Scientific contributions
- WW-domains, protein signaling scaffolds and model systems of folding and amyloid formation. (Nature 1996, Nature Structural & Molecular Biology 2000, PNAS 2001, 2014, 2015, JACS Au 2024).
- Defined a phosphorylation-dependent mechanism that labels SMADs, first for activation and then for degradation (Cell 2009, Mol. Cell 2009, Genes and Dev, 2011, Structure 2012).
- Identified novel DNA motifs for SMAD proteins (Nature Communications, 2017).
- DNA recognition by the pioneer maternal pioneer factor FoxH1 (Nature Communications, 2022)
- Determined the molecular basis for distinct roles of SMAD2 and SMAD3 in the regulation of progenitor differentiation genes. This result challenges an erroneous view that had prevailed in the field for two decades that SMAD2 does not interact with DNA (Genes and Dev, 2019).
- Elucidated the rules that define the different composition of SMAD complexes in BMP and TGFβ pathways (Computational and Structural Biotechnology Journal 2021).
- Characterized the conformational landscape of full-length SMAD proteins using an integrative approach (Computational and Structural Biotechnology Journal 2021).
- TGF-β and RAS jointly unmask primed enhancers to drive metastasis. Role of RREB1 and SMAD4 in chromatin remodeling (Cell, 2024)
- Peptide analogues with therapeutic properties (ChemBioChem 2011, Angewandte Chemie 2012, Scientific reports 2016, ACS omega 2020, Nature Communications 2021, CSBJ 2022, Communications Chemistry 2023 ).
- First description of a closed conformation in p38α that modulates its kinase activity and is regulated by redox changes in the cell. Complex structures with 2 compounds (Nature Communications 2023 (I), Nature Communications 2023 (II))
- Compounds that interact with SMAD proteins and prevent the formation of SMAD complexes.
- Identification of markers for recurrence in Endometrial cancer using machine learning.
Last five years highlights
2024
TGF-β and RAS jointly unmask primed enhancers to drive metastasis
Jun Ho Lee, Francisco J. Sánchez-Rivera, Lan He, Harihar Basnet, Fei Xavier Chen, Elena Spina, Liangji Li, Carles Torner, Jason E. Chan, Dig Vijay Kumar Yarlagadda, Jin Suk Park, Carleigh Sussman, Charles M. Rudin, Scott W. Lowe, Tuomas Tammela, Maria J. Macias, Richard P. Koche, Joan Massagué
2024
De Novo Engineering of Pd-Metalloproteins and Their Use as Intracellular Catalysts
Soraya Learte-Aymamí, Laura Martínez-Castro, Carmen González-González, Miriam Condeminas, Pau Martin-Malpartida, María Tomás-Gamasa, Sandra Baúlde, José R Couceiro, Jean-Didier Maréchal, Maria J Macias, José L Mascareñas, M Eugenio Vázquez
2024
AI is a viable alternative to high throughput screening: a 318-target study.
Atomwise AIMS Program (Consortium)
2024
TPPU_DSF: A web application to calculate thermodynamic parameters using DSF data
Pau Martin-Malpartida, Carles Torner, Aurora Martinez, Maria J Macias
2024
Overcoming challenges in structural biology with integrative approaches and nanobody-derived technologies
Miriam Condeminas, Maria J Macias
2023
Structural basis of a redox-dependent conformational switch that regulates the stress kinase p38α
Joan Pous, Blazej Baginski, Pau Martin-Malpartida, Lorena González, Margherita Scarpa, Eric Aragon, Lidia Ruiz, Rebeca A Mees, Javier Iglesias-Fernández, Modesto Orozco, Angel R Nebreda, Maria J Macias
2023
Characterization of p38α autophosphorylation inhibitors that target the non-canonical activation pathway
Lorena González, Lucía Díaz, Joan Pous, Blazej Baginski, Anna Duran-Corbera, Margherita Scarpa, Isabelle Brun-Heath, Ana Igea, Pau Martin-Malpartida, Lidia Ruiz, Chiara Pallara, Mauricio Esguerra, Francesco Colizzi, Cristina Mayor-Ruiz, Ricardo M Biondi, Robert Soliva, Maria J Macias, Modesto Orozco, Angel R Nebreda
2022
Molecular basis for DNA recognition by the maternal pioneer transcription factor FoxH1
Radoslaw Pluta, Eric Aragon, Nicholas Prescott, Blazej Baginski, Lidia Ruiz, Rebeca A Mees, Julia Flood, Pau Martin-Malpartida, Joan Massague, Yael David, María J. Macías
2022
Controlling oncogenic KRAS signaling pathways with a Palladium-responsive peptide
Soraya Learte-Aymamí, Pau Martin-Malpartida, Lorena Roldán-Martín, Giuseppe Sciortino, José R. Couceiro, Jean-Didier Maréchal, Maria J. Macias, José L. Mascareñas and M. Eugenio Vázquez
2022
HTSDSF explorer, a novel tool to analyze high-throughput DSF screenings
Pau Martin-Malpartida, Emil Hausvik, Jarl Underhaug, Carles Torner, Aurora Martinez, Maria J Macias
2021
Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease
Álvaro Rol, Toni Todorovski, Pau Martin-Malpartida, Anna Escolà, Elena Gonzalez-Rey, Eric Aragón, Xavier Verdaguer, Mariona Vallès-Miret, Josep Farrera-Sinfreu, Eduard Puig, Jimena Fernández-Carneado, Berta Ponsati, Mario Delgado, Antoni Riera, Maria J Macias
2021
Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes
Lidia Ruiz, Zuzanna Kaczmarska, Tiago Gomes, Eric Aragón, Carles Torner, Regina Freier, Blazej Baginski, Pau Martin-Malpartida, Natàlia de Martin Garrido, José A Márquez, Tiago N Cordeiro, Radoslaw Pluta, Maria J Macias
2021
Conformational landscape of multidomain SMAD proteins
Tiago Gomes , Pau Martin-Malpartida , Lidia Ruiz, Eric Aragón, Tiago N. Cordeiro*, Maria J. Macias*
2021
Structures of the germline-specific Deadhead and Thioredoxin T proteins from Drosophila melanogaster reveal unique features among Thioredoxins
Regina Freier, Eric Aragón, Błażej Bagiński, Radoslaw Pluta, Pau Martin-Malpartida, Lidia Ruiz, Miriam Condeminas, Cayetano Gonzalez, Maria J Macias
Funding
- Ministerio de Ciencia e Innovación PID2021-122909NB-I00 (2022-2026). SMAD complexes with a functional role in development and cancer progression, as PI. Funded by the Funded by MCIN/AEI/10.13039/501100011033 and the European Regional Development Fund (ERDF).
- Ministerio de Ciencia e Innovación, PDC_2021-121162-I00 (two years). Targeting the SMAD4 transcription factor for drug discovery: applications in cancer and rare diseases, as PI. Funded by MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU”/PRTR”.
- Ministerio de Ciencia e Innovación BFU2017-82675-P (2017-2021, extended up to September 2022). Deciphering the interaction sites of SMAD proteins with cofactors using high resolution structural biology, as PI. Funded by the Funded by MCIN/AEI/10.13039/501100011033 and the European Regional Development Fund (ERDF).
- CaixaImpulse in Health Innovation, 2024. Validation of a new methodology to identify endometrial cancer patients at risk of relapse.
- Knowledge Industry Programme Producte 2023. Drugs4RDs -Novel therapeutic strategies against rare diseases.
- Complementary Plan for Biotechnology – ScreenTech grant 2023 for drug discovery, N9094-G4SMAD
- H2020-SwafS-2019-1, 873134, (2020-2023) CALIPER Linking research and innovation for gender equality, as Researcher.
- Marató de TV3, Genomic indicators for the prediction of recurrence and metastasis in Endometrial Cancer (2020-2023). Two partners: Gynecological oncology, Hospital Sant Pau and our laboratory, as PI of our subproject.
- Severo Ochoa award to IRB Barcelona. (2020-2025, 2015-2020 and 2011-2015), “participation as selected researcher” twice.
- AGAUR, Title: SGR consolidated,2021 SGR 00866, as PI and coordinator
- Contracts with Industry and other institutions: Apeptico, BCN peptides, GP Pharm, Fresenius Kabi, INSUD Pharma, and Slack, and several CIBER projects, with Atomwise AIMS Program to validate AI drug discovery predictions.
- In addition to these projects, during the last five years, our lab has secured (1 FPU, 2 FI, 1 FPI, 2 Maria Skłodowska-Curie) predoctoral and postdoctoral contracts
Given the pivotal role of TGF-β in tumor progression and rare diseases, this pathway is an attractive target for cancer therapy. We are exploring the possibility to target this system thanks to the EU-OPENSCREEN-DRIVE, EU-OPENSCREEN-Chemistry and CANSERV funded projects