We are at the end of the beginning in understanding MMP biology…

Metalloproteinases have equally or more important roles as efficient processing enzymes of many bioactive mediators such as cytokines, chemokines, growth factors, their receptors and specific matrix protein anchors for these molecules. Limited and specific processing of bioactive mediators can lead to profound alterations in cell behavior resulting in shedding of cell surface molecules, activation and inactivation of signaling molecules-sometimes converting activity from agonists to antagonists, and for certain proteins, exposing cryptic biologically active epitopes and neoproteins from precursor extracellular molecules of unrelated function. These diverse and important functions potentially explain the paradoxical positive and negative effects of MMPs in development, wound healing, learning, ageing and in diseases such cancer and macular degeneration. Hence, a dramatically increased understanding of the physiological functions of MMPs is clearly required in order to understand the roles of MMPs and TIMPs in pathology and to devise rational targeting strategies for therapeutic intervention with new generations of MMP inhibitors.

The 2005 MMP Gordon Research Conference will present the most recent and innovative research in MMPs, related proteinases and their inhibitors in a multidisciplinary manner and in a new program format. Moreover, many new and establishing investigators have been invited to present their work alongside those from established laboratories. Several short talks are reserved for trainees that will be selected from the poster abstracts and a few full speaker slots have been held for the latest breaking stories. Together with the recreational activities possible at Big Sky, we hope this ensures a vibrant, interactive, enthusiastic and fun meeting that features the most innovative metalloproteinase research of our time. We have brought in a number of investigators new to the MMP field, which is an indication of the vigor of the field.

In Montana 2005, the processing functions of MMPs will be emphasized with respect to interconnections of the MMP family with signaling networks that alter overall cell behavior; in this regard the critical roles of the ADAMs in a large variety of cell surface shedding events will also be presented. The future outlook and potential for MMPIs in therapy of cancer and neurodegenerative diseases will be discussed throughout the meeting in relation to new discoveries on the positive and negative roles of MMPs. There are also emerging roles of metalloproteinases in infection. The importance of MMPs in physiological turnover of collagen will be both challenged and supported; trafficking and localization of cell surface MMPs and a potential MMP inhibitor, RECK, will be discussed as a highly selective and cell controllable route to specificity and regulation of focal proteolysis. With many aspects of the biochemistry and molecular biology of MMPs now well established, it is time to turn to innovative methods of studying and resolving the dynamic nature of MMPs in catalysis and in vivo by new imaging techniques. The technical barrier to the proteomics of the substrate degradome is just beginning to establish roles of MMPs in physiological processes by system-wide level investigations remains in its infancy, but will be a topic of discussion.

It is hoped that these discussions and presentations will further nucleate the field to research the roles of metalloproteinases and their impact on in physiological processes at a system-wide level as an essential prerequisite to understanding their role in pathology.