Dr. Morris received his B.S. in Chemistry from the University of Georgia in 1975. He started graduate school in the Chemistry Department at Florida State University in 1976 where he studied small RNA synthesis during sea urchin development with Dr. W. F. Marzluff and obtained his Ph.D. in 1982. Post-doctoral training with Dr. Marzluff, was followed in 1985 by a brief post-doctoral position with Dr. E. S. Weinberg at the University of Pennsylvania studying histone biosynthesis during sea urchin development. In 1986, Dr. Morris received a post-doctoral fellowship from the Arthritis Foundation to work on autoimmunity with Dr. M. B. Mathews at Cold Spring Harbor Laboratory. Upon receiving a NIH post-doctoral fellowship later that year, Dr. Morris changed the focus of his project to regulation of proliferating cell nuclear antigen (PCNA), a DNA replication and repair protein. Dr. Morris maintained his interest in regulation of PCNA expression while he was promoted to Staff Associate in 1989 and Staff Investigator (Assistant Professor equivalent) in 1992 at Cold Spring Harbor Laboratory. He came to an Assistant Professor position in the Department of Pathology at Tulane University Health Sciences Center in 1993 and began work in lung biology. He reached the academic rank of Associate Professor in 1999. Dr. Morris has published over 40 papers relating to transcriptional regulation, control of cell growth and mechanisms of lung disease. He has served on grant review panels for the National Institutes of Health and the National Science Foundation and as a reviewer for numerous journals.
The Morris laboratory is interested in the molecular biology of lung injury and repair with a particular interest in fibrogenesis and carcinogenesis.
a. Modeling lung tumorigenesis in mice. Our laboratory has demonstrated expression of the p53 tumor suppressor protein at sites of fibrogenesis after inhalation exposure of rodents to asbestos. To characterize p53 function in this rodent model of asbestos-induced lung disease, we prepared transgenic mice that express a dominant negative mutant form of p53 from the surfactant protein C promoter (SPC-DNp53 mice). These animals with inhibited p53 function in the lung epithelium display enhanced fibrogenesis after exposure to bleomycin. A strong correlation exists between mutations in the p53 gene and malignant conversion. The phenotypic alterations of the SPC-DNp53 mice described above have disrupted p53 function in the epithelial cells of the small airways and the peripheral lung. This animal model is being used to study lung carcinogenesis induced by inhaled agents linked to human lung cancer, i.e. cigarette smoke and asbestos, to model the human disease in mice. Moreover, interbreeding SPC-DNp53 mice with mice harboring a mutant K-Ras allele (K-RasLA1) accelerates lung tumor progression.
b. Lung tumor promotion by IL-17. The overwhelming majority of human lung cancers are associated with exposure to cigarette smoke. Recent findings demonstrate that inhaled cigarette smoke elicits a T helper 17 (Th17) inflammatory phenotype. Interleukin-17 (IL-17), the hallmark cytokine of the Th17 inflammatory phenotype, displays pro- and anti-tumorigenic properties in a manner that varies according to tumor type and assay system. To investigate the role of IL-17 in lung tumor progression, we used an autochthonous tumor model (K-rasLA1 mice). IL-17 induced matrix metalloproteinase-9 (MMP-9) protein and mRNA expression in K-rasLA1 mice. In accord with this finding, IL-17 promoted increased MMP-9 expression in mutant K-Ras-expressing murine lung epithelial (mK-Ras-LE) cells in culture, which corresponded to increased cell motility and invasiveness. Our results indicate that IL-17 stimulates lung tumor progression, in part, via enhanced expression of MMP-9 that includes stabilization of the MMP-9 mRNA via altered function of a mRNA splicing factor.
c. Inflammasome repression by cigarette smoke. Inhaled asbestos activates the NLRP3 inflammasome in mice. Our data shows that cigarette smoke represses inflammasome activation. This finding suggests that tobacco smoke most likely impairs fiber clearance, in accordance with previous findings by others. We are exploring the relationship between the immunosuppressive effects of cigarette smoke and the development of lung disease in our murine models. Using inhaled asbestos as an inducer of lung disease allows us to examine mechanisms of fibrogenesis and carcinogenesis in an animal model that develops diseases identical to humans exposed to these 2 toxic substances.
Lin, Z., C. Nguyen, B. Xu, E.K. Flemington, G.F. Morris. IL-17A in the pathogenesis of lung adenocarcinoma. Annals of the American Thoracic Society (Supplement 2) S125 (2018).
Morris, G. F., S. Danchuk, Y. Wang, B. Xu, R. J. Rando, A. R. Brody, B. Shan and D. E. Sullivan. Cigarette smoke represses the innate immune response to asbestos. Physiol Rep 3(12), (2015).
Xu, B., Guenther, J.F., Pociask, D.A., Wang, Y., Kolls, J.K., You, Z., Shan, B., Sullivan, D.E., Morris, G.F. Promotion of lung tumor growth by interleukin-17. American Journal of Physiology, Lung Cellular and Molecular Physiology 307(6):L497-508 (2014).
C. Li, H.T. Nguyen, Y. Zhuang, Z. Lin, E.K. Flemington, S.P. Kantrow, G.F. Morris, D.E. Sullivan, B. Shan. Comparative profiling of miRNA expression of lung adenocarcinoma cells in two-dimensional and three-dimensional cultures. Gene 511, 143-150 (2012).
