, in the
Oval Office with President
Donald Trump in 2019 At the
University of North Carolina at Chapel Hill, Sharpless ran a basic science laboratory that utilized genetically engineered mice to study cancer and aging, and was co-founder and co-director of the UNC Lineberger Mouse Phase I Unit. His research focused on how normal cells age and undergo malignant conversion. which was featured on BBC News and other international news agencies for its promise to eventually "measure" human aging. The biomarker was subsequently shown to be a clinical outcome predictor in kidney transplant. The biomarker assay was commercialized by a clinical-phase biotech company called Sapere Bio (formerly HealthSpan Dx), founded by Sharpless and his team. He has published numerous papers that show the role of
p16INK4a in shutting down the stem cells that renew the body's various tissues. He is also one of the founders of
G1 Therapeutics, listed $GTHX under the NASDAQ, which is a clinical-stage biopharmaceutical company developing small-molecule therapies for the treatment of patients with cancer. Extending upon this work, Sharpless' team developed the p16LUC model, a genetically engineered mouse that 'glows' upon activation of the p16INK4a promoter due to insertion of firefly luciferase in place of the endogenous gene. Use of this system revealed the activation of p16INK4a in tissues surrounding nascent tumors, allowing scientists to non-invasively visualize the formation and progression of spontaneous cancers in living animals. Furthermore, this allele has made it feasible to better understand aging toxicology. Specifically, Ned's lab has used the p16LUC allele to understand how low dose toxic exposure over a lifetime can affect the rate of molecular aging. He is also a founder of Sapere Bio (formerly HealthSpan Diagnostics), a clinical-phase biotechnology company measuring
physiologic reserve to improve healthcare. Most recently, Sharpless with
Judith Campisi, PhD, of the
Buck Institute for Research on Aging, and colleagues demonstrated In 2016 how chemotherapy triggers cellular
senescence, a pro-inflammatory stress response, which promotes the adverse effects of chemotherapy as well as cancer relapse and metastasis. Eliminating the senescent cells in mice prevented the side effects. He has also reported on meta-analyses of GWAS studies of aging and disease, identifying the
major histocompatibility complex and the
p16INK4a/ARF loci as the most frequently reported disease associated loci in humans. In 2009, Sharpless and his team were the first to discover altered human INK4/ARF expression as the mechanism for the 9p21.3 genetic risk allele of atherosclerosis. This was first published study identifying the underlying mechanism of 9p21.3, a genetic risk variant with the strongest, and most consistent association with atherosclerosis in multiple, independent, large-scale GWASs (Genome Wide Association Studies). The findings remain to be the most plausible mechanism of 9p21.3 atherosclerosis risk up to this date. In 2010 Sharpless's lab reported the first known human
circular RNA produced from a long non-coding RNA, and linked its expression to alleles strongly associated with risk of atherosclerosis. In 2013 Sharpless and his lab cataloged a large list of circular RNAs in human cell lines and mouse tissues using a whole genome sequencing strategy employing
RNase R digestion. These were identified as highly stable transcripts, and reported the first link between circular RNAs and
ALU Elements. Sharpless coined the term "backsplicing" to refer to the process by which these circular RNAs might be formed. In August 2013, he was appointed director of UNC Lineberger Comprehensive Cancer Center. ==Publications, awards, professional positions and honors==