Assistant Professor
Department of Medicine

Project title: NFκB dynamics in the stimulus specificity of innate immune memory

Alexander Hoffmann, PhD - UCLA
Scott Filler, MD – Lundquist/Harbor-UCLA
Otto Yang, MD - UCLA

Multidisciplinary Expertise:
Molecular biology, innate immunology, bioinformatics, epigenomics

Project Description:
Cytokines and pathogens can reprogram cells of the innate immune system, poising them to be either more inflammatory or less inflammatory, a phenomenon known as innate immune memory. What determines whether a given stimulus will result in potentiated or diminished inflammation is unclear, and the lack of mechanistic insight limits current diagnostic and therapeutic applications of this cellular reprogramming. This proposal explores the hypothesis that dynamic features of the transcription factor NFκB – not if it is activated, but how it is activated – contribute to the stimulus specificity of innate immune memory through the regulation of de novo enhancers that control gene expression. These studies have important implications for understanding how variable and reprogrammable states of the immune system might determine the response to an infection.