Research in the Radoshevich laboratory is focused on host responses to the cytosolic intracellular pathogens, Listeria monocytogenes and Francisella tularensis. More specifically, we explore changes in the post-translational landscape of the cell following stress or infection. Ubiquitin-like modifications (UBLs) are rapid, reversible and can profoundly alter cell fate and function. Intriguingly, the majority of UBLs are involved in the cellular response to stress, in particular the response to infection, ER-stress and autophagy. We take an interdisciplinary approach combining cutting-edge proteomics with genome editing, biochemistry, cell biology and in vivo infection models to determine fundamental properties and modes of action of understudied ubiquitin-like modifications. We aim to address the central question of how the cell responds to stress by decoding novel networks of covalent protein complexes. We also aim to decipher which bacterial virulence factors hijack and thwart cellular stress responses to illuminate how intracellular pathogens survive and replicate in the host. Most importantly the enzymatic systems that activate, conjugate and ligate UBLs to their protein substrates are promising targets for therapeutic intervention in a number of important human diseases such as cancer, neurodegenerative and autoimmune disorders. It is our hope that by learning about these understudied UBLs as well as important bacterial infections, we could discover potential chinks in the armor of intractable human pathologies.
- Innate immunity
- Host-pathogen interactions