Our laboratory is interested in understanding the molecular mechanisms of epithelial defense. Critical discoveries from our group include finding that the skin makes natural antibiotic molecules known as Cathelicidins, and more recent discoveries that have defined several critical functions of bacteria that inhabit the skin. Cathelicidins are cationic and amphipathic molecules that inhibit microbial function by targeting microbial membranes. Cathelicidins also stimulate cellular immune defense. Gene targeting and molecular analysis by our laboratory has shown cathelicidins are critical to mammalian immunity and can contribute to human diseases such as acne, rosacea and psoriasis. A direct extension of our work on antimicrobials is our work on the microbiome, cells that have avoided killing by the antimicrobial defense system. We have shown how the normal community of bacteria on human skin contains strain-specific functions that help limit skin inflammation and protect against infection. We are conducting precise molecular characterization of these events and translating this information into human skin therapies. Numerous questions remain in this field and are the subject of ongoing work.
A related interest of our group is the function of tissue Glycosaminoglycans (GAGs). These linear carbohydrate molecules act as immune signaling molecules and co-factors in wound repair. Important growth factors such as FGF-2 and FGF-7 require the GAG Dermatan sulfate in order of bind and activate their signaling receptor. Another GAG, Hyaluronic acid has been observed to be a signal of skin injury, alerting the immune system of danger by activation of pattern recognition receptor TLR-4.