Cancer Center Support Grant

Wake Forest University Health Sciences, Winston-Salem NC

Investigators

Linked publications, trials & patents

Abstract

Epidemiological studies have shown people aging with HIV (PAWH) are more likely to exhibit symptoms of accelerated aging and have increased incidence of non-AIDS-defining cancers (NADCs). Our central hypothesis is that altered redox metabolism driven by HIV infections, cART and aging exert synergistic suppressive pressure on immunometabolism promoting cancer development predominantly in the subgroup of PAWH patients who also display accelerated aging. As redox metabolism is both gender and race-dependent and to serve the catchment area of our Cancer Center, this pilot study focuses on African American males, over the age of 50 and compares four groups: cancer negative (HIV+ and HIV-), and cancer positive (HIV+ and HIV-) (N=10 in each group; cancer: lung and Head and Neck). DNA methylation analysis will be used to calculate the biological age of subjects. scRNA-Seq will be applied to uncover differences in the immune system and redox metabolism between groups. MS-based multi-omics analysis will be applied for analysis of isolated peripheral blood mononuclear cells (PBMC), plasma, and tumor specimens. Blood-based bioenergetic profiles will be collected using high-resolution mitochondrial respirometry of isolated PBMCs. Specialized highly selective chemical probes and methods of analysis developed by our group will be used to characterize and quantify changes in the redox state of tumors, blood cells and plasma fractions.