The research in my group is focused on photochemistry in a variety of ways and is currently directed in the two programs described below.
Cellular Responses to Localized Oxidative Stress
As part of an NIH program project grant with Kathy Held (Radiation Oncology, MGH), Howard Liber (Colorado State) and Kevin Prise (Gray Cancer Institute, UK) we are studying cellular responses to oxidative stress, initiated at different sub-cellular locations by different reactive oxygen species generated by photosensitization. In particular, we compare the nature and magnitude of macromolecular damage (DNA, lipids, proteins) and the resultant cellular response mechanisms (repair, signaling, toxicity etc) that occur as a function of time after the oxidative insult. We are most interested in unraveling the sequence of events that lead to diffusion of modifications within and between cells. For example, the mechanism and temporal features of the generation of DNA lesions from initial lipid peroxidation reactions. We also study longer-term consequences to cells that experience an oxidative insult, including an adaptive response, where the cell becomes more resistant to oxidative stress a few hours after a non-lethal dose of ROS, and bystander effects, where cells that were not directly subjected to stress show similar responses to the treated cells over a longer period where the mechanism and temporal response of cell-cell communication is our goal. We make specific use of a time-lapse fluorescence microscopy system to study these responses in real time, allowing a more over-arching view of oxidative stress at the cellular level to be determined.
Photoactivated Tissue Repair
In close collaboration with Dr. Kochevar at Wellman we have been working in recent years on the development of novel photochemical approaches to wound closure in a variety of different tissues. Photochemical Tissue Bonding (PTB) involves application of a photosensitizing dye to the tissue surfaces followed by visible light illumination to initiate crosslinking of the tissue and formation of a strong, water-tight seal. No foreign body is involved so the process does not aggravate inflammation or scarring in the tissue. It is a viable alternative to mechanical methods such as sutures for wound closure in tissues where sutures are difficult to place or lead to deleterious side effects e.g., in the eye. In addition, the water-tight seal is particularly appropriate for tubular tissues like nerves and blood vessels where leakage would be particularly problematic. We hold intellectual property around this technology and have recently expanded our research from tissue bonding to synthesis and placement of bioengineered materials using photochemical means. Pre-clinical studies have been carried out in vivo in the repair of blood vessel, nerve, tendon, vocal fold, cornea and skin and a human trial is commencing for closure of skin excisions following skin cancer removal using PTB to reduce scarring and improve cosmetic appearance. PTB is a platform technology and we are looking into many more applications as the research continues.