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Gene expression and genetic stability in adult stem cells

Adult stem cells (aSC) are crucial for the maintenance of organ homeostasis throughout life. To understand how stem cells control the processes of self-renewal and differentiation, we focus on several related areas, working mainly with murine and human mesenchymal stem cells (MSC) and cardiac progenitor cells (CPC). In relation to the regulation of stem cell gene expression programs, we are studying several microRNAs (miRNAs) and some coding genes (cDNAs) as potential regulators of self-renewal, senescence and differentiation. We are currently carrying out in vitro studies to evaluate the putative roles of these miRNAs and identify their target genes, and we have started a program to generate specific mouse models for in vivo analyses. In a related project, we are investigating the putative role in cardiac wound healing played by the complement factors C3a and C5a expressed by different cell types (macrophages, multipotent cells and cardiomyocytes).

We are also interested in the mechanism of genome repair in relation to organism aging. As they accumulate damage, impaired aSC function can lead to ill health, and the genetic health of aSC is therefore essential to prevent disease, delay aging and counteract tissue damage. Our studies in this area currently center on the role of polymerase µ in DNA repair, aging, tumor suppression, and the maintenance of hematopoietic stem cells. We are also investigating the role of cell culture associated oxidative stress in the promotion of genetic instability and senescence in aSC, a critical concern for the further development of cell therapy.

Antonio Bernad
  • Antonio Bernad Miana
  • Platform Director
  • Ext.3300

Antonio Bernad Miana studied Chemical Sciences at the Universidad de Zaragoza and moved to the Universidad Autónoma de Madrid to specialize in Biochemistry and Molecular Biology (1980-84). He went on to complete his PhD (1985-89) at the Centro de Biología Molecular Severo Ochoa (Madrid) under the supervision of Margarita Salas and Luis Blanco. From 1990 to 1993 he worked as a Senior Researcher in the Department of Biological Effects at the Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) in Madrid, where he developed techniques for somatic gene transfer to hematopoieitc stem cells. In 1993 he was an invited researcher at the Center for Blood Research at Harvard Medical School, after which, in 1994, he joined the Centro Nacional de Biotecnología (CNB) in Madrid as a CSIC Científico Titular. At the CNB, first in the Department of Molecular Biology and later in the Department of Immunology and Oncology, he built and directed a research team focused on the biology of hematopoietic and mesechymal stem cells and their use in tissue engineering. In 2006 he was promoted to Profesor de Investigación, the highest category for researchers in the CSIC. In 2007 he moved his research group to the CNIC.