Professor of Molecular Genetics
Doug Coffin, Ph.D., is a full Professor of Molecular Genetics in the Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences. Doug comes to Missoula from the McLaughlin Research Institute in Great Falls where he was a Research Scientist for the last 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. He has served in the Montana legislature (2013 session) as a Representative For HD 93, covering the university distrcit and surrounding areas.
Physiology, Pharmacology, Developmental Biology, Toxicology, Cardiology, Pharmacogenetics, Genetics.
Personal Statement for Research
Douglas Coffin, Ph.D. is a Professor of Molecular Genetics in the Department of Biomedical & Pharmaceutical Sciences, Skaggs School of Pharmacy, at The University of Montana. I joined UM in 1998 after serving as a Scientist at the McLaughlin Research Institute for five years. My research has focused on developmental biology and molecular/developmental genetics: First studying the origins and mechanisms of blood vessel development in avian embryos (chick & quail) and then mammalian cardiovascular, nervous and skeletal system development. We produced the first FGF2 transgenic and null mice and used them to study growth factor regulation of morphogenesis, producing mouse models for human diseases and disorders such as osteoporosis, dwarfism and seizure disorders. My publication record shows expertise in developmental morphogenesis particularly regarding embryonic stem cell differentiation into various lineages during development. There is a strong emphasis on collaborative work both producing and utilizing transgenic and gene targeted mice for FGF2 regulation of morphogenesis. I was on sabbatical for spring 2012, at the University of Washington and the University of Connecticut Health Sciences Center. I was on unpaid leave during the spring 2013 semester, serving as a Representative (HD 93, Missoula) in the Montana legislature. I did, however, continue to teach my on-line Pharmacogenetics course (Phar 430) while serving in the legislature. As a result of my sabbatical and after my leave, my research has taken a new direction, collaboratively working on a project with Dr. Diana Lurie (Dept. BMED, U. Montana) on natural product research. Our project with Laila Pharmaceutical (Chennai, India) focused on use of an Alzheimer’s disease transgenic mouse model (5XFAD) to test the efficacy of novel curcumin compounds to mitigate the amyloidosis and neuroinflammation that propagate neurodegeneration in AD.
Novel Applications of Natural Products for Alzheimer’s Disease Research and Therapeutics
Function of FGF2 pleiotropisms in skeletal development
Stem Cell Therapeuticcs and Dynamics in Mammalian Development
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.
1. Coffin JD, McGarry MP, Isseroff H. Proline induced hemolytic anemia in fascioliasis. Proc Soc Exp Biol Med. 1984;177(1):92-96. http://www.ncbi.nlm.nih.gov/pubmed.
2. Coffin JD, Poole TJ. Embryonic vascular development: Immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos. Development. 1988;102(4):735-748. http://www.ncbi.nlm.nih.gov/pubmed.
3. Coffin JD, Harrison J, Schwartz S, Heimark R. Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo. Dev Biol. 1991;148(1):51-62. http://www.ncbi.nlm.nih.gov/pubmed.
4. Coffin JD, Florkiewicz RZ, Neumann J, et al. Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. Mol Biol Cell. 1995;6(12):1861-1873. http://www.ncbi.nlm.nih.gov/pubmed.
5. Zhou M, Sutliff RL, Paul RJ, et al. Fibroblast growth factor 2 control of vascular tone. Nat Med. 1998;4(2):201-207. http://www.ncbi.nlm.nih.gov/pubmed.
6. Zucchini S, Buzzi A, Barbieri M, et al. Fgf-2 overexpression increases excitability and seizure susceptibility but decreases seizure-induced cell loss. J Neurosci. 2008;28(49):13112-13124. http://www.ncbi.nlm.nih.gov/pubmed?term=Coffin%2C%20J%20Douglas%5BAuthor%5D. doi: 10.1523/JNEUROSCI.1472-08.2008.
7. Vaccarino FM, Schwartz ML, Raballo R, et al. Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat Neurosci. 1999;2(3):246-253. http://www.ncbi.nlm.nih.gov/pubmed. doi: 10.1038/6350.
8. Carlson GA, Borchelt DR, Dake A, et al. Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Hum Mol Genet. 1997;6(11):1951-1959. http://www.ncbi.nlm.nih.gov/pubmed.
9. Kuzis K, Coffin JD, Eckenstein FP. Time course and age dependence of motor neuron death following facial nerve crush injury: Role of fibroblast growth factor. Exp Neurol. 1999;157(1):77-87. http://www.ncbi.nlm.nih.gov/pubmed. doi: 10.1006/exnr.1999.7014.
10. Wishcamper CA, Coffin JD, Lurie DI. Lack of the protein tyrosine phosphatase SHP-1 results in decreased numbers of glia within the motheaten (me/me) mouse brain. J Comp Neurol. 2001;441(2):118-133. http://www.ncbi.nlm.nih.gov/pubmed.
11. Lurie DI and Coffin, JD (2015) The role of bacopa monnieri in inflammatory and neurodegenerative diseases. In Occurrences, Structure, Biosynthesis, and Health Benefits Based on Their Evidences of Medicinal Phytochemicals in Vegetables and Fruits. Ed. Noboru Motohashi. Volume 3. Nova Science Publishers, NY, USA, Chapter 2, pg 27-61.
Publications (Coffin JD and Coffin DJ)
1. Coffin, J.D., McGarry, M.P. and Isseroff, H. (1984). Proline induced hemolytic anemia in fascioliasis. Proc Soc Exp Biol Med 177:92-96.
2. Coffin, J.D. and Poole, T.J. (1988). Embryonic vascular development: immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos. Development 102:735-748.
3. Poole, T.J. and Coffin, J.D. (1988). Developmental angiogenesis: quail embryonic vasculature. Scanning Microsc 2:443-448.
4. Poole, T.J. and Coffin, J.D. (1989). Vasculogenesis and angiogenesis: two distinct morphogenetic mechanisms establish embryonic vascular pattern. J Exp Zool 251:224-231.
5. Coffin, J.D., Harrison, J., Schwartz, S. and Heimark, R. (1991). Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo. Dev Biol 148:51-62.
6. Coffin, J.D. and Poole, T.J. (1991). Endothelial cell origin and migration in embryonic heart and cranial blood vessel development. Anat Rec 231:383-395.
7. Doetschman, T., Shull, M., Kier, A. and Coffin, J.D. (1993). Embryonic stem cell model systems for vascular morphogenesis and cardiac disorders. Hypertension 22:618-629.
8. Coffin, J.D., Florkiewicz, R.Z., Neumann, J., Mort-Hopkins, T., Dorn, G.W., 2nd, Lightfoot, P., German, R., Howles, P.N., Kier, A., O'Toole, B.A. and et al. (1995). Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice. Mol Biol Cell 6:1861-1873.
9. Carlson, G.A., Borchelt, D.R., Dake, A., Turner, S., Danielson, V., Coffin, J.D., Eckman, C., Meiners, J., Nilsen, S.P., Younkin, S.G. and Hsiao, K.K. (1997). Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Hum Mol Genet 6:1951-1959.
10. Davis, M.G., Zhou, M., Ali, S., Coffin, J.D., Doetschman, T. and Dorn, G.W., 2nd (1997). Intracrine and autocrine effects of basic fibroblast growth factor in vascular smooth muscle cells. J Mol Cell Cardiol 29:1061-1072.
11. Lightfoot, P.S., Swisher, R., Coffin, J.D., Doetschman, T.C. and German, R.Z. (1997). Ontogenetic limb bone scaling in basic fibroblast growth factor (FGF-2) transgenic mice. Growth Dev Aging 61:127-139.
12. Naski, M.C., Colvin, J.S., Coffin, J.D. and Ornitz, D.M. (1998). Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development 125:4977-4988.
13. Zhou, M., Sutliff, R.L., Paul, R.J., Lorenz, J.N., Hoying, J.B., Haudenschild, C.C., Yin, M., Coffin, J.D., Kong, L., Kranias, E.G., Luo, W., Boivin, G.P., Duffy, J.J., Pawlowski, S.A. and Doetschman, T. (1998). Fibroblast growth factor 2 control of vascular tone. Nat Med 4:201-207.
14. Fulgham, D.L., Widhalm, S.R., Martin, S. and Coffin, J.D. (1999). FGF-2 dependent angiogenesis is a latent phenotype in basic fibroblast growth factor transgenic mice. Endothelium 6:185-195.
15. Kuzis, K., Coffin, J.D. and Eckenstein, F.P. (1999). Time course and age dependence of motor neuron death following facial nerve crush injury: role of fibroblast growth factor. Exp Neurol 157:77-87.
16. Vaccarino, F.M., Schwartz, M.L., Raballo, R., Nilsen, J., Rhee, J., Zhou, M., Doetschman, T., Coffin, J.D., Wyland, J.J. and Hung, Y.T. (1999). Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat Neurosci 2:848.
17. Vaccarino, F.M., Schwartz, M.L., Raballo, R., Nilsen, J., Rhee, J., Zhou, M., Doetschman, T., Coffin, J.D., Wyland, J.J. and Hung, Y.T. (1999). Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat Neurosci 2:246-253.
18. Zhadanov, A.B., Provance, D.W., Jr., Speer, C.A., Coffin, J.D., Goss, D., Blixt, J.A., Reichert, C.M. and Mercer, J.A. (1999). Absence of the tight junctional protein AF-6 disrupts epithelial cell-cell junctions and cell polarity during mouse development. Curr Biol 9:880-888.
19. 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.
20. Chiotti, K., Choo, S.J., Martin, S.L., Reichert, C., Grass, T.M., Duran, C.M. and Coffin, J.D. (2000). Activation of myocardial angiogenesis and upregulation of fibroblast growth factor-2 in transmyocardial-revascularization-treated mice. Coron Artery Dis 11:537-544.
21. Montero, A., Okada, Y., Tomita, M., Ito, M., Tsurukami, H., Nakamura, T., Doetschman, T., Coffin, J.D. and Hurley, M.M. (2000). Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J Clin Invest 105:1085-1093.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. He, W., Greenwell, R.J., Brooks, D.M., Calderon-Garciduenas, L., Beall, H.D. and Coffin, J.D. (2007). Arsenic exposure in pregnant mice disrupts placental vasculogenesis and causes spontaneous abortion. Toxicol Sci 99:244-253.
36. Pereira, F.E., Coffin, J.D. and Beall, H.D. (2007). Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite--Potential mechanism in the development of atherosclerosis. Toxicol Appl Pharmacol 220:164-177.
37. 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 103:1975-1988.
38. Zucchini, S., Buzzi, A., Barbieri, M., Rodi, D., Paradiso, B., Binaschi, A., Coffin, J.D., Marzola, A., Cifelli, P., Belluzzi, O. and Simonato, M. (2008). Fgf-2 overexpression increases excitability and seizure susceptibility but decreases seizure-induced cell loss. J Neurosci 28:13112-13124.
39. Sabbieti, M.G., Agas, D., Xiao, L., Marchetti, L., Coffin, J.D., Doetschman, T. and Hurley, M.M. (2009). Endogenous FGF-2 is critically important in PTH anabolic effects on bone. Journal of cellular physiology 219:143-151.
40. Xiao, L., Liu, P., Li, X., Doetschman, T., Coffin, J.D., Drissi, H. and Hurley, M.M. (2009). Exported 18-kDa isoform of fibroblast growth factor-2 is a critical determinant of bone mass in mice. J Biol Chem 284:3170-3182.
41. 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. 2010 Jun;48(6):1245-54.
42. 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.
43. Xiao, L., Sobue, T., Esliger, A., Kronenberg, MS., Coffin, JD., Doetschman. T., Hurley, MM. (2010). Disruption of the Fgf2 gene activates the adipogenic and suppresses the osteogenic program in mesenchymal marrow stromal stem cells. Bone 47(2):360-70.
44. Fei Y, Xiao L, Doetschman T, Coffin DJ, Hurley MM. Fibroblast growth factor 2 stimulation of osteoblast differentiation and bone formation is mediated by modulation of the Wnt signaling pathway. J Biol Chem. 2011 Nov 25;286(47):40575-83
45. Itkin T, Ludin A, Gradus B, Gur-Cohen S, Kalinkovich A, Schajnovitz A, Ovadya Y, Kollet O, Canaani J, Shezen E, Coffin DJ, Enikolopov GN, Berg T, Piacibello W, Hornstein E, Lapidot T. FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of stromal cells, c-Kit activation and CXCL12 downregulation. Blood. 2012 May 29.
46. Sabbieti MG, Agas D, Marchetti L, Coffin JD, Xiao L, Hurley MM. BMP-2 differentially modulates FGF-2 isoform effects in osteoblasts from newborn transgenic mice. Endocrinology. 2013 Aug;154(8):2723-33.