PhD Thesis Defense: Hannah Riley Knight (Immuno)

Discovery and Application of Novel Small Molecule Inducers of Trained Immunity

Trained immunity is the epigenetic and metabolic reprogramming of the innate immune system that encodes its memory of previous inflammatory encounters. In most model systems, trained immunity is induced with pathogens, pathogen-derived compounds, or endogenous molecules associated with auto-inflammatory diseases. We sought to demonstrate that inflammation is not required to induce trained immunity, expand the number of known training compounds, and understand the variation in training programs induced by different stimuli.

In this work, we present the first high-throughput screen for compounds that induce training, as well as the first published link between trained immunity and glucocorticoids, a family of commonly used immunosuppressive drugs. We then explore the application of small molecule-induced training in models of cancer, infectious disease, and vaccines.