The research in my lab mostly involves using molecular biology techniques to study the expression of extracellular matrix genes. This is a natural extension of my graduate and post-doctoral experiences where I participated in the cloning of various collagen and laminin cDNAs and genes. Presently, the main focus of my laboratory is how matrix gene products may impart organs and tissues with known physical properties. One project examines these genes in fibrosis, a common result of chemical or toxicological insult. During fibrosis, the extracellular matrix is disorganized and in disarray resulting in a diseased state. This is especially true for the major matrix protein, collagen I fibrils. My hypothesis, which is supported by several publications and preliminary data, is that, collagens XII and XIV, sit on the surface of the collagen I fibrils and help regulate their size and organization. If the normal expression of these genes is disrupted, the collagen I fibrils that form will be abnormal and a pathology, such as fibrosis, will occur. My laboratory studies the collagen XII/XIV/I interaction not only in lung fibrosis, but in liver fibrosis, and pulmonary hypertension as well. My lab will continue using these three models to better understand the mechanism underlying excessive collagen deposition and fibril thickening with the ultimate goal being the development of more effective strategies to treat fibrotic or hypertensive tissues. One objective this year is to use the three models on transgenic mice that under-express collagen XII. We will determine if the pathologies in collagen XII-deficient mice are exacerbated in the various models. Future studies also include using paraquat or inhaled particulates as lung fibrosis inducers.

Another major research area in my lab involves developing models to test the efficacy of anti-vesicant agents for protection of skin damage after mustard gas exposure. In short the studies involve exposing mouse skin to mustard gas and using markers of skin damage (matrix metalloproteinases and skin laminins) to assess the extent of damage. Anti-vesicant skin protecting compounds are applied to mouse skin prior to mustard gas exposure and the same markers examined and compared to controls in a quantitative attempt to measure efficacy of protection. These studies will be continued and expanded to try and find additional markers of skin damage. In addition an in vitro mouse keratinocyte cell culture model is being examined as an alternative method (using the same markers of induced damage) to reduce the numbers of live animals required for experiments.

	Tzortzaki, E.G., Tischfield, J.A., Sahota, A., Siafakas, N.M., Gordon, M.K., and Gerecke, D.R. Expression of FACIT collagens XII and XIV during bleomycin-induced pulmonary fibrosis in mice. Anatom. Rec. 275:1073-1080, 2003
	Koch, M., Laub,F., Zhou, P., Hahn, R.A., Tanaka, S., Burgeson, R.E., Gerecke, D.R. , Ramirez, F. and Gordon, M.K., Collagen XXIV, a vertebrate fibrillar collagen with structural features of invertebrate collagen: selective expression in developing cornea and bone. J. Biol. Chem.278:43236-43244, 2003
	Gerecke, D.R. , Huang, X., Liu, B., and Birk, D.E., Complete primary structure and genomic organization of the mouse COL14A1 gene. Matrix Biology, 22:209-216, 2003