Current Externally-Funded Research Projects
Defining Molecular Mechanisms of Bacterial Pathogenesis: Groundbreaking research from my lab has made foundational contributions to our understanding of how enteric (gut) bacteria such as Salmonella and Shigella colonize the intestine and interact with the host. By exploring the dynamic host-pathogen interactions at mucosal surfaces of the intestine, we have advanced knowledge of epithelial biology and discovered critical insights for the prevention and treatment of infectious diseases. Current work in the lab is focused on understanding the mechanisms of Shigella sp. pathoadaptation.
Innovating Models of Microbial Interactions and Intestinal Inflammation: Studies in my lab first identified a novel role for eukaryotic epithelial cell efflux transporters in maintaining gastrointestinal homeostasis during injury, infection-induced inflammation, or chronic inflammatory diseases such as inflammatory bowel disease (IBD). This work has profound implications for understanding microbial strategies for interacting with the host, and for developing new therapies to combat bacterial drug resistance. To further translate our findings to the clinic, in 2017 we launched Adiso Therapeutics, a clinical-stage biotechnology company committed to creating medicines that treat inflammatory diseases and improve the lives of patients and their families.
Characterizing Neutrophil Migration and Innate Immune Pathways: Pioneering the field of cellular microbiology, my work provided the first evidence that epithelial cells, when they detect pathogenic bacteria, launch a pro-inflammatory response that recruits innate immune cells (neutrophils) across the epithelial mucosal barrier into the lumen of the GI tract. Through this research we have identified new virulence mechanisms and therapeutic strategies for both infectious and non-infectious intestinal disorders.
Exploring the Aging Microbiome and Age-Related Diseases: Recently, my lab has also turned our attention to understanding how gut microbiome dysbiosis contributes to age-related diseases. Working in collaboration with Dr. John Haran, we are investigating how gut microbiome imbalances promote pathogen colonization and implications for the gut-brain axis. Our work is shedding light on how these imbalances impact systemic (whole body) immune responses and contribute to neurodegenerative conditions such as Alzheimer’s disease, particularly focusing on vulnerable elderly populations.
Targeting Microbiome Manipulation and Dietary Interventions for Intestinal Barrier Promotion to Minimize GI-ARS: This arm of our research focuses on developing targeted microbiome therapies and dietary interventions to strengthen the intestinal barrier and minimize gastrointestinal acute radiation syndrome (GI-ARS) caused by nuclear events. By leveraging specific gut bacteria and engineered probiotics to support intestinal epithelial barrier function, we aim to reduce the severity and lethality of GI-ARS. This project involves creating live biotherapeutic products, engineering probiotics like E. coli Nissle 1917, and designing prebiotics-enriched diets to promote barrier-enhancing intestinal bacteria. Supported by an NIH U01 grant with Dr. Vanni Bucci, one of our Microbiology department colleagues, our work has the potential to improve patient survival after exposure to nuclear radiation.