Biography

Dr. Eladio A. Velasco-Sampedro (EAV-S; https://www.scopus.com/authid/detail.uri?authorId=57798202600; https://orcid.org/0000-0002-9682-5589) has focused his scientific career on the Molecular Genetics of inherited disorders. He has worked in several diseases such as Childhood Spinal Muscular Atrophies (PhD thesis, 1996; Extraordinary Doctorate Award, Universidad Autónoma de Madrid), Neurofibromatosis type I, Inherited Ataxias, Darier´s disease and, since 2000, in hereditary breast and ovarian cancer. He has participated in different aspects of the molecular characterization of the responsible genes. His current line of research studies the correlation between aberrant splicing of tumour suppressor genes and genetic susceptibility to cancer. He has developed a new splicing reporter plasmid (pSAD; patent #P201231427 CSIC) that has constituted the backbone of hybrid minigenes of several human disease genes, including breast/ovarian cancer susceptibility genes: BRCA1, BRCA2, ATM, CHEK2, PALB2, RAD51C, RAD51D, TP53, BARD1, as well as MLH1 (Lynch syndrome), COL1A1 (Osteogenesis Imperfecta), SERPINA1 (Alpha-1-antitrypsin deficiency), CHD7 (Charge Syndrome), GRN (Frontotemporal Dementia), UGT1A1 (Gilbert Syndrome) and TRPM4 (colorectal cancer). By these means, the largest minigenes ever reported have been constructed and a vast number of DNA variants (~1000) of the breast cancer genes has been tested. Thus, we have shown that splicing mutations of breast cancer genes are highly frequent. These findings are contributing to clarify the genetic susceptibility spectrum of breast/ovarian cancer and the specific participation of splicing mutations. Under the translational viewpoint, the EAV-S lab has also provided splicing data of +600 DNA variants reported worldwide in breast/ovarian cancer patients.
This functional catalogue of variants contain critical information for their clinical interpretation and Genetic Counselling Units with a view to preventing this group of diseases. By virtue of his expertise in hybrid minigenes, EAV-S was invited to participate in the H2020 BRIDGES grant (Breast Cancer Risk After Diagnostic Gene Sequencing; Coordinator: Peter Devilee, LUMC, The Netherlands), being the Principal Investigator of participant no. 18 .
EAV-S was also involved in the study of the impact of promoter germline mutations of BRCA genes on transcription and their involvement in breast/ovarian carcinogenesis. Promoter regions of cancer-susceptibility genes are under-investigated as they are not routinely screened in genetic testing laboratories. It was found that BRCA2 transcription is highly sensitive to promoter variants causing either over or under expression.
Next years EAV-S plans to study the specific splicing regulation of the non-canonical splice-sites (e.g. GC-donors) and other special exons, such as long exons (BRCA1 and BRCA2 exons 11, PALB2, exons 4 and 5 and BARD1 exon 4) or microexons (e.g. TP53 exon 3), and their roles in health and cancer.
The scientific career of Eladio Velasco is supported by publications in relevant journals of categories Genetics and Heredity, Oncology, Medical Laboratory Technology or Biochemical Research Methods, mainly of the first quartile or decile, such as: Nature Protocols, Clinical Cancer Research, The Journal of Pathology, Clinical Chemistry, PLoS Genetics or Human Molecular Genetics. He has been the principal investigator of 11 Spanish and 1 European projects and has collaborated in at least other 15 grants .