Current Research and Scholarly Interests
Our lab studies how immune responses are regulated within injured and infected tissues. We work at the intersection of immunology, structural biology, bioengineering, and microbiology with the goal of develop novel therapeutics to promote wound healing and immune tolerance.
Major areas of investigation include:
The Immunology of Wound Healing
How does the immune system distinguish between injured vs. healing tissue? Why is immune regulation deranged in chronic wounds? One contextual cue that informs local immune responses is the size and amount of hyaluronan (HA), an extracellular matrix polysaccharide abundant in inflamed tissues. At sites of tissue damage, catabolic fragments of hyaluronan function as endogenous “danger signals” and promote immune activation through Toll-like receptor (TLR) signaling. Conversely, at sites of healing, intact hyaluronan provides what we have defined as “tissue integrity signals” that promote immune tolerance through the HA receptor CD44. Current projects under this Aim include learning how cells integrate these signals in injured and healing tissues, investigating the role of regulatory T-cells (Treg) in wound healing, and developing wound dressings that minimize scar formation.
Tissue Matrix and Autoimmunity
Why does inflammation persist at sites of autoimmunity? How do infections and inflammation protect from autoimmunity and asthma (the hygiene hypothesis)? To answer these questions, we are investigating how regulatory T-cell (Treg) behavior is influenced by the extracellular matrix in injured and healing tissues. Current projects under this Aim include studying how anti-inflammatory drugs impact vaccine responses, learning how the mechanical properties of inflamed tissues influence Treg behavior, and developing tolerizing vaccine adjuvants to prevent asthma and autoimmunity.
The Immunology of Microbial Biofilms
How do microbial biofilms suppress local immune responses? The virulence of the major human pathogen Pseudomonas aeruginosa is predicated on its ability to form biofilms. These are networks of host and microbial extracellular matrix organized into slime layers that suppress local immune responses and mediate adhesion and antibiotic resistance. Current projects under this Aim include studying how microbes organize extracellular matrix into biofilms and how these suppress local immune responses. Further, we are devising innovative strategies to prevent chronic infections by targeting microbial biofilms.