The INK4b-ARF-INK4a locus encodes three tumor suppressors, p15INK4b, ARF, and p16INK4a. Together, these factors constitute one the most important sources of cancer protection in mammals, equalled in importance only by p53. These tumor suppressors have taken on additional importance in the light of recent evidence that at least one product of the locus, p16INK4a, also contributes to the decline in the replicative potential of self-renewing cells with age. Thus, on the one hand, p16INK4a promotes longevity through its action as a potent tumor suppressor, while on the other hand the increased expression of p16INK4a with age reduces stem and progenitor cell proliferation, ultimately reducing longevity. In other words, p16INK4a appears to balance the need to prevent cancer against the need to sustain regenerative capacity throughout life. These observations suggest the provocative but unproven notion that mammalian aging results in part from the effectiveness of tumor suppressor proteins at preventing cancer.
Our group is investigating the role and molecular regulation of the INK4b-ARF-INK4a locus in the context of selfrenewal, proliferation and aging of hematopoietic stem cells in vitro and in vivo, with planned extension of these studies to cardiac stem cells. In parallel, we are developing tools for the study of the genetic and epigenetic mechanisms that regulate stem cells, and how these unique cells differentiate from a pluripotent to a more restricted state.
Susana Gonzalez obtained her degree in Chemistry and Molecular Biology at the Universidad Autónoma de Madrid in 1994. Susana devoted her thesis work to the study of the molecular mechanisms of influenza virus under the supervision of Dr. Juan Ortin at the Centro Nacional de Biotecnología in Madrid. She received her PhD from the Universidad Autónoma de Madrid.
In 2000, Susana was awarded a postdoctoral fellowship from the Human Frontier Science Program (HFSP) to work in New York with Carlos Cordon-Cardo at the Memorial Sloan-Kettering Cancer Center and Carol Prives at Columbia University. Her work in this period focused on different tumor suppression responses. She subsequently moved to Manuel Serrano’s laboratory at the Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncológicas, in Madrid), where her work helped identify the mechanisms governing the expression of the INK4/ARF locus and the mechanisms through which miRNAs induce heterochromatinization to silence gene promoters. In 2006 Susana was granted an HFSP Career Development Award. She joined the CNIC in 2007.