“Retrotransposon Activation as a Mechanism of Age-associated Sterile Inflammation: Repurposing HIV Drugs to Treat Chronic Diseases of Aging”
John Sedivy has had a long-standing interest in molecular genetics, signaling and cell cycle control. As a postdoc, he developed one of the first methods for targeted homologous recombination, which he subsequently used to construct gene knockouts in somatic cells. In 1995, Dr. Sedivy’s lab isolated a knockout of c-Myc in a rat fibroblast cell line, which led to his career-long interest in this proto-oncogene. 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), which initiated his entry into the field of cellular senescence.
In 2002, Dr. Sedivy’s lab 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, he published the first in vivo quantification of cellular senescence in aging primates.
Dr. Sedivy’s interests subsequently evolved toward the biology of aging, studying whole genome chromatin changes, which recently led to the discovery of the age-associated activation of retrotransposable elements in somatic cells.
He is the P.I. of a grant from the Alzheimer’s Association of America to conduct, in collaboration with Dr. Stephen Salloway and the Butler Hospital, the first trial of the nucleoside reverse transcriptase inhibitor drug Emtriva for the treatment of Alzheimer’s Disease. He has maintained an active research program that has been continuously funded by the NIH for over 30 years, including a MERIT Award from the NIA. Dr. Sedivy has mentored more than 20 graduate students and 20 postdocs, most of whom remain actively engaged in research. I have been closely involved with training and education, serving on more than 50 thesis advisory and examination committees, including as outside reader on PhD exams in the USA, Canada, Sweden, Italy, Netherlands, and Hong-Kong.
We all benefit greatly from a diverse workforce. Throughout his career, and as P.I. of a NIA T32 training grant, he has been committed to the recruitment and mentoring of women scientists, individuals from underrepresented groups, disadvantaged backgrounds and those with disabilities. He has held many leadership roles, most recently, as the Director of the Brown Center on the Biology of Aging. Outside of his institution, he has played an active role in the field of aging, as a founding member and chair of the NIH CMAD study section, 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.