University of Cincinnati Department of Pediatrics

John M. Shannon, PhD

Title

Professor

Appointment

Professor of Pediatrics

Email

john.shannon@cchmc.org

Phone

513-636-2938

Fax

513-636-7868

Credentials

PhD University of California, Berkeley, 1979.

Awards and Honors

Franklin D. Roosevelt Grant from the March of Dimes

Research

The major area of research in my lab is the elucidation of the molecular mechanisms that regulate morphogenesis and differentiation of the lung epithelium. Normal lung development requires the coordinated expression of a number of genes in the correct place and at the proper time. Deviations from the normal lung developmental program can have debilitating or fatal results.

We have used methods of embryonic tissue separation and recombination to demonstrate that the eventual differentiated phenotype of the epithelium throughout the respiratory tract is dependent on diffusible inductive signals received from the mesenchyme with which it is associated. Lung mesenchyme induces tracheal epithelium to form lung, and tracheal mesenchyme induces lung epithelium to form trachea. A primary focus of the lab is to identify molecules that are differentially expressed in embryonic lung mesenchyme vs tracheal mesenchyme to identify molecules involved in specification of the distal lung phenotype. cDNA microarray techniques have generated a number of candidate genes for analysis, some of which are previously undescribed in the lung. Microarray analysis has also been used to identify genes that are expressed in the distal, but not proximal, respiratory epithelium.

One group of potential mediators of tissue interactions in the developing lung is the fibroblast growth factor (FGF) family of growth factors. A number of FGFs have been shown to be importantly involved in both lung morphogenesis and differentiation. One focus of my research is to define the individual and interactive role(s) played by the six FGF family members known to be expressed in the lung. Using microdissected embryonic lung and tracheal epithelia, we have shown that some FGFs are necessary, but not sufficient by themselves, to induce lung epithelial differentiation. Research is now focused on determining how FGFs affect expression of other molecular regulators known to be important for lung development. To this end we are using the techniques of RNA amplification and cDNA microarray analysis to identify genes specifically regulated by FGF family members during the earliest period of lung induction.

During normal lung development, both epithelial and mesenchymal cells interact with components of the extracellular matrix (ECM). We have previously demonstrated that one component of the ECM, chondroitin sulfate proteoglycans (CSPGs), are necessary for normal lung morphogenesis in vitro. We are now using transgenic mouse models to determine how specifically disrupting CSPGs in the lung affects normal development. In a related study we are investigating how disruption of Hedgehog signaling in the lung affects expression of CSPGs, as well as other genes.

Publications, Most Recent

John Shannon's publications as listed by PubMed.

Fujita, M., J.M. Shannon, C.G. Irvin, K.A. Fagan, C. Cool, A. Augustin, and R.J. Mason. 2001. Overexpression of tumor necrosis factor- alpha produces an increase in lung volumes and pulmonary hypertension.Am. J. Physiol. 280: L39-L49.

Shannon, J.M., T. Pan, L.D. Nielsen, K.E. Edeen, and R.J. Mason. 2001. Lung fibroblasts improve differentiation of rat type II cells in primary culture. Am. J. Respir. Cell Mol. Biol. 24: 235-244.

White, C.W., K.E. Greene, C.B. Allen, L.D. Nielsen, and J.M. Shannon. 2001. Elevated expression of surfactant proteins in newborn rats during development of tolerance to hyperoxic lung injury.Am. J. Respir. Cell Mol Biol. 25: 51-59.

Pan, T., R.J. Mason, J.J. Westcott, K. McCormick-Shannon, and J.M. Shannon. 2001. Rat alveolar type II cells inhibit lung fibroblast proliferation in vitro. Am. J. Respir. Cell Mol. Biol. 25: 353-361.

Shannon, J.M. and B.A. Hyatt. 2001. Tissue interactions in lung organogenesis. In: Basic Mechanisms of Pediatric Respiratory Disease, 2nd Edition. G.G. Haddad, S.H. Abman, and V. Chernick, eds. B.C. Decker Inc.

Greenberg, J.M., F.Y. Thompson, S.K. Brooks, J.M. Shannon, K.M. Shannon, J. E. Cameron, B.P. Mallory, and A.L Akeson. 2002. Mesenchymal expression of VEGF-D and VEGF-A defines vascular patterning in developing lung.Dev. Dyn. 224: 144-153.

