreira-Manrique, A; Zanetti, SR; de Blas, A; Velasco-Beltrán, P; Bosch, A; ...
JCI INSIGHT
2023-10-23
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
The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function
Foskolou, IP; Cunha, PP; Sanchez-Lopez, E; Minogue, EA; Nicolet, BP; Guislain, A; Jorgensen, C; Kostidis, S; Zandhuis, ND; Barbieri, L; Bargiela, D; Nathanael, D; Tyrakis, PA; Palazon, A; Giera, ...
CELL REPORTS
2023-09-26
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
Enabling CAR-T cells for solid tumors: Rage against the suppressive tumor microenvironment
Antoñana-Vildosola, A; Zanetti, SR; Palazon, A; Aranda, F; Berraondo, P; Galluzzi, L;
ADOPTIVE CELL TRANSFER
2022-01-01
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
Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment
Prieto-Fernandez, E; Egia-Mendikute, L; Bosch, A; del Río, AG; Jimenez-Lasheras, B; Antoñana-Vildosola, A; Lee, SY; Palazon, A;
FRONTIERS IN IMMUNOLOGY
2020-09-30