EventDr. Duygu Uçar

Genomic signatures of immune system aging

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel regulatory programs behind these changes, we profiled blood samples from young and old individuals (n=77) using state-of-the-art genomic technologies and analyzed these data using systems immunology methods. First, we described an epigenomic signature of immune system aging, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling. This signature was primarily borne by memory CD8+ T cells, which exhibited an aging-related loss in IL7R activity and IL7 responsiveness. Second, in a bigger cohort (n=130), we studied the impact of sex on immune system aging. Aging has been associated with significant and conserved changes between men and women including reduced activity at loci associated with naïve T cells especially naïve CD8+ T cells and increased activity at loci associated with monocytes and cytotoxic cells (memory CD8+ T and NK cells). Trajectory analyses revealed that aging-related changes are more gradual in women and start later in life (5-6 years delay). Due to these sex-specific aging patterns, immune systems of men and women diverge over time, where old women have more activity at loci associated with adaptive cells and old men have more activity at loci associated with innate cells. Together our multi-faceted data and analyses precisely described the impact of age and sex on human immune system, which is critical towards understanding and battling aging and aging-associated immunodeficiency.

Bio: Bio: Dr. Ucar earned her B.S. degree in Computer Engineering from Bilkent University followed by her Ph.D. in Computer Science from the Ohio State University. She conducted postdoctoral studies at University of Iowa and Stanford University, during which she developed computational methods to discover cell-specific epigenomic patterns from ChIP-seq datasets. In 2013, she launched her laboratory at The Jackson Laboratory for Genomic Medicine (JAX-GM). The overarching goal of her lab is to uncover how epigenomic landscape of human cells -especially immune cells- are remodeled and disrupted with aging and aging-related diseases. She also studies how genetic variants impact epigenomic landscapes of human cells in the context of complex diseases, e.g., Type 2 Diabetes (T2D). Towards this goal, she combines advanced computational techniques with state-of-the art NGS approaches (e.g., ATAC-seq, CITE-seq).