Involution is the process of extensive remodeling of the mammary gland that occurs during weaning. This process involves growth factors, hormones, structural proteins, and several proteases including matrix metalloproteases and plasminogen activators. We are primarily interested in defining the role of serine proteases during this phase of mammary development. To this end, we have been using variants of the serine protease inhibitor, Ecotin to specifically inhibit target proteases. I have demonstrated through in vivo studies that serine proteases are important in mammary remodeling and have identified a novel plasminogen activator involved in this process. This research is relevant to broadening our understanding of the role of proteases in tssue remodeling and will be used to develop a model of normal and pathological development of the mammary gland. We are using the resources available through the Computer Graphics Laboratory to search biological databases for sequence information and alignment. Modeling programs are used to study enzyme- inhibitor interactions and to develop new and potent protease inhibitors. These resources will be of further use in the characterization of novel proteases involved in mammary remodeling.
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