Biophysics and Biochemistry of Macromolecular Interactions

Group leader
Cesar Martin & Helena Ostolaza
Phone
+34 94 601 8052 / +34 94 601 5538
Address

cesar.martin@ehu.eus

elenaamaya.ostolaza@ehu.eus

Biofisika Institute (CSIC, EHU)
Science Park of the EHU
Barrio Sarriena s/n. 48940 Leioa, Bizkaia (Spain)

Research goal

We are an interdisciplinary research group combining biophysical, cell biology, biochemistry and molecular biology methodologies. Two are our main research focuses are:

  • The study of the molecular mechanisms that underlie protein-protein and protein-membrane interactions, using bacterial toxins as a model system, in particular, the adenylate cyclase toxins, which are essential virulence factors produced by different bacterial pathogens (e.g. Bordetella pertussis, Escherichia coli).
  • Understanding the molecular mechanism that leads to genetic/hereditary hypercholesterolemia and cardiovascular disease. We do translational research by assessing pathogenic variants of LDLR, ApoB-100 and PCSK9 to provide a certain genetic diagnosis of the disease.
Group members
University Lecturer
University Professor
Publications

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Hintze J, Topaktas AB, Madsen TD, Jebari-Benslaiman S, Claridge BH, D'Andrea S, de Haan N, Hansen LH, Baars R, Quittot N, Martin C, Yang Z, Vakhrushev SY, Miller RL, Strickland DK, Hyman B, Fadda E, Schjoldager KT. 

The Ligand Preference of LRP1 is Regulated by O-glycans
Sci Adv. 2026 Jun 5;12(23):eadx9875.
DOI: 10.1126/sciadv.adx9875.

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Apodaka-Biguri M, Simão AL, González-Romero F, Mestre D, Rodrigues PM, Aurrekoetxea I, Gómez-Santos B, Buqué X, Nieva-Zuluaga A, de Gauna MR, Fernandez-Puertas I, Gomez-Jauregui P, Sainz-Ramirez N, Alfaro-Jiménez K, Ortiz-Palma A, Castillero E, Iglesias-Ara A, Mitxelena J, Eriz A, Aransay AM, Lozano JJ, Marin JJG, Izquierdo-Sanchez L, Perugorria MJ, Bujanda L, Banales JM, Martín C, Mosteiro L, Errazti G, Syn WK, Castaño L, Zubiaga AM, Castro RE, Aspichueta P

E2F2 transcription factor promotes a cholestatic MASH phenotype by regulating hepatobiliary metabolism through miR-34a-5p
Hepatology. 2026 May 1;83(5):1231-1247
DOI: 10.1097/HEP.0000000000001461

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Gomez-Larrauri A, Benito-Vicente A, Uribe KB, Martin C, Gomez-Muñoz A

Regulation of Cell Proliferation and Migration by Extracellular Phosphatidic Acid
Biomedicines. 2026 Mar 10;14(3):616.
doi: 10.3390/biomedicines14030616

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Gracia-Rubio I, Benito-Vicente A, Lamiquiz-Moneo I, Bea AM, Marco-Benedí V, Cabrera-Antón E, Martín C, Civeira F, Cenarro A.

Sequencing and functional characterization of SCARB1 variants in subjects with extreme HDL cholesterol levels
J Clin Lipidol. 2026 Feb;20(2):389-401.
doi: 10.1016/j.jacl.2025.11.017

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Mercado-Gómez M, Goikoetxea-Usandizaga N, Giné AE, Merlos Rodrigo MA, Afonso MB, Azkargorta M, Zapata-Pavas LE, Rejano-Gordillo CM, Romero MR, Mendizabal I, Rodrigues PM, Wu H, Rodríguez-Agudo R, Serrano-Maciá M, Olaizola P, Barrenechea-Barrenechea JA, González Recio I, G Fernandez-Barrena M, Overi D, Gaudio E, Schaeper U, Garcia-Longarte S, Yáñez-Bartolomé M, Peña-SanFelix P, Gil-Pitarch C, Lapitz A, Michalkova H, Heger Z, Conter C, Macias RIR, Carracedo A, Bañales J, Moreno V, Lamarca A, Singh R, Delgado TC, Martínez-Cruz LA, Elortza F, Avila MA, Martín C, Tian TV, Macarulla T, Buccella D, Cubero FJ, Calvisi DF, Carpino G, Marin JJG, Rodrigues CMP, Martinez-Chantar ML

Role of CNNM4 in the progression of cholangiocarcinoma: implications for ferroptosis and therapeutic potential
Gut. 2026 Jan 8;75(2):341-352. PMID: 40764063.
doi: 10.1136/gutjnl-2024-333255