Li C, Nguyen HT, Zhuang Y, Lin Y, Flemington EK, Guo W, Guenther J, Burow ME, Morris GF, Sullivan D, Shan B. Post-transcriptional Up-regulation of miR-21 by Type I Collagen. Molecular Carcinogenesis. 50, 563-70 (2011).
J.F. Guenther, J.E. Cameron, H.T. Nguyen, D.E. Sullivan, B.Shan, J.A. Lasky, E.K. Flemington, G.F. Morris Modulation of lung inflammation by the Epstein-Barr virus protein Zta. American Journal of Physiology, Lung Cellular and Molecular Physiology 299(6) Dec:L771-84 (2010).
Shan, B. and Morris, G.F. Binding sequence-dependent regulation of the human proliferating cell nuclear antigen promoter by p53. Experimental Cell Research 305, 10-22 (2005).
Shan, B., Xu, J., Zhuo, Y., Morris, C.A. and Morris, G.F. Induction of p53-dependent activation of the human PCNA gene in chromatin by ionizing radiation. Journal of Biological Chemistry 278, 44009-44017 (2003).
Xu, J. and Morris, G.F. p53-mediated regulation of proliferating cell nuclear antigen (PCNA) expression in cells exposed to ionizing radiation. Molecular and Cellular Biology 19: 12-20 (1999).
Mishra, A., Liu, J.Y., Brody, A.R., and Morris, G.F. Inhaled asbestos fibers induce p53 expression in the rat lung. American Journal of Respiratory Cell and Molecular Biology 16: 479-485 (1997).
Morris, G.F., Bischoff, J.R., and Mathews, M.B. Transcriptional activation of the human proliferating cell nuclear antigen promoter by p53. Proceedings of the National Academy of Sciences 93: 895-899 (1996).
Morris, G.F., Labrie, C. and Mathews, M.B. Modulation of transcriptional activation of the proliferating cell nuclear antigen promoter by the adenovirus E1A 243-residue oncoprotein depends on proximal activators. Molecular and Cellular Biology 14: 543-553 (1994).
Morris, G.F. and Mathews, M.B. Regulation of proliferating cell nuclear antigen during the cell cycle. Journal of Biological Chemistry 264: 13856-13864 (1989).
Morris, G.F., Price, D.H. and Marzluff, W.F. Synthesis of U1 RNA in a DNA-dependent system from sea urchin embryos. Proceedings of the National Academy of Sciences USA 83: 3674-3678 (1986).
Xu, B., Guenther, J.F., Pociask, D.A., Wang, Y., Kolls, J.K., You, Z., Shan, B., Sullivan, D.E., Morris, G.F. Promotion of lung tumor growth by interleukin-17. American Journal of Physiology, Lung Cellular and Molecular Physiology 307(6):L497-508 (2014).
C. Li, H.T. Nguyen, Y. Zhuang, Z. Lin, E.K. Flemington, S.P. Kantrow, G.F. Morris, D.E. Sullivan, B. Shan. Comparative profiling of miRNA expression of lung adenocarcinoma cells in two-dimensional and three-dimensional cultures. Gene 511, 143-150 (2012).
Li C, Nguyen HT, Zhuang Y, Lin Y, Flemington EK, Guo W, Guenther J, Burow ME, Morris GF, Sullivan D, Shan B. Post-transcriptional Up-regulation of miR-21 by Type I Collagen. Molecular Carcinogenesis 50, 563-70 (2011).
J.F. Guenther, J.E. Cameron, H.T. Nguyen, D.E. Sullivan, B.Shan, J.A. Lasky, E.K. Flemington, G.F. Morris Modulation of lung inflammation by the Epstein-Barr virus protein Zta. American Journal of Physiology, Lung Cellular and Molecular Physiology 299(6) Dec:L771-84 (2010).
Shan, B. and Morris, G.F. Binding sequence-dependent regulation of the human proliferating cell nuclear antigen promoter by p53. Experimental Cell Research 305, 10-22 (2005).
Shan, B., Xu, J., Zhuo, Y., Morris, C.A. and Morris, G.F. Induction of p53-dependent activation of the human PCNA gene in chromatin by ionizing radiation. Journal of Biological Chemistry 278, 44009-44017 (2003).
Xu, J. and Morris, G.F. p53-mediated regulation of proliferating cell nuclear antigen (PCNA) expression in cells exposed to ionizing radiation. Molecular and Cellular Biology 19: 12-20 (1999).
Mishra, A., Liu, J.Y., Brody, A.R., and Morris, G.F. Inhaled asbestos fibers induce p53 expression in the rat lung. American Journal of Respiratory Cell and Molecular Biology 16: 479-485 (1997).
Morris, G.F., Bischoff, J.R., and Mathews, M.B. Transcriptional activation of the human proliferating cell nuclear antigen promoter by p53. Proceedings of the National Academy of Sciences 93: 895-899 (1996).
Morris, G.F., Labrie, C. and Mathews, M.B. Modulation of transcriptional activation of the proliferating cell nuclear antigen promoter by the adenovirus E1A 243-residue oncoprotein depends on proximal activators. Molecular and Cellular Biology 14: 543-553 (1994).
Morris, G.F. and Mathews, M.B. Regulation of proliferating cell nuclear antigen during the cell cycle. Journal of Biological Chemistry 264: 13856-13864 (1989).
Morris, G.F., Price, D.H. and Marzluff, W.F. Synthesis of U1 RNA in a DNA-dependent system from sea urchin embryos. Proceedings of the National Academy of Sciences USA 83: 3674-3678 (1986).
