Cell cycle control, cellular senescence, telomeres, epigenetics
John Sedivy is recognized for his efforts in mammalian genetics, having developed and pioneered in the late 1980's methods for gene targeting of somatic cells. In 1995 his lab isolated the first viable knockout of c-Myc in a rat fibroblast cell line, which led to his career-long interest in this important oncogene. Recently his group showed that mice with reduced Myc expression have increased longevity and improved health span. In 1997 his lab was the first to achieve a homozygous gene knockout in primary human cells, knocking out the CDKN1A gene (cyclin-dependent kinase inhibitor p21), and showing that this was sufficient to bypass cellular senescence. In 2004 his group developed a reliable single-cell biomarker of telomere-initiated senescence and delineated the signaling pathway between dysfunctional telomeres and the cell cycle. In 2006 they published the first in vivo quantification of cellular senescence in aging primates. More recently the Sedivy lab has been studying chromatin changes during cellular senescence, and though these investigations discovered the activation of retrotransposable elements in aging.