Will Bailis, PhD, Assistant Professor, Department of Pathology, University of Pennsylvania, Children’s Hospital of Philadelphia
Metabolic patterning of immune responses
Abstract: Developmental systems call for progenitor cells to divide and differentiate into distinct cell fates. This holds true within the immune system, where the defense against infection, the control of cancer, and the success of vaccines require individual T-cells to expand and give rise to short-lived effectors that kill pathogenic cells and memory cells that provide long-lasting protection. Though these events occur over weeks and months, they are heavily patterned during the initial events following activation, through signaling as well as metabolic rewiring. Thus, early biochemical changes set T-cells down long-term fate trajectories. How “early” and the extent to which this is deterministic remain unresolved questions. We have found that NAD biosynthesis scales with the strength of activating signaling and that single-cell differences in T-cell NAD(H) prior to division can predict the proliferative and differentiation potential of CD8 T-cells in vivo. In this manner, NAD(H) production acts as a conduit connecting metabolism to the biology directed by signal transduction, offering a unifying model for how the early events following activation set T-cell fate potential. This seminar will explore these findings and discuss their implications for novel strategies to engineer and therapeutically modulate immune responses.
The colloquium will feature invited lecturers and bring together metabolism researchers to share ideas, expertise and resources. Visiting lecturers will present a seminar on their work (time and dates will vary) as well as meet with members of the metabolism community.