Find a Health Care Professional / Researcher

John M. Shannon, PhD

Title

Professor, Division of Pulmonary Biology

Appointment

Professor of Pediatrics, University of Cincinnati College of Medicine

Email

john.shannon@cchmc.org

Phone

513-636-2938

Fax

513-636-7868

Credentials

AB: Biology, University of California, Santa Cruz, 1972.

PhD: University of California, Berkeley, 1979.

Position History

9/72 - 6/76 USPHS Predoctoral Trainee, Department of Zoology, University of California Berkeley, CA.
1/77 - 3/77 Teaching Assistant, Course: Advanced Lab in Cell Biology, Department of Zoology, University of California Berkeley, CA.
4/77 - 6/77 Teaching Assistant, Course: General Zoology
Department of Zoology, University of California Berkeley, CA.
6/76 - 6/79 USPHS National Research Service Award, Department of Zoology, University of California Berkeley, CA.
9/79 - 8/82 USPHS Postdoctoral Fellow, Department of Anatomy, University of Colorado, Health Sciences Center
Denver, CO.
9/82 - 84 Instructor, Department of Medicine, University of Colorado, Health Sciences Center, Denver, CO.
9/84 - 7/90 Assistant Professor, Department of Medicine, University of Colorado, Health Sciences Center, Denver, CO.
7/90- 7/98 Associate Professor, Department of Medicine, University of Colorado, Health Sciences Center, Denver, CO.
9/84 - 8/90 Assistant Faculty Member, Department of Medicine, National Jewish Medical and ResearhCenter,
Denver, CO.
8/90-7/98 Associate Faculty Member, Department of Medicine, National Jewish Medical and Research Center, Denver, CO.
2/98-7/99 Associate Professor, Department of Pathology, University of Colorado, Health Sciences Center, Denver, CO.
7/98-7/99 Professor, Department of Medicine, University of Colorado, Health Sciences Center, Denver, CO.
7/98-7/99 Senior Faculty Member, Department of Medicine, National Jewish Medical and Research Center, Denver, CO.
7/99-present Professor, Department of Pediatrics, Children’s Hospital Medical Center, Cincinnati, OH.
7/99-present Professor, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
1/00-present Faculty, Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Children’s Hospital Research Foundation,
Cincinnati, OH.

Awards and Honors

Franklin D. Roosevelt Fellow, March of Dimes, 1999-2003.
National Research Service Award Trainee (National Cancer Institute), 6/1976 - 1979.
United States Public Health Service Predoctoral Trainee, 9/1972 - 6/1976.
Honors in Biology, University of California, Santa Cruz, 6/1972.
General Honors, Cowell College, University of California, Santa Cruz, 6/1972.
Honors at Entrance, University of California, Santa Cruz, 9/1968.

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.

Research Grants and Contracts

USPHS R01: Alveolar type II cells in vitro: Effect of KGF. Robert J. Mason, Principal Investigator. Sub-contract to John M. Shannon. 4/1/06-3/31/11. $13,083 annual direct costs.
USPHS R01: Role of HIF-1 in fetal lung epithelial differentiation. John M. Shannon, Principal Investigator. 2/01/07- 1/31/12. $346,579 annual direct costs.

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.

Hyatt, B.A., X. Shangguan, and J.M. Shannon. 2004. FGF10 induces SP-C and BMP4 and regulates proximal-distal patterning during lung bud morphogenesis.Am. J. Physiol. 287: L1116-L1126.

Greenberg, J.M., F.Y. Thompson, S.K. Brooks, J.M. Shannon, and A. Akeson. 2004. Slit and robo expression in the developing mouse lung. Dev. Dyn. 230: 350-360.

Oblander, S., Z. Zhou, B. Starcher, J.M. Shannon, K. Tryggvason, and S.S. Apte. 2005. Membrane type 1 matrix metalloproteinase (MT1-MMP or MMP-14) is required for mouse lung and salivary gland development. Dev. Biol. 277: 255-269.

Fujita, M., J.M. Shannon, H. Ouchi, D.R. Voelker, Y. Nakanishi, and R.J. Mason. 2005. Serum surfactant protein D is decreased in acute and chronic inflammation in mice. Cytokine 31: 25-33.

Van Vranken, B., H.M. Romanska, J.M. Polak, H.J. Rippon, J.M. Shannon, and A.E. Bishop. 2005. Co-culture of embryonic stem cells with pulmonary mesenchyme: a microenvironment that promotes differentiation of pulmonary epithelium.Tissue Eng. 11: 1177-1187.

Arkovitz, M. S., B.A. Hyatt, and J.M. Shannon. 2005. Lung development is not necessary for diaphragm development in mice. J. Pediatr. Surg. 40: 1390-1394.

Portnoy, J., T. Pan, C.A. Dinarello, J.M. Shannon, J.Y Westcott, L. Zhang, and R.J. Mason. 2006. Alveolar
type II cells inhibit fibroblast proliferation: role of IL-1. Am. J. Physiol. 290: L307-316.

Lin, S., A.K. Perl, and J.M. Shannon. 2006. Erm/Thyroid transcription factor 1 interactions modulate transcription of surfactant protein. C. J. Biol. Chem. 281: 16716-16726.

Asikainen, T.M., L.Y. Chang, D.C. McCurnin, J.J. Coalson, B.K. Schneider, N.S. Waleh, M. Ikegami, J.M. Shannon, V.T. Winter, P. Grubb, R.I. Clyman, B.A. Yoder, J.D. Crapo, V. Gunzler, and C.W. White. 2006. Improved lung development and function through stimulation of hypoxia-inducible factor in the primate model of bronchopulmonary dysplasia in vivo. FASEB J. 20: 1698-1708.

Chen, X., B.A. Hyatt, M.L. Mucenski, R.J. Mason, and J.M. Shannon. 2006. Identification and characterization of a lysophosphatidylcholine acyltransferase in alveolar type II cells. Proc. Natl. Acad. Sci. 103: 11724-11729.

Metzger, D.E., Y. Xu, and J.M. Shannon. 2007. Elf5 is an epithelium-specific, fibroblast growth factor-sensitive transcription factor in the embryonic lung. Dev. Dyn. 236: 1175-1192.

Lin, S., Y. Xu, A. Bosserhoff, A.M. Malkinson, and J.M. Shannon. 2008. Misexpression of MIA disrupts lung
morphogenesis and causes neonatal death. Dev. Biol. 316: 441-455.

Metzger, D.E., M.T. Stahlman, and J.M. Shannon. 2008. Misexpression of Elf5 disrupts lung branching and
inhibits epithelial differentiation. Dev. Biol. 320: 149-160.

Ahmad, A., S. Ahmad, L. Glover, S. Miller, J