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González-Recio I, Goikoetxea-Usandizaga N, Rejano-Gordillo CM, Conter C, Rodríguez Agudo R, Serrano-Maciá M, Zapata-Pavas LE, Peña-Sanfélix P, Azkargorta M, Elortza F, Herranz JM, Guillamon Thiery Á, Guerra-Ruiz AR, Jover R, Galicia-Garcia U, Martín C, Schaeper U, Delgado TC, Díaz-Moreno I, Díaz Quintana A, Buccella D, Nogueiras R, Argemi J, Ávila MA, Gratacós-Ginès J, Iruzubieta P, Pose E, Bataller R, Crespo J, Martínez-Cruz LA, Martínez-Chantar ML

Modulatory effects of CNNM4 on Protein-L-Isoaspartyl-O-Methyltransferase repair function during Alcohol-Induced hepatic damage
Hepatology. 2025 Aug 1;82(2):388-404. Epub 2024 Nov 19. PMID: 39641635; PMCID: PMC12266796.
10.1097/HEP.0000000000001156

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Arrasate A, Lopez-Robles C, Zuazo M, Banos-Mateos S, Martin C, Lamsfus-Calle A, Fertin MJ.

Lentiviral Vectors: From Wild-Type Viruses to Efficient Multi-Functional Delivery Vectors
Int J Mol Sci. 2025 Sep 1;26(17):8497. PMID: 40943418; PMCID: PMC12429303.
10.3390/ijms26178497.

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Gomez-Larrauri A, Benito-Vicente A, Larrea-Sebal A, Martín C, Gomez-Muñoz A

Role of Ceramide Kinase/C1P in the Regulation of Cell Growth and Survival
Int J Mol Sci. 2025 Aug 28;26(17):8374. PMID: 40943293; PMCID: PMC12429069.
10.3390/ijms26178374.

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Gomez-Larrauri A, Larrea-Sebal A, Martín C, Gomez-Muñoz A. 

The critical roles of bioactive sphingolipids in inflammation
J Biol Chem. 2025 Aug;301(8):110475. Epub 2025 Jul 11. PMID: 40653199; PMCID: PMC12340401.
10.1016/j.jbc.2025.110475

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Ostolaza H, Amuategi J

Membrane Interaction Characteristics of the RTX Toxins and the Cholesterol-Dependence of Their Cytolytic/Cytotoxic Activity
Int J Mol Sci. 2024 Mar 8;25(6):3131
doi: 10.3390/ijms25063131

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Alloza-Moral I, Aldekoa-Etxabe A, Tulloch-Navarro R, Fiat-Arriola A, Mar C, Urrechaga E, Ponga C, Artiga-Folch I, Garcia-Bediaga N, Aspichueta P, Martin C, Zarandona-Garai A, Pérez-Fernández S, Arana-Arri E, Triviño JC, Uranga A, España PP, Vandenbroeck-van-Caeckenbergh K

Genetic Analysis and Predictive Modeling of COVID-19 Severity in a Hospital-Based Patient Cohort
Biomolecules. 2025 Mar 10;15(3):393. PMID: 40149929; PMCID: PMC11940120.
10.3390/biom15030393

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Larrea-Sebal A, Sasiain I, Jebari-Benslaiman S, Galicia-Garcia U, Uribe KB, Benito-Vicente A, Gracia-Rubio I, Bediaga-Bañeres H, Arrasate S, Cenarro A, Civeira F, González-Díaz H, Martín C

OptiMo-LDLr: An Integrated In Silico Model with Enhanced Predictive Power for LDL Receptor Variants, Unraveling Hot Spot Pathogenic Residues
Adv Sci (Weinh). 2024 Jan 23:e2305177
doi: 10.1002/advs.202305177

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Jebari-Benslaiman S, Larrea-Sebal A, Benito-Vicente A, Martín C.

Cardiovascular Disease, Atherosclerosis and Familial Hypercholesterolemia: From Molecular Mechanisms Causing Pathogenicity to New Therapeutic Approaches
Int J Mol Sci. 2023 Apr 21;24(8):7659
doi: 10.3390/ijms24087659

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Amuategi J, Alonso R, Ostolaza H

Four Cholesterol-Recognition Motifs in the Pore-Forming and Translocation Domains of Adenylate Cyclase Toxin Are Essential for Invasion of Eukaryotic Cells and Lysis of Erythrocytes
Int J Mol Sci. 2022 Aug 5;23(15):8703
doi: 10.3390/ijms23158703

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Jebari-Benslaiman S, Uribe KB, Benito-Vicente A, Galicia-Garcia U, Larrea-Sebal A, Santin I, Alloza I, Vandenbroeck K, Ostolaza H, Martín C

Boosting Cholesterol Efflux from Foam Cells by Sequential Administration of rHDL to Deliver MicroRNA and to Remove Cholesterol in a Triple-Cell 2D Atherosclerosis Model
Small. 2022 Apr;18(13):e2105915
doi: 10.1002/smll.202105915

