Raúl's research career is focused on the development of genome engineering tools broadly applicable to studying and treating human genetic diseases. Delivery of gene editing tools is perhaps one of the key barriers to widespread use of the genome editing technologies. He has been involved in several research projects to engineer viral delivery systems that can be combined with genetic editing nucleases such as CRISPR/Cas9.
Raúl received his Ph.D. under the supervision of Dr. Ramirez at the viral vector group (CNIC). During that period, he engineered novel viral systems for gene delivery (AAV, AdV & LV) improving their potential as tools for basic and translational research. Particularly, he developed a system that promotes the target integration of any transgene in a pre-designed genomic region. Most importantly, an optimization of that original system has been granted with a worldwide patent (WO2015078999), and the technology has been licensed to a biotechnology company (VIVEBiotech). During his Ph.D. training he also participated in several collaborative projects including a study developed with the CNIO Molecular Cytogenetics’ lab. In this project, they harness the CRISPR/Cas9 system to efficiently recreate cancer related chromosomal rearrangements in human cellular models. This approach paves the way to interrogate the function of cancer initiation events in a wild type genomic context.
His long-term goal is to develop robust engineering strategies for studying human genetic diseases. In this pursuit, he works in the elucidation of the mechanisms underlying impairment in speech development. Specifically, he studied the role of chromosomal rearrangements in the modification of enhancer and promoter regions. He developed CRISPR tools to modify enhancer regions in human induced pluripotent stem cells. In 2016, he was awarded by the Canon Foundation to develop Recombinant Sendai vectors to transfer CRISPR/Cas9 system efficiently (Dr.Fusaki lab, Tokio). That system was tested in human hematopoietic cells. In 2017, Raúl was awarded with an international award from Lady Tata Memorial Trust to join Dr. Menendez lab (IJC, Barcelona) as a senior postdoctoral researcher. He are leading a project to mimic the initial chromosomal rearrangements and ontogeny found in pre-natal lymphoid leukemia. I have also collaborated in the discovery of new therapeutic targets in pre-natal leukemia patients (AECC fellowship 2017-2020).
During all this period, he has collaborated in many researcher projects, published more than 50 peer-reviewed articles (h-index 21) and filled 2 patents.
1.- A faecal microbiota signature with high specificity for pancreatic cancer. Kartal E, et al., Gut. 2022 Jul;71(7):1359-1372. doi: 10.1136/gutjnl-2021-324755.
2.- CRISPR Approaches for the Diagnosis of Human Diseases. Puig-Serra P, et al., IJMS 2022 Feb 3;23(3):1757. doi: 10.3390/ijms23031757.
3.- A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL. Zanetti SR, et al., Mol. Ther. 2022 Feb 2;30(2):550-563. doi: 10.1016/j.ymthe.2021.08.033.
4.- Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Garcia-Silva S, et al., Nat Cancer. 2021 Dec;2(12):1387-1405. doi: 10.1038/s43018-021-00272-y
5.- Integrative methylome-transcriptome analysis unravels cancer cell vulnerabilities in infant MLL-rearranged B cell acute lymphoblastic leukemia. Tejedor JR, et al., J Clin Invest. 2021 Jul 1;131(13):e138833. doi: 10.1172/JCI138833
6.- In vivo CRISPR/Cas9 targeting of fusion oncogenes for selective elimination of cancer cells. Martinez-Lage M, et al., Nat Commun. 2020 Oct 8;11(1):5060. doi: 10.1038/s41467-020-18875-x
7.- Robustness of Catalytically Dead Cas9 Activators in Human Pluripotent and Mesenchymal Stem Cells. Petazzi P, et al., Mol Ther Nucleic Acids. 2020 Jun 5;20:196-204. doi: 10.1016/j.omtn.2020.02.009
8.- Clinically Relevant Correction of Recessive Dystrophic Epidermolysis Bullosa by Dual sgRNA CRISPR/Cas9-Mediated Gene Editing. Bonafont J, et al., Mol Ther. 2019 May 8;27(5):986-998. doi:10.1016/j.ymthe.2019.03.007. Epub 2019 Mar 15
9.- NHEJ-Mediated Repair of CRISPR-Cas9-Induced DNA Breaks Efficiently Corrects Mutations in HSPCs from Patients with Fanconi Anemia. Roman-Rodriguez FJ, et al., Cell Stem Cell. 2019 Nov 7;25(5):607-621.e7. doi: 10.1016/j.stem.2019.08.016
10.- Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor modeling. Oldrini B, et al., Nat Commun. 2018 Apr 13;9(1):1466. doi: 10.1038/s41467-018-03731-w
11.- Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using CRISPR/Cas9. Torres-Ruiz R, et al., Stem Cell Reports. 2017 May 9;8(5):1408-1420. doi: 10.1016/j.stemcr.2017.04.014
12.- Engineering human tumour-associated chromosomal translocations with the RNA-guided CRISPR-Cas9 system. Torres R, et al., Nat Commun. 2014 Jun 3;5:3964. doi: 10.1038/ncomms4964
13.- An integration-defective lentivirus-based resource for site-specific targeting of an edited safe-harbour locus in the human genome. Torres R, et al., Gene Ther. 2014 Apr;21(4):343-52. doi: 10.1038/gt.2014.1
14.- Non-integrative lentivirus drives high-frequency cre-mediated cassette exchange in human cells. Torres R, et al., PLoS One.2011;6(5):e19794. doi: 10.1371/journal.pone.0019794. Epub 2011 May 23