Basic research in Immunology in the Division of Dermatology is directed towards obtaining a better understanding of the innate mechanisms through which the skin protects against microbial invasion. Work in the Gallo Lab focuses on the role antimicrobial peptides play to kill skin pathogens and trigger cellular immune defense systems.
Our laboratory is interested in understanding the innate molecular mechanisms of epithelial defense and repair. Critical discoveries include finding that the skin makes natural antibiotic molecules known as Cathelicidins. Cathelicidins are cationic and amphipathic molecules that inhibit microbial function by targeting microbial membranes. Cathelicidins also interact with host pattern recognition receptors to stimulate cellular immune defense. Gene targeting and molecular analysis by our laboratory has shown cathelicidins are critical to mammalian immunity and are associated with human disease. For example, patients with atopic dermatitis suppress expression of cathelicidins and defensins and thus are more susceptible to skin infections. Likewise, cathelicidin knock-out mice are susceptible to infection by Group A Streptococcus. A delicate balance is required for proper innate immune function in the skin, as excess antimicrobial peptide expression is also deleterious, and can contribute to diseases such as acne rosacea and psoriasis. 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.
Richard L. Gallo, MD, PhD
PubMed (NCBI) References