Name: Douglas Coffin
Office: SB 271
Doug Coffin, Ph.D., was hired as an Associate Professor for Molecular Genetics in the Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy. Doug came to Missoula from the McLaughlin Research Institute in Great Falls where he was a Research Scientist for five years. He is a graduate of SUNY College at Buffalo (B.A., M.A., 1985) and the SUNY HSC at Syracuse (Ph.D., 1989). After receiving his Ph.D., Doug worked as a post-doctoral fellow at the University of Washington and the University of Cincinnati before coming to Montana.
Most major pathologies include a problem with angiogenesis as a component or secondary complication. Angiogenesis, a.k.a. "neovascularization" for new growth of blood vessels is involved in cancer, heart disease, diabetes, and birth defects. There are a variety of molecules that regulate angiogenesis including growth factors, hormones, and metabolites. In most cases, research attempts to fundamentally understand these regulatory processes with the ultimate goal of either inhibiting or facilitating angiogenesis, depending on the pathology. For example, in cancer the goal is to inhibit angiogenesis, depriving a malignant tumor the means to obtain nutrients and dispose of nitrogenous wastes. In heart disease the goal is to facilitate angiogenesis, enhancing growth of collateral coronary arteries as the established vessels close from atherosclerosis.
The Coffin lab focuses on the structure and function of angiogenic growth factor genes, particularly the FGFs, in cardiovascular disease and other pathologies. Their approach uses transgenesis and gene targeting to create murine models and test gene function. They have succeeded in making transgenic and knockout mice for FGF-2, and mice with modifications in other cell cycle/cell proliferation genes that model tumor angiogenesis, coronary angiogenesis and human dwarfisms. Overall they have over 500 mice and more than 10 different lines of transgenic or knockout mice for their experiments.
Xiao, L., Naganawa, T., Lorenzo, J., Carpenter, T.O., Coffin, J.D. and Hurley, M.M. (2010). Nuclear isoforms of fibroblast growth factor 2 are novel inducers of hypophosphatemia via modulation of FGF23 and KLOTHO. J Biol Chem 285:2834-2846.
Liao, S., Bodmer, J.R., Azhar, M., Newman, G., Coffin, J.D., Doetschman, T. and Schultz, J.E. (2010). The influence of FGF2 high molecular weight (HMW) isoforms in the development of cardiac ischemia-reperfusion injury. J Mol Cell Cardiol
Xiao L., Liu P., Li X., Doetschman T., Coffin J.D., Drissi H., Hurley M.M. Exported 18-kDa isoform of fibroblast growth factor-2 is a critical determinant of bone mass in mice. J Biol Chem. 2009 Jan 30;284(5):3170-82. Epub 2008 Dec 4.
Sabbieti M.G., Agas D., Xiao L., Marchetti L., Coffin J.D., Doetschman T., Hurley M.M. (2009) Endogenous FGF-2 is critically important in PTH anabolic effects on bone. J Cell Physiol. 2009 Apr;219(1):143-51.
Zucchini S., Buzzi A., Barbieri M., Rodi D., Paradiso B., Binaschi A., Coffin J.D., Marzola A., Cifelli P., Belluzzi O., Simonato M. (2008) FGF-2 overexpression increases excitability and seizure susceptibility but decreases seizure-induced cell loss. J. Neuroscience 2008 Dec 3;28(49):13112-24.
Naganawa T., Xiao L., Coffin J.D., Doetschman T., Sabbieti M.G., Agas D., and Hurley M.M. (2008). Reduced expression and function of bone morphogenetic protein-2 in bones of Fgf2 null mice. J Cell Biochem. 103(6): 1975-88
Bunderson M., Pereira F., Schneider M.C., Shaw P.K., Coffin J.D., and Beall H.D. (2006). Manganese enhances peroxynitrite and leukotriene E4 formation in bovine aortic endothelial cells exposed to arsenic. Cardiovasc Toxicol 6:15-23.
Grass T.M., Lurie D.I., and Coffin J.D. (2006). Transitional angiogenesis and vascular remodeling during coronary angiogenesis in response to myocardial infarction. Acta Histochem 108:293-302.
Hurley M.M., Okada Y., Xiao L., Tanaka Y., Ito M., Okimoto N., Nakamura T., Rosen C.J., Doetschman T., and Coffin J.D. (2006). Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice. Biochem Biophys Res Commun 341:989-994.
Marie P.J., Coffin J.D., and Hurley M.M. (2005). FGF and FGFR signaling in chondrodysplasias and craniosynostosis. J Cell Biochem 96:888-896.
Sobue T., Naganawa T., Xiao L., Okada Y., Tanaka Y., Ito M., Okimoto N., Nakamura T., Coffin J.D., and Hurley M.M. (2005). Over-expression of fibroblast growth factor-2 causes defective bone mineralization and osteopenia in transgenic mice. J Cell Biochem 95:83-94.
Bunderson M., Brooks D.M., Walker D.L., Rosenfeld M.E., Coffin J.D., and Beall H.D. (2004). Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesis. Toxicol Appl Pharmacol 201:32-39.
Xiao L., Naganawa T., Obugunde E., Gronowicz G., Ornitz D.M., Coffin J.D., and Hurley M.M. (2004). Stat1 controls postnatal bone formation by regulating fibroblast growth factor signaling in osteoblasts. J Biol Chem 279:27743-27752.
Ismail J.A., Poppa V., Kemper L.E., Scatena M., Giachelli C.M., Coffin J.D., and Murry C.E. (2003). Immunohistologic labeling of murine endothelium. Cardiovasc Pathol 12:82-90.
Okada Y., Montero A., Zhang X., Sobue T., Lorenzo J., Doetschman T., Coffin J.D., and Hurley M.M. (2003). Impaired osteoclast formation in bone marrow cultures of Fgf2 null mice in response to parathyroid hormone. J Biol Chem 278:21258-21266.
Xiao L., Liu P., Sobue T., Lichtler A., Coffin J.D., and Hurley M.M. (2003). Effect of overexpressing fibroblast growth factor 2 protein isoforms in osteoblastic ROS 17/2.8 cells. J Cell Biochem 89:1291-1301.
Bunderson M., Coffin J.D., and Beall H.D. (2002). Arsenic induces peroxynitrite generation and cyclooxygenase-2 protein expression in aortic endothelial cells: possible role in atherosclerosis. Toxicol Appl Pharmacol 184:11-18.
Sahni M., Raz R., Coffin J.D., Levy D., and Basilico C. (2001). STAT1 mediates the increased apoptosis and reduced chondrocyte proliferation in mice overexpressing FGF2. Development 128:2119-2129.
Wishcamper C.A., Coffin J.D., and Lurie D.I. (2001). Lack of the protein tyrosine phosphatase SHP-1 results in decreased numbers of glia within the motheaten (me/me) mouse brain. J Comp Neurol 441:118-133.
Brewster J.L., Martin S.L., Toms J., Goss D., Wang K., Zachrone K., Davis A., Carlson G., Hood L., and Coffin J.D. (2000). Deletion of Dad1 in mice induces an apoptosis-associated embryonic death. Genesis 26:271-278.