Our research program involves two broad thematic areas:
We are interested in the role of the extracellular matrix in wound repair processes. An abundant matrix molecule called hyaluronan (HA), is present in a pericellular coat on fibroblasts, epithelial cells, and blood vessels, and appears to be critical for regulating inflammation and fibrosis (scarring) in healing wounds. By using knockout mice lacking one or more of the enzymes that synthesize HA, we are studying how HA coordinates activities of many cell types during skin healing. This research may ultimately provide new ideas for therapy of poorly healing wounds.
We are pursuing a multifaceted approach to improve a type of skin cancer treatment called photodynamic therapy (PDT). PDT has two components: a prodrug (i.e., a porphyrin precursor that is preferentially taken up into malignant cells, where it is converted to porphyrin) and a strong light source that activates the porphyrin inside the cancer cells, producing oxygen free radicals and causing apoptosis. We have found that pretreatment with certain drugs and hormones (including methotrexate, and Vitamin D) can enhance the levels of porphyrin-biosynthetic enzymes in tumor cells, leading to more porphyrin accumulation and more efficient cell killing upon exposure to light. These combination therapies (pretreatment followed by PDT) promise to provide a better therapeutic outcome than PDT alone. We are studying mechanisms in animal tumor models, in order to develop combination PDT regimens and move them into clinical trials.