Gilbert Morris, PhD
Associate Professor of Pathology
Tulane Cancer Center Program Member
Address: 1430 Tulane Ave., Box SL-79, New Orleans, LA 70112-2699
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 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 30 papers relating to transcriptional regulation and control of cell growth. He has served on a NIH grant review panel and as a reviewer for numerous journals.
The Morris laboratory is interested in the molecular biology of lung injury and repair and the transcriptional regulation of the gene encoding proliferating cell nuclear antigen (PCNA). Specific interests are enumerated below.
- p53 expression and asbestos inhalation: Dr. Morris' laboratory has demonstrated the expression of the p53 tumor suppressor protein at sites of fibrotic lesions after inhalation exposure of rodents to asbestos. To characterize p53 function in asbestos-induced pulmonary fibrosis, Dr. Morris has been comparing cell proliferation and consequent pulmonary pathology of normal and p53-deficient mice after exposure to asbestos. In addition, transgenic mice have been prepared with diminished or augmented p53 expression in the lung epithelium. Analyses of fibrogenesis in these novel transgenic animals after inhalation exposure to asbestos fibers are underway. Preliminary analyses suggest that mice with compromised function of p53 in the lung epithelium display a reduced fibrogenic response to asbestos.
- p53 in lung cancer: A strong correlation exists between mutations in the p53 gene and malignant conversion. To assess the role of p53 in lung carcinogenesis, transgenic mice with lung-specific expression of a dominant negative form of p53 were developed. The mutant p53-expressing mice are expected to display 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 and to identify agents that contribute to neoplastic conversion in the lung.
- Regulation of PCNA expression in irradiated cells: The Morris laboratory has shown that the p53 tumor suppressor protein binds upstream of the PCNA promoter and regulates expression of a PCNA-CAT reporter construct in irradiated cells. Thus, a p53-mediated mechanism accounts for induction of PCNA for purposes of DNA repair. To evaluate this pathway in vivo, transgenic mice have been prepared with the human PCNA promoter fused to a CAT reporter. Interbreeding these PCNA-CAT transgenic mice with the animals with altered p53 expression in the lung will provide the means of evaluating this DNA damage inducible pathway in mouse lung epithelial cells exposed to genotoxic substances.
Shan B, Zhuo Y, Chin D, Morris CA, Morris GF, Lasky, JA. CDK9 is required for tumor necrosis factor-a stimulated MMP-9 expression in human lung adenocarcinoma cells. J Biol Chem 280, 1103-1111 (2005).
Shan B, Morris GF. Binding sequence-dependent regulation of the human proliferating cell nuclear antigen promoter by p53. Exp Cell Res (in press).
Morris GF, Notwick A, David O, Fermin C, Brody AR, Friedman M. Development of lung tumors in mutant p53-expressing mice after inhalation exposure to asbestos. Chest 125, Suppl. 5, 85S-86S (2004).
Zhuo Y, Hoyle GW, Zhang J, Morris GF, Lasky, JA. A novel murine PDGF-D splicing variant results in significant differences in peptide expression and function. Biochem Biophys Res Commun 308, 126-132 (2003).
Shan B, Xu J, Zhuo Y, Morris CA, Morris GF. Induction of p53-dependent activation of the human PCNA gene in chromatin by ionizing radiation. J Biol Chem 278, 44009-44017 (2003).
Ghosh S, Mendoza T, Ortiz LA, Hoyle GW, Fermin CD, Brody AR, Friedman M, Morris GF. Enhanced bleomycin sensitivity in mice expressing dominant negative p53 from the surfactant protein C promoter. Journal of Respiratory and Critical Care Medicine 166: 890-897 (2002)
Nelson A, Mendoza T, Hoyle GW, Brody AR, Fermin CD, Morris GF. Enhancement of fibrogenesis by the p53 tumor supressor protein in asbestos-exposed rodents. Chest 120: 33S-34S (2001
Kannabiran C, Morris GF and Mathews MB. Dual action of the adenovirus E1A 243R oncoprotein on the human proliferating cell nuclear antigen promoter: repression of transcriptional activation by p53. Oncogene 18, 7825-7833 (1999).
Xu J, Morris GF. p53-mediated regulation of proliferating cell nuclear antigen (PCNA) expression in cells exposed to ionizing radiation. Mol Cell Biol 19: 12-20 (1999).
Morris GF, Brody AR. Molecular mechanisms of particle-induced lung disease. pages 305-333. In: Environmental and Occupational Medicine. Rom WR Ed. Little, Brown and Company, Boston, MA. (1998).
Mishra A, Liu JY, Brody AR, Morris GF. Inhaled asbestos fibers induce p53 expression in the rat lung. Am J Resp Cell Mol Biol 16: 479-485 (1997).