Immunity and tolerance are achieved by balancing pro– and anti-inflammatory responses to limit or prevent collateral tissue damage while neutralizing an invading pathogen. At mucosal barriers – which are colonized by diverse communities of commensal microbes and serve to interface the internal physiology of an organism with the ever-changing external environment — fine–tuning opposing immune responses is of even greater relevance. Constant exposure to novel environmental molecules and high concentrations of microbial products that can activate innate immunity increase the risk for persistent inflammatory activation. As a result, complex immune networks operate to contextualize diverse microbial and environmental stimuli. These inputs subsequently shape mucosal immune responses and synergize to preserve mucosal barrier integrity and function. Aberrant immune responses, due to a breakdown in tolerance or defects in barrier maintenance, largely underlie the etiology of chronic mucosal inflammatory disorders.
Our laboratory is committed to understanding how mucosal immune responses are coordinated to maintain homeostasis and respond to microbial infection, barrier disruption, or alterations in commensal microbial diversity — with an emphasis on how these molecular decisions are balanced within the context of host fitness and organ physiology. Our studies are geared toward uncovering pathways with the potential for therapeutic manipulation, focusing on the signals that drive pro— and anti—inflammatory immune responses within each setting. To pursue these goals, we are exploring the molecular mechanisms underlying epithelial barrier repair and investigating the contribution of commensal microbial colonization in these processes.