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Larrea-Sebal A, Benito-Vicente A, Fernandez-Higuero JA, Jebari-Benslaiman S, Galicia-Garcia U, Uribe KB, Cenarro A, Ostolaza H, Civeira F, Arrasate S, González-Díaz H, Martín C

MLb-LDLr: A Machine Learning Model for Predicting the Pathogenicity of LDLr Missense Variants
JACC Basic Transl Sci. 2021 Nov 22;6(11):815-827
doi: 10.1016/j.jacbts.2021.08.009

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Galicia-Garcia, U., Benito-Vicente, A., Uribe, K.B., Jebari, S., Larrea-Sebal, A., Alonso-Estrada, R., Aguilo-Arce, J., Ostolaza, H., Palacios, L., Martin, C.

Mutation type classification and pathogenicity assignment of sixteen missense variants located in the EGF-precursor homology domain of the LDLR
Sci Rep. 2020 Feb 3;10(1):1727.
DOI: 10.1038/s41598-020-58734-9

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Sánchez-Hernández, R.M., Di Taranto, M.D., Benito-Vicente, A., Uribe, K.B., Lamiquiz-Moneo, I., Larrea-Sebal, A., Jebari, S., Galicia-Garcia, U., Nóvoa, F.J., Boronat, M., Wägner, A.M., Civeira, F., Martín, C., Fortunato, G.

The Arg499His gain-of-function mutation in the C-terminal domain of PCSK9
Atherosclerosis. 2019 Oct:289:162-172.
DOI: 10.1016/j.atherosclerosis.2019.08.020

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Ostolaza, H., González-Bullón, D., Uribe, K.B., Martín, C., Amuategi, J., Fernandez-Martínez, X.

Membrane permeabilization by pore-forming rtx toxins: What kind of lesions do these toxins form?
Toxins (Basel). 2019 Jun; 11(6): 354.
DOI: 10.3390/toxins11060354

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González-Bullón, D., Uribe, K.B., Largo, E., Guembelzu, G., García-Arribas, A.B., Martín, C., Ostolaza, H.

Membrane permeabilization by bordetella adenylate cyclase toxin involves pores of tunable size
Biomolecules. 2019 May 10;9(5):183.
DOI: 10.3390/biom9050183

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Etxaniz, A., González-Bullón, D., Martín, C., Alonso, M.T., Ostolaza, H.

Irreversible versus repairable membrane poration: differences in permeabilization elicited by Bordetella Adenylate Cyclase Toxin and its hemolysin domain in macrophages
FEBS J. 2020 May;287(9):1798-1815.
DOI: 10.1111/febs.15106

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Banerjee, P., Chan, K. C., Tarabocchia, M., Benito-Vicente, A., Alves, A.C., Uribe, K.B., Bourbon, M., Skiba, P.J., Pordy, R., Gipe, D.A., Gaudet, D., Martin, C.

Functional analysis of LDLR (low-density lipoprotein receptor) variants in patient lymphocytes to assess the effect of evinacumab in homozygous familial hypercholesterolemia patients with a spectrum of LDLR activity
Arterioscler Thromb Vasc Biol. 2019 Nov;39(11):2248-2260.
DOI: 10.1161/ATVBAHA.119.313051

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González-Bullón, D., Martín, C., Ostolaza, H.

Characterization of the intrinsic phospholipase A1 activity of bordetella pertussis adenylate cyclase toxin
Toxins (Basel). 2018 Dec 4;10(12):514.
DOI: 10.3390/toxins10120514

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Benito-Vicente, A., Siddiqi, H., Uribe, K.B., Jebari, S., Galicia-Garcia, U., Larrea-Sebal, A., Stef, M., Ostolaza, H., Palacios, L., Martin, C.

p.(Asp47Asn) and p.(Thr62Met): non deleterious LDL receptor missense variants functionally characterized in vitro
Sci Rep. 2018 Nov 9;8(1):16614.
DOI: 10.1038/s41598-018-34715-x

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Benito-Vicente, A., Uribe, K.B., Jebari, S., Galicia-Garcia, U., Ostolaza, H., Martin, C.

Validation of LDLr activity as a tool to improve genetic diagnosis of familial hypercholesterolemia: A retrospective on functional characterization of LDLr variants
Int J Mol Sci. 2018 Jun 5;19(6):1676.
DOI: 10.3390/ijms19061676

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González-Bullón D, Uribe KB, Martín C, Ostolaza H.

Phospholipase A activity of adenylate cyclase toxin mediates translocation of its adenylate cyclase domain.
Proc Natl Acad Sci USA. 2017 Aug 15;114(33):E6784-E6793.
DOI: 10.1073/pnas.1701783114