Inflammation can be induced both by tissue damage and infection and the purpose of this physiological response is to repair damaged tissue and return it to normalcy. Inflammation is also a central component of both autoimmune disease and cancer. During such conditions, however, the inflammatory response is not properly regulated and the response becomes chronic and a component of disease. The “sterile” inflammation induced upon tissue injury has been shown to be due to be partially caused by the release of components from damaged and dying cells. These so-called DAMP (damage associated molecular patterns) molecules have been shown to be ligands of pro-inflammatory receptors such as TLRs and RAGE.
The focus of the research performed in our laboratory is the S100A9 protein, a bona fide DAMP, that binds to and stimulates the pro-inflammatory receptor TLR4. The over all goal of the research performed in our laboratory is to better understand what is the role of this protein in autoimmune disease and cancer. The S100A9 protein is most often co-expressed and forms heterodimers with the S100A8 protein. Current research in the lab aims at defining conditions during which S100A9 is expressed in the absence of S100A8. Further, we are further dissecting the pathway of S100A9-induced stimulation of TLR4. Other projects in the lab investigate the role of S100A9 in cancer, both at the level of the solid tumor itself at the level of metastasis. Through close collaboration with at biotech company, we have available small molecule inhibitors that bind S100A9 and blocks its interaction with RAGE and TLR4. We use these molecules as tools in mouse cancer models to define possible functional roles of S100A9 during tumorigenesis and metastasis.