The mucosal barriers of the body facilitate the arduous task of promoting symbiosis with the resident microbiota while simultaneously preventing microbial invasion and pathogenic inflammation. We aim to uncover not only how tissue-wide homeostasis is achieved but also how its breakdown can be averted to prevent disease by identifying 1) novel molecules, 2) sensory pathways and 3) inter cellular signaling circuits.
1) Translation Immunity
Using genome-wide transcriptomic and translatomic sequencing approaches during inflammation, we have identified a vast array of transcripts with interesting translation dynamics and/or novel protein coding potential. Using a combination of forward and reverse genetic approaches, we aim to delineate the function of these unknown proteins and interrogate their contribution to inflammation and disease.
2) New Sensors of Inflammation
Innate immune cells utilize a plethora of membrane-bound and intracellular sensors that directly recognize microbial invasion to mount an inflammatory response. We have discovered that immune cells express a mechanosensory ion channel that triggers inflammation in response to pulmonary fluctuations in cyclical pressure during mucosal infection and fibrosis. Identification of novel strategies utilized by cells in the tissue microenvironment to instruct immunity is a major direction of our research.
3) Neuro-Epithelial Immunology
We have recently uncovered that enteric neuron expression of pro-inflammatory cytokines is vital for epithelial cell-mediated antimicrobial barrier defense. Understanding how neurons communicate with the entire cellular architecture of the mucosa to influence homeostasis, inflammation and disease is of the foremost interest to our ongoing studies.
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