Xavier de la Cruz Montserrat

Xavier de la Cruz Montserrat

Vall d'Hebron Institut de Recerca

Life & Medical Sciences

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 work has gained international recognition following our participation in the prestigious CAGI contest, where we achieved second place in the group classification for both the Enigma (2018-2019) and ARSA (2023) Challenges, respectively.

Research interests

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. 

Selected publications

- Gracia-Diaz C et al. 2023, 'Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders', Nature Communications, 14, 1.
- Aguirre J, Padilla N, Özkan S, Riera C, Feliubadaló L & de la Cruz X 2023, 'Choosing Variant Interpretation Tools for Clinical Applications: Context Matters', International Journal Of Molecular Sciences, 24, 14, 11872.
- Sheppard SE, Bryant L, Wickramasekara RN, et al. 2023, 'Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice', Science Advances, 9, 10, eade1463.

Selected research activities

- I have coordinated the full development of the Mention in Bioinformatics in the Biomedicine Degree, at the UIC (Universitat Internacional de Catalunya).
- We have introduced our novel prediction methodology to the scientific community through a three-pronged approach: the defense of two PhD theses by Luz Marina Porras (January 2023) and Selen Özkan (December 2023), our participation and subsequent second-place ranking in the ARSA challenge at the international CAGI 6 contest, and dissemination via our dedicated website https://www.biotoclin.org/ATM/.