One major research interest of my laboratory is uncovering protein-protein interactions between host and pathogen proteins. Listeria monocytogenes is opportunistic, food-borne pathogen that can compete with host intestinal microbiota to invade intestinal tissue, replicate in mesenteric lymph nodes, and spread to distal site of infection like the spleen, liver, brain, and placenta. Although most humans can prevent Listeria infections, it can be potentially lethal to immunocompromised individuals and induce spontaneous miscarriages in pregnant women. Being an intracellular pathogen, Listeria has served as a model organism to uncover novel facets of infection biology, cell biology and fundamental microbiology. However, the internalin family of proteins encoded by Listeria, characterized by the presence of a leucine-rich repeat (LRR) domain, remain largely uncharacterized. Therefore, using classical techniques and recently developed proximity ligation assays (PLAs), my lab aims to identify host factors that interact with these proteins using mass spectrometry, and then validate and characterize these interactions using protein biochemistry, cell biology, and genetic manipulation of host and Listeria genomes to uncover the roles of these proteins during infection.
Another major research interest of my laboratory is to understand how plasma membrane (PM) cholesterol plays a role in host-pathogen interactions. As the most abundant lipid species in the mammalian PM, cholesterol has emerged as a common target for bacterial pathogens. Cholesterol plays several critical roles in the structure and function of the PM, such as by maintaining the fluidity, permeability, and integrity of the lipid bilayer through association with membrane receptors, transporters and channels, as well as being involved in diverse signaling pathways. A small pool of cholesterol, termed accessible cholesterol, acts as a signaling molecule to direct the localization of proteins to and within membranes as well as serving as an indicator to total cholesterol levels. We previously demonstrated that depletion of accessible cholesterol is sufficient to block Listeria cell-to-cell spread during infection. However, the underlying mechanisms of this restriction are poorly understood. Moreover, since cholesterol is present in every mammalian membrane, it is likely that pathogens have evolved novel strategies to manipulate this cholesterol to subvert host defenses or to enhance the pathogens virulence. My lab will use molecular and cell biology to identify bacterial proteins that regulate host cholesterol levels and determine the biochemistry carried out by these proteins. Together, these findings will define new roles for cholesterol in host-pathogen interactions.