John Sedivy, has had a long-standing interest in molecular genetics, signaling and cell cycle control. As a postdoc he discovered one of the first methods for targeted homologous recombination, which he subsequently developed for gene targeting of somatic cells. He has maintained an active research program that has been continuously funded for over 25 years, including a MERIT Award from the NIH, focusing mainly on two lines of investigation: the MYC proto-oncogene, and cellular senescence. In 1995 his lab used gene targeting to knock out MYC in a rat fibroblast cell line, and their characterization of these cells led to the discovery that the primary defect appeared to be a reduced rate of rRNA and protein synthesis. This work contributed importantly to the current view of MYC as a major regulator of metabolism. Recently the Sedivy group found that mice with reduced Myc expression have increased longevity and improved healthspan. In their studies of cellular senescence, in 1997 they knocked out the cyclin-dependent kinase inhibitor p21 (CDKN1A gene), a first in normal, nonimmortalized human cells. They subsequently performed a genetic epistasis analysis to show that cellular senescence was regulated in parallel by the p53-p21 and p16-pRb pathways. In 2004 they 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. Their interests subsequently evolved towards the biology of aging, studying whole genome chromatin changes, and culminating in the discovery of the age-associated activation of retrotransposable elements in somatic cells. John has fulfilled major administrative leadership roles in his institution. Outside, he continues to play an active role in the field of aging, such as Editor-in-Chief of the journal Aging Cell, chair of the 2015 Gordon Research Conference on the Biology of Aging, and author of numerous review articles and opinion pieces.
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