Rice, W.R., J.J. Conkright, C. Na, M. Ikegami, J.M. Shannon, and T.E. Weaver. 2002. Maintenance of murine type II cell phenotype in vitro.Am. J. Physiol. 283: L256-L264.

Power, J.H.T., J.M. Shannon, P.C. Blumbergs, and W. Gei. 2002. Non-selenium glutathione peroxidase in human brain: elevated levels in Parkinson's disease and dementia with lewy bodies.Am. J. Pathol. 161: 885-894.

Hyatt, B.A., X. Shangguan, and J.M. Shannon. 2002. BMP4 modulates FGF-mediated induction of proximal and distal lung epithelial differentiation in mouse embryonic tracheal mesenchyme-free culture.Dev. Dyn. 225: 153-165.

Fujita, M., R.J. Mason, C. Cool, J.M. Shannon, N. Hara, and K.A. Fagan. 2002. Pulmonary hypertension in TNF-alpha overexpressing mice is associated with decreased VEGF gene expression.J. Appl. Physiol. 93: 2162-2170.

Fujita, M., J.M. Shannon, O. Morikawa, J. Gauldie, N. Hara, and R.J. Mason. 2003. Overexpression of tumor necrosis factor- diminishes pulmonary fibrosis induced by bleomycin or transforming growth factor-β. Am. J. Respir. Cell Mol. Biol. 29: 669-676.

Shannon, J.M., K.M. Shannon, M.S. Burhans, X. Shangguan, K. Srivastava, and B.A. Hyatt. 2003. Chondroitin sulfate proteoglycans are required for lung growth and morphogenesis in vitro.Am J. Physiol. 285: L1323-L1336.

McCormack, F.X. and J.M. Shannon. 2003. Role of the alveolar epithelium in the pathogenesis of pulmonary fibrosis. In: Interstitial Lung Disease. M.I. Schwarz and T.E. King Jr, eds. BC Decker, Inc. pp. 221-244.

Kubo, A., K. Shinozaki, J.M. Shannon, V. Kouskoff, M. Kennedy, S. Woo, H.J. Fehling, and G. Keller. 2004. Development of definitive endoderm from embryonic stem cells in culture.Development In Press.

Shannon, J.M. and B.A. Hyatt 2004. Epithelial-mesenchymal interactions in the developing lung.Ann. Rev. Physiol. In Press.

Professional Organization Memberships

American Thoracic Society

Special Interests

Lung morphogenesis and differentiation; isolation and characterization of genes differentially expressed in the developing lung; maintenance of alveolar lung cell differentiation; pulmonary vascular development; congenital diaphragmatic hernia

Presentations, MOst Recent:

Invited Speaker, Symposium on "Stem Cells and Stem Cell Therapy in the Developing and Adult Lung." American Thoracic Society International Conference, Seattle, WA. May, 2003.

Invited Speaker, Symposium on "Animal Models of Human Cardiopulmonary Development." Pediatric Academic Societies Meeting, Seattle, WA. May, 2003.

Invited Speaker, Federation of European Biochemical Society cell culture course. Dublin City University, Dublin, Ireland. September, 2002.

Invited Speaker, FASEB Summer Research Conference on "Lung Surfactant: Cellular and Molecular Biology. Saxtons River, VT. July, 2002.

Invited Speaker, FASEB Symposium on "Mesenchymal-Epithelial Interactions in Lung Development and Repair-Are Modeling and Remodeling One and the Same Process?" New Orleans, LA. April, 2002.

Tissue Interactions in Lung Development." Visiting Professor Lecture for 2001, Tissue Engineering Centre, Imperial College of London, London, England. July, 2001.

Grants

USPHS SCOR: "Pathobiology of lung development," Project 2, " Fibroblast growth factors in lung morphogenesis." Principal Investigator. 12/01/01-11/30/06.

USPHS SCOR: "Pathobiology of lung development," Core B, "Morphology." Co-Investigator. 12/01/01-11/30/06.

USPHS R01: "Chondroitin sulfate proteoglycans in lung development." John M. Shannon, Principal Investigator. 12/1/02- 11/30/06.

March of Dimes Birth Defects Foundation, Franklin Delano Roosevelt Research Grant, "Isolation of differentially expressed genes from embryonic lung mesenchyme." John M. Shannon, Principal Investigator. 1/1/03-12/31/04.