Our research program involves two broad thematic areas, namely: (1) wound healing and (2) skin cancer.
For wound healing, 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.
For skin cancer, 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.
In the Laboratory of Molecular Dermatology, we study two skin disease processes that are very important for medicine and surgery: wound healing and skin cancer. In the case of wound healing, we are interested in how a sort scaffold in the body (the extracellular matrix or ECM), in particular a carbohydrate (sugar) polymer called hyaluronan, can regulateinflammation and fibrosis (scarring) in healing wounds. We aim to understand these processes better and perhaps develop new therapies for poorly healing skin wounds like leg ulcers. For skin cancer, we are trying to improve a new technique called photodynamic therapy (PDT). This treatment has two components: a sensitizing drug (usually delivered as a topical cream) and a strong light source (laser) that activates the drug inside the cancer cells to kill them. PDT works well for cancers close to the surface, but we hope to make PDT work even for thicker and more serious skin cancers. Our laboratory has discovered that when a skin cancer is pre-treated with certain drugs, including methotrexate and Vitamin D, it becomes much more sensitive to PDT. This combination therapy works better than PDT alone in early research studies.We are planning for future clinical trials.
Anand S, Wilson C, Hasan T, Maytin EV. Vitamin D3 enhances the apoptotic response of epithelial tumors to aminolevulinate-based photodynamic therapy. Cancer Res. 2011; 71(18): 6040-50.
Mack JA, Feldman RJ, Itano N, Kimata K, Lauer M, Hascall VC, Maytin EV. Enhanced Inflammation and Accelerated Wound Closure Following Tetraphorbol Ester Application or Full-Thickness Wounding in Mice Lacking Hyaluronan Synthases Has1 and Has3. J Invest Dermatol. 2011 Aug 18 [Epub ahead of print].
Warren CB, Lohser S, Wene LC, Pogue BW, Bailin PL, Maytin EV. Noninvasive fluorescence dosimetry to define protoporphyrin IX production rates in actinic keratoses following short-contact application of 5-aminolaevulinate. J Biomedical Optics 2010; 15(2) Sept/October, Issue 051607, pages 1-8.
Mack JA, Maytin EV. Persistent Inflammation and Angiogenesis during Wound Healing in K14-Directed Hoxb13 Transgenic Mice. J Invest Dermatol 2010; 130:856-65.
Lerner Research Institute
Mail Code NB21
9500 Euclid Avenue
Cleveland, Ohio 44195