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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 PublicationsKoch 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. Laskin. D.L.. Fakhrzadeh. L.. Heck. D.E.. Gerecke. D.. and Laskin. J.D. (2002). Upregulation of Phosphoinositide 3 Kinase and Protein Kinase B in Alveolar Macrophages Following Ozone Inhalation. Role of NF kB and STAT 1 in Ozone induced nitric oxide production and toxicity. Molecular and Cellular Biochemistry 234-235:91-98. Meirowitz NB. Smulian JC. Hahn RA. Zhou P. Shen-Schwarz S. Lambert GH. Gerecke DR. Gordon MK. (2002) Collagen messenger RNA expression in the human amniochorion in premature rupture of membranes. American Journal of Obstetrics & Gynecology. 187(6):1679-85. Gardner CR. Laskin JD. Dambach DM. Sacco M. Durham SK. Bruno MK. Cohen SD. Gordon MK. Gerecke DR. Zhou P. Laskin DL. (2002) Reduced hepatotoxicity of acetaminophen in mice lacking inducible nitric oxide synthase: potential role of tumor necrosis factor-alpha and interleukin-10. Toxicology & Applied Pharmacology. 184(1):27-36. Meirowitz NB. Smulian JC. Hahn RA. Zhou P. Shen-Schwarz S. Lambert GH. Gerecke DR. Gordon MK.(2002) Collagen messenger RNA expression in the human amniochorion in premature rupture of membranes. merican Journal of Obstetrics & Gynecology. 187(6):1679-85. Koch M. Foley JE. Hahn R. Zhou P. Burgeson RE. Gerecke DR. Gordon MK. (2001) alpha 1(Xx) collagen. a new member of the collagen subfamily. fibril-associated collagens with interrupted triple helices. Journal of Biological Chemistry. 276(25):23120-6. |
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