Jeff Smith, PhD
Jeff Smith, PhD, a professor in the Department of Biochemistry and Molecular Genetics, and his lab were recently awarded a five-year, $2.6 million R01 research grant from the NIH – National Institute on Aging, for a project titled “Mechanisms of rDNA instability during aging.”
Aging is the primary risk factor for most chronic diseases, including heart disease, diabetes, cancer, and neurodegenerative conditions. The biological mechanisms underlying aging also overlap with those of chronic diseases, making aging itself an attractive target for interventions that may broadly delay such debilitating conditions as we age. Dr. Smith’s lab utilizes baker’s yeast, Saccharomyces cerevisiae, as a simple genetic and biochemical model for studying aging at the cellular level. They focus on identifying conserved processes that break down with age and then investigate potential interventions that alleviate such defects. Genomic instability is one of these defects that occurs during aging in all organisms, contributing to the increased cancer risk in humans.
The new project investigates how yeast and human cells attempt to maintain stability of a highly conserved and repetitive chromosomal region known as the ribosomal DNA (rDNA), which is especially prone to DNA damage in the form of double-stranded breaks (DSBs). Additional hotspots for aging associated DSBs will be mapped across the entire genome of yeast and human cells using a sequencing method pioneered by Yuh-Hwa Wang, a collaborator in the Department of Biochemistry and Molecular Genetics. When DSBs at the rDNA are improperly repaired in yeast cells, they result in large alterations of rDNA gene copy number that accelerate aging. Dr. Smith’s team will therefore be researching how the yeast cells utilize a newly identified regulatory network of known longevity factors to counteract the age-induced rDNA instability. They will also investigate how analogous factors in human cells regulate rDNA stability and aging, potentially establishing a conserved mechanism that could be therapeutically targeted in the future.
Additional collaborators on the project include Chongzhi Zang, PhD, Todd Stukenberg, PhD, and Larry Mesner, PhD, from the UVA School of Medicine.
Filed Under: Research