Inicio Excelencia Severo Ochoa HR EXCELLENCE IN RESEARCH
Epigenetic regulation in cardiac aging and disease

Adult stem cells participate in the natural homeostasis of adult tissues through their ability to both self-renew and differentiate into multiple lineages to regenerate tissue in response to injury signals. During aging, the proliferation and differentiation capacity of tissue-specific stem cells decreases, and they lose their potential to regenerate tissues after damage. PcG-mediated alteration of the epigenetic status of hematopoietic stem cells (HSCs) is proposed as one of the driving forces behind many age-related HSC changes and is often found to be misregulated in human malignancies. Protection of the transcriptional “stemness” network is thus essential for maintenance of a healthy HSC compartment throughout life. A key unanswered question in the field is whether the functional decline in adult stem cells is related to reversible chromatin modifications. We propose that changes to the chromatin state can restore the regenerative capacity of stem cells. To investigate this hypothesis, we are exploring the role of the epigenetic Polycomb-mediated silencing mechanism in stemness maintenance, with particular emphasis on the self-renewal capacity and the microenvironment of HSCs, a key adult stem cell population with diverse regenerative capacities. Understanding molecular mechanisms by which Polycomb members control stem cell fate will provide new insights into hematopoietic stem cell biology and will also increase understanding of neoplastic transformation.

We are also interested in the emerging role of different classes of chromatin regulators and how their dysregulation in the adult heart alters specific gene programs, with subsequent development of major cardiomyopathies. Dilated cardiomyopathy (DCM) represents the third most common cause of heart failure but has been poorly modeled in nonhuman species. We propose that epigenetic remodeling could provide an important means of modulating the transcriptional reprogramming of cardiac gene expression in this condition. Understanding the action of Polycomb factors will allow the development of strategies to control physiological and pathological gene expression.

Susana González
  • González López, Susana
  • Jefe de grupo
  • Ext. 2307

Susana González se licenció en Química y Biología Molecular por la Universidad Autónoma de Madrid en 1994. A continuación, dedicó su tesis al estudio de los mecanismos moleculares del virus de la influenza, bajo la supervisión del Dr. Juan Ortín en el Centro Nacional de Biotecnología, en Madrid. Se doctoró en la Universidad Autónoma de Madrid.

En 2000, Susana recibió una beca posdoctoral de la Human Frontier Science Program (HSFP) para trabajar en el laboratorio del Dr. Cordón-Cardó en el Memorial Sloan-Kettering Cancer Center y de la Dra. Carol Prives en la Columbia University (Nueva York). Durante este tiempo su estudio se centró en las diferentes respuestas de supresores de tumores esenciales. Posteriormente se trasladó al laboratorio de Manuel Serrano, en el Centro Nacional de Investigaciones Oncológicas (CNIO) en Madrid, donde con su trabajo contribuyó a identificar los mecanismos que regulan la expresión de genes frecuentemente mutados en la mayoría de los cánceres humanos, y que se localizan en el locus INK4/ARF, así como, los mecanismos de silenciamiento mediante heterocromatinización de las regiones promotoras por la acción de miRNAs. En 2006 Susana recibió el galardón Career Development Award (Premio al Desarrollo Profesional) del Human Frontier Science Program.

Susana se incorporó al CNIC en 2007.

En 2015, Susana obtuvo una ERC Consolidator Grant.