My career revolves around the application of in silico tools to address biological questions. My Ph.D. was about the study of the protein structure principles underlying function, a work that I pursued in my stay at the NIH (1993-1997) and the UCL (1997-2000). After joining ICREA, this topic has focused most of my activities (PCB, 2001-2009; IBMB-CSIC, 2009-2012). However, my interests have gradually shifted towards the study of translational problems in biomedicine. In this direction, in 2012, I joined the Vall d'Hebron Institute of Research (VHIR), to enhance the applicability of our work on the pathogenicity of genetic variants, bringing it closer to healthcare stakeholders. Our efforts have recently (2018-2019) gained international recognition after our participation in the prestigious CAGI 5/ENIGMA contest, where we ranked in the second position in the groups' classification.
Our main research aims at understanding the molecular basis of hereditary disease, integrating two complementary aspects: the molecular impact of causative variants and how genetic background regulates the propagation of this impact. At a technical level, to reach our objective, we integrate the results of the most advanced genomic experiments (single-cell, Hi-C, etc.) using state-of-the-art machine learning tools. To enhance the biomedical reach of our research, we work in collaboration with clinical groups from different hospitals. As a result of these efforts, we have recently made significant advances in understanding the functional effect of BRCA1/2 protein variants underlying hereditary breast and ovarian cancers. Finally, mention that we are also devoting an important part of our efforts to the fundamental study of epigenetic processes, to reach a full picture of which phenomena contribute to the generation of phenotype and, more precisely, of clinical phenotype.
– Padilla N, Moles-Fernandez A, Riera C, Montalban G, Özkan S, Ootes L, Bonache S, Diez O, Gutierrez-Enriquez S & de la Cruz X 2019, ‘BRCA1- and BRCA2-specific in silico tools for variant interpretation in the CAGI 5 ENIGMA challenge’, Hum Mutat, 40:1593 – 1611.
– Pappa S, Padilla N, Lacobucci S, Vicioso M, Alvarez de la Campa E, Navarro C, Marcos E, de la Cruz X & Martinez-Balbas MA 2019, ‘PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors‘, P Natl Acad Sci USA , 116:19464 – 19473.
– Marin O, Aguirre J & de la Cruz X 2019, ‘Compensated pathogenic variants in coagulation factors VIII and IX present complex mapping between molecular impact and hemophilia severity’, Sci Rep, 9, 9538.
– Sanchez-Mora C, Soler Artigas M, Garcia-Martinez I, Pagerols M, Rovira P, Richarte V, Corrales M, Fadeuilhe C, Padilla N, de la Cruz X, Franke B, Arias-Vasquez A, Casas M, Ramos-Quiroga J-A & Ribases M 2019, ‘Epigenetic signature for attention-deficit/hyperactivity disorder: identification of miR-26b-5p, miR-185-5p, and miR-191-5p as potential biomarkers in peripheral blood mononuclear cells’, Neuropsychopharmacol, 44:890 – 897.
– Blazquez-Bermejo C, Carreno-Gago L, Molina-Granada D, Aguirre J, Ramon J, Torres-Torronteras J, Cabrera-Perez R, Angel Martin M, Dominguez-Gonzalez C, de la Cruz X, Lombes A, Garcia-Arumi E, Marti R & Camara Y 2019, ‘Increased dNTP pools rescue mtDNA depletion in human POLG-deficient fibroblasts’, Faseb J, 33:7168 – 7179.
– Navio D, Rosell M, Aguirre J, de la Cruz X & Fernandez-Recio J 2019, ‘Structural and Computational Characterization of Disease-Related Mutations Involved in Protein-Protein Interfaces’, Int J Mol Sci, 20(7):1583.
Selected research activities
- Invited to give the Opening Lecture at the IX National Conference BIFI 2019.
- Participated (ranked 2nd) in the 5th Internat. CAGI/ENIGMA challenge for identifying risk variants in breast and ovarian cancer