Myriad gene expression changes occur when a macrophage is infected with a pathogen such as Mycobacterium tuberculosis (Mtb). Notably, the macrophage upregulates various innate immune molecules to activate cellular defense mechanisms and promote destruction of the bacterium. At the same time, Mtb induces another set of gene expression changes in order to subvert the innate immune response and set up a replicative niche inside the macrophage. My interests lie in understanding the precise spatial-temporal resolution of RNA processing events in Mtb infected macrophages during early infection, focusing on the following questions:

  • Are gene expression changes upon Mtb infection regulated post-transcriptionally (i.e. at the level of pre-mRNA splicing, mRNA release from chromatin, or mRNA export)?
  • Does Mtb hijack normal post-transcriptional RNA processing events in order to promote its survival in the macrophage?
  • Are Mtb-induced changes dependent on the ESX-1 secretion system and can we implicate any specific bacterial gene products?

Working alongside Dr. Robert Watson, my group will work to understand how regulation of RNA metabolism can influence early stages of Mtb pathogenesis, with the eventual goal of modulating said pathways in order to control Mtb infection.