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Collagen. lung. liver. heart. fibrosis. hypertensionCollagen I fibrils are responsible for the underlying basic architectural structure of almost every organ and tissue in vertebrates. In order to maintain the proper organ arrangement. these fibrils must be very specific sizes and in very specific arrangements in a particular tissue. Two of the modifiers to the sizes and arrangements of the collagen I fibrils are the collagens XII and XIV which coat the surface of the collagen I fibrils and extend outward away from them to interact with other molecules in the immediate vicinity. Thus. by changing the structure or amounts of collagens XII and XIV. collagen I fibrils can be greatly affected. The laboratory of Dr. Donald Gerecke is presently involved in the functional analysis of the extracellular matrix molecules. collagens XII and XIV as related to several medical problems. This is accomplished by a variety of biochemical and molecular biological techniques. The basic hypothesis is that these two molecules regulate the size and organization of collagen I fibrils. the main structural fibrils in all organs and tissues. If either of these collagens are disrupted then the collagen I fibrils in turn have an abnormal morphology which will result in tissue disorganization and ultimately a disease state. In order to examine the collagen I/XII/XIV interactions. Dr. Gerecke has three major projects in the laboratory. One project is looking at the functional roles of collagens in pulmonary fibrosis. a severely debilitating lung disease that is initiated as a result of many types of severe lung injury. Dr. Gerecke's laboratory is examining questions regarding the identity of mediators of the pathological process and the mechanisms involved in pulmonary structural remodeling. He does this through a mouse induced pulmonary fibrosis model. The second project is similar. examining the same problems in liver fibrosis. Liver fibrosis is caused by different factors than pulmonary fibrosis. such as chemical assault on the liver or alcoholism. This project involves carbon tetrachloride induced liver fibrosis in both mouse and rat models. The final project in the lab is involved with pulmonary hypertension. a complication of a variety of respiratory disorders whose common shared feature is hypoxia. or lack of oxygen to the tissue. During this process. the matrix is overproduced and its basic structure disrupted. leading to constriction of the arteries involved in shunting the blood from the heart to the lung so it can be oxygenated. The underlying mechanisms involving these detrimental changes is poorly understood and Dr. Gerecke is working to elucidate these processes with a hypoxia induced rat model. Selected PublicationsShakarjian MP, Heck DE, Gray JP, Sinko PJ, Gordon MK, Casillas RP, Heindel ND, Gerecke DR, Laskin DL, Laskin JD. (2009) Mechanisms mediating the vesicant actions of sulfur mustard after cutaneous exposure. Toxicol Sci. Oct 15. [Epub ahead of print] Chang YC, Sabourin CL, Lu SE, Sasaki T, Svoboda KK, Gordon MK, Riley DJ, Casillas RP, Gerecke DR. (2009) Upregulation of gamma-2 laminin-332 in the mouse ear vesicant wound model. J Biochem Mol Toxicol. 23(3):172-84. Gerecke DR, Chen M, Isukapalli SS, Gordon MK, Chang YC, Tong W, Androulakis IP, Georgopoulos PG. (2008) Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect. Toxicol Appl Pharmacol. 234(2):156-65. Koch M. Veit G. Stickler S. Bhatt P. Kutsch S. Zhou P. Reinders E. Hahn RA. Song R. Burgeson RE. Gerecke DR. Mundlos S. Gordon MK. (2006) Expression of type XXIII collagen mRNA and protein. J Biol Chem. 281(30):21546-57. Shakarjian MP. Bhatt P. Gordon MK. Chang YC. Casbohm SL. Rudge TL. Kiser RC. Sabourin CL. Casillas RP. Ohman-Strickland P. Riley DJ. Gerecke DR. (2006) Preferential expression of matrix metalloproteinase-9 in mouse skin after sulfur mustard exposure. J Appl Toxicol. 26(3):239-46. Tzortzaki EG. Koutsopoulos AV. Dambaki KI. Lambiri I. Plataki M. Gordon MK. Gerecke DR. Siafakas NM. (2006) Active remodeling in idiopathic interstitial pneumonias: evaluation of collagen types XII and XIV. J Histochem Cytochem. 54(6):693-700. Weinberger B. Hanna N. Laskin JD. Heck DE. Gardner CR. Gerecke DR. Laskin DL. (2005) Mechanisms mediating the biologic activity of synthetic proline. glycine. and hydroxyproline polypeptides in human neutrophils. Mediators Inflamm. 2005(1):31-8. Gerecke DR. Meng X. Liu B. Birk DE. (2004) Complete primary structure and genomic organization of the mouse Col14a1 gene. Matrix Biol. 22(7):595-601. Heck DE. Gerecke DR. Vetrano AM. Laskin JD. (2004) Solar ultraviolet radiation as a trigger of cell signal transduction. Toxicol Appl Pharmacol. 195(3):288-97. Gardner. C.R.. Laskin. J.D.. Dambach. D.M.. Chiu. H.. Durham. S.K.. Zhou. P.. Bruno. M.. Gerecke. D.R.. Gordon. M.K.. and Laskin. D.L. (2003). Exaggerated hepatotoxicity of acetominophen in mice lacking tumor necrosis factor Receptor-1: Potential role of inflammatory mediators. Tox. And Applied Pharm. 192(2):119-130. Tzortzaki. E.G.. Tischfield. J.A.. Sahota. A.. Gordon. M.K.. and Gerecke. D.R. (2003). Expression of FACIT collagens XII and XIV during Bleomycin-induced pulmonary fibrosis in mice. Anatomical Record 275:1073-1080. Koch. M.. Laub,F.. Zhou. P.. Hahn. R.A.. Tanaka. S.. Burgeson. R.E.. Gerecke. D.R.. Ramirez. F. and Gordon. M.K. (2003). 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. Gerecke. D.R.. Huang. X.. Liu. B.. and Birk. D.E. (2003). Complete primary structure and genomic organization of the mouse COL14A1 gene. Matrix Biology 22:209-216. |
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