Klaudia Sobczak
Klaudia Sobczak
DOCTORAL CANDIDATE
MSCA-ITN Fellow
MSCA-ITN Fellow
Cancer Glycoimmunology Lab & Chemical Glycobiology Lab
Email: ksobczak@cicbiogune.es
Phone: 4225 / 944 061 304
Address: Bizkaia Science and Technology Park, building 801A, Derio (Bizkaia)

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.

Latest Publications

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

2022-12-23

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

N-Linked Glycosylation Regulates CD22 Organization and Function

Wasim, L; Buhari, FHM; Yoganathan, M; Sicard, T; Ereño-Orbea, J; Julien, JP; Treanor, B;

Frontiers in Immunology

2019-04-04

Molecular Basis of Unusually High Neutralization Resistance in Tier 3 HIV-1 Strain 253-11

Moyo, T; Ereño-Orbea, J; Jacob, RA; Pavillet, CE; Kariuki, SM; Tangie, EN; Julien, JP; Dorfman, JR;

Journal of Virology

2018-07-01

Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques

Ereño-Orbea, J; Sicard, T; Cui, H; Akula, I; Julien, JP;

Jove-Journal of Visualized Experiments

2018-07-01

Crystal structure of cystathionine β-synthase from honeybee Apis mellifera

Giménez-Mascarell, P; Majtan, T; Oyenarte, I; Ereño-Orbea, J; Majtan, J; Klaudiny, J; Kraus, JP; Martínez-Cruz, LA;

JOURNAL OF STRUCTURAL BIOLOGY

2018-04-01

Structural Basis of Enhanced Crystallizability Induced by a Molecular Chaperone for Antibody Antigen-Binding Fragments

Ereño-Orbea, J; Sicard, T; Cui, H; Carson, J; Hermans, P; Julien, JP;

JOURNAL OF MOLECULAR BIOLOGY

2018-02-02

Molecular basis of human CD22 function and therapeutic targeting

Ereño-Orbea, J; Sicard, T; Cui, H; Mazhab-Jafari, MT; Benlekbir, S; Guarné, A; Rubinstein, JL; Julien, JP;

Nature Communications

2017-10-02

The Chemical Glycobiology Lab is actively engaged in extensive multidisciplinary studies on diverse glycan-lectin systems related to health and disease. This collaborative research involves Senior (Jimenez-Barbero, Ardá, Ereño-Orbea, Unione) and Emerging Scientists (Gimeno), along with Specialists, Technicians, Postdoctoral associates, and Doctoral candidates.

Using a combination of diverse and synergic methodologies, including chemical synthesis, protein biochemistry and molecular biology, biophysics (ITC, BLI), molecular modelling, and structural biology (X-Ray crystallography and CryoEM), with special emphasis on NMR spectroscopy, the Chemical Glycobiology lab investigates the interactions of glycans related to immune responses, from cancer to bacterial and viral infections.

Indeed, glycans, prevalent on mammalian cells and in the extracellular matrix, collectively form the glycocalyx, impacting physical properties, regulating protein function, and acting as ligands for lectins. Dysregulation of glycosyltransferases results in tumor-associated carbohydrate antigens (TACAs), unique to tumor cells. While TACAs are recognized therapeutic targets, their low immunogenicity presents a challenge for T-cell-dependent immune responses crucial in cancer therapy. TACAs play a crucial role in modulating immune responses within the tumor microenvironment through interactions with lectins. Similar interactions are observed in bacterial and viral-mediated infectious events.

From the application side, the focus is on structure-based drug and vaccine design, collaborating with research groups and pharmaceutical companies worldwide, investigating lectin-glycan and antibody-glycan molecular recognition processes. Additionally, from the basic perspective, we explore the conformational properties of glycans, specially the glycosyl oxocarbenium cations, key intermediates in synthesis and cleavage, and examine the presentation and dynamic properties of glycans designed for specific geometrical shapes.

In parallel, the laboratory continuously develops cutting-edge NMR-based techniques. Special emphasis is placed on the use of stable isotopes (13C, 19F) to push the boundaries of NMR applications. These advancements are vital for understanding the pivotal roles of glycans in their interactions with receptors, influencing biological responses associated with health or disease.

Specific areas and research lines include:

  • • Interactions of glycans with galectins and C-type lectins, overseen by Dr. Ana Ardá.
  • • Recognition of sialic acids by Siglecs and their role as glyco-immune checkpoints, led by Dr. June Ereño-Orbea.
  • • Attachment of glycans to influenza virus proteins and other pathogens, investigating their impact on infections, directed by Dr. Luca Unione.
  • • Analysis of proteoglycans and the functional landscape of glycosylation in cancer, spearheaded by Dr. Ana Gimeno.
Latest Publications

Dissecting the Conformational Stability of a Glycan Hairpin

Yadav, N; Djalali, S; Poveda, A; Ricardo, MG; Seeberger, PH; Jiménez-Barbero, J; Delbianco, M;

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

2024-02-20

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

Evolution of human H3N2 influenza virus receptor specificity has substantially expanded the receptor-binding domain site

Thompson, AJ; Wu, NC; Canales, A; Kikuchi, C; Zhu, XY; de Toro, BF; Cañada, FJ; Worth, C; Wang, SY; Mcbride, R; Peng, WJ; Nycholat, CM; Jiménez-Barbero, J; Wilson, IA; Paulson, JC;

CELL HOST & MICROBE

2024-02-14

Strategy for the Enzymatic Acylation of the Apple Flavonoid Phloretin Based on Prior α-Glucosylation

Gonzalez-Alfonso, JL; Alonso, C; Poveda, A; Ubiparip, Z; Ballesteros, AO; Desmet, T; Jiménez-Barbero, J; Coderch, L; Plou, FJ;

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

2024-02-13

The impact of glycosylation on the structure, function, and interactions of CD14.

Quintana, Jon Imanol; Delgado, Sandra; Rabano, Miriam; Azkargorta, Mikel; Florencio-Zabaleta, Mirane; Unione, Luca; Vivanco, Maria dM; Elortza, Felix; Jimenez-Barbero, Jesus; Arda, Ana;

Glycobiology

2024-01-16

Illuminating a Solvent-Dependent Hierarchy for Aromatic CH/π Complexes with Dynamic Covalent Glyco-Balances

Díaz-Casado, L; Villacampa, A; Corzana, F; Jiménez-Barbero, J; Gómez, AM; Santana, AG; Asensio, JL;

JACS AU

2024-01-02

Krylov, Vadim B; Gomez-Redondo, Marcos; Solovev, Arsenii S; Yashunsky, Dmitry V; Brown, Alistair J P; Stappers, Mark H T; Gow, Neil A R; Arda, Ana; Jimenez-Barbero, Jesus; Nifantiev, Nikolay ...

Cell surface (Amsterdam, Netherlands)

2023-12-15

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

Synthesis of a glycan hairpin

Fittolani, G; Tyrikos-Ergas, T; Poveda, A; Yu, Y; Yadav, N; Seeberger, PH; Jiménez-Barbero, J; Delbianco, M;

NATURE CHEMISTRY

2023-07-03

Total Synthesis and Structural Studies of Zwitterionic Bacteroides fragilis Polysaccharide A1 Fragments

Wang, Z; Poveda, A; Zhang, QJ; Unione, L; Overkleeft, HS; van der Marel, GA; Jesús, JB; Codée, JDC;

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

2023-06-13

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

KR-12 Derivatives Endow Nanocellulose with Antibacterial and Anti-Inflammatory Properties: Role of Conjugation Chemistry

Blasi-Romero, A; Angström, M; Franconetti, A; Muhammad, T; Jiménez-Barbero, J; Göransson, U; Palo-Nieto, C; Ferraz, N;

ACS APPLIED MATERIALS & INTERFACES

2023-05-11

Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms

Siebert, HC; Eckert, T; Bhunia, A; Klatte, N; Mohri, M; Siebert, S; Kozarova, A; Hudson, JW; Zhang, RY; Zhang, N; Li, L; Gousias, K; Kanakis, D; Yan, MD; Jiménez-Barbero, J; Kozár, T; Nifantiev, ...

BIOMEDICINES

2023-05-11

Molecular Recognition of Glycan-Bearing Glycomacromolecules Presented at Membrane Surfaces by Lectins: An NMR View

Lete, MG; Hoffmann, M; Schomann, N; Martínez-Castillo, A; Peccati, F; Konietzny, PB; Delgado, S; Snyder, NL; Jiménez-Oses, G; Abrescia, NGA; Ardá, A; Hartmann, L; Jiménez-Barbero, J;

ACS OMEGA

2023-05-03

SARS-CoV-2 Spike N-Terminal Domain Engages 9-O-Acetylated?2-8-Linked Sialic Acids

Tomris, I; Unione, L; Nguyen, L; Zaree, P; Bouwman, KM; Liu, L; Li, ZS; Fok, JA; Carrasco, MR; van der Woude, R; Kimpel, ALM; Linthorst, MW; Kilavuzoglu, SE; Verpalen, ECJM; Caniels, TG; Sanders, ...

ACS CHEMICAL BIOLOGY

2023-04-27

Highly Diastereoselective Multicomponent Synthesis of Spirocyclopropyl Oxindoles Enabled by Rare-Earth Metal Salts

Tallarida, MA; Olivito, F; Navo, CD; Algieri, V; Jiritano, A; Costanzo, P; Poveda, A; Moure, MJ; Jiménez-Barbero, J; Maiuolo, L; Jiménez-Osés, G; De Nino, A;

ORGANIC LETTERS

2023-04-26

Development of synthetic, self-adjuvanting, and self-assembling anticancer vaccines based on a minimal saponin adjuvant and the tumor-associated MUC1 antigen

Pifferi, C; Aguinagalde, L; Ruiz-de-Angulo, A; Sacristán, N; Baschirotto, PT; Poveda, A; Jiménez-Barbero, J; Anguita, J; Fernández-Tejada, A;

CHEMICAL SCIENCE

2023-03-01

Biomimetic Tweezers for N-Glycans: Selective Recognition of the Core GlcNAc2 Disaccharide of the Sialylglycopeptide SGP

Milanesi, F; Unione, L; Ardá, A; Nativi, C; Jiménez-Barbero, J; Roelens, S; Francesconi, O;

CHEMISTRY-A EUROPEAN JOURNAL

2023-02-24

New Glucosamine-Based TLR4 Agonists: Design, Synthesis, Mechanism of Action, and In Vivo Activity as Vaccine Adjuvants

Romerio, A; Gotri, N; Franco, AR; Artusa, V; Shaik, MM; Pasco, ST; Atxabal, U; Matamoros-Recio, A; Mínguez-Toral, M; Zalamea, JD; Franconetti, A; Abrescia, NGA; Jimenez-Barbero, J; Anguita, ...

JOURNAL OF MEDICINAL CHEMISTRY

2023-02-23

Revealing the Specificity of Human H1 Influenza A Viruses to Complex N-Glycans

Canales, A; Sastre, J; Orduña, JM; Spruit, CM; Pérez-Castells, J; Domínguez, G; Bouwman, KM; van der Woude, R; Cañada, FJ; Nycholat, CM; Paulson, JC; Boons, GJ; Jiménez-Barbero, J; de Vries, ...

JACS AU

2023-02-17