Research

Our lab studies how immune responses are regulated within injured and infected tissues with an emphasis on diabetes. We work at the intersection of immunology, structural biology, and microbiology to develop novel therapeutics to promote  immune tolerance, wound healing, and resolution of infection. Major current areas of investigation include:

Extracellular Matrix and Immune Regulation 

IsletsWe are studying how the extracellular matrix contributes to immune regulation at sites of inflammation. In particular, we focus on the extracellular matrix polymer hyaluronan and its influence on the number and function of regulatory T-cells in autoimmune, Type 1 diabetes (T1D).  We have previously reported that the extracellular matrix contributes to the progression of autoimmune insulitis and other autoimmune diseases.  Our current efforts are focused on understanding how the inflamed extracellular matrix influences local antigen presentation and cytolytic killing.

In addition to elucidating fundamental mechanisms of immune regulation, we are working on novel strategies that will prevent T1D and other autoimmune diseases by targeting the extracellular matrix.

Extracellular Matrix and Wound Healing 

Chronic wounds, like tissues under autoimmune attack, are associated with an inflamed extracellular matrix that contributes to immune dysregulation and chronic wounds. We use models of diabetic wound healing to study how the extracellular matrix governs wound healing and local immunity at sites of injury and infection.

Extracellular Matrix and Wound Infections

pf4Pseudomonas aeruginosa is a major pathogen in diabetic wound infections and other settings. The virulence of P. aeruginosa is predicated on its ability to form biofilms. These are networks of host and microbial extracellular matrix that promote colonization, antibiotic resistance, and immune evasion. We are studying how biofilm polymers suppress local immune responses in infected wounds.

Further, we have identified novel roles for bacteriophage in the pathogenesis of wound infections caused by P. aeruginosa. Our research indicates that Pf phage produced by P. aeruginosa act as structural elements in microbial biofilms.  Pf phage also interact with the immune system in ways that subvert clearance of bacterial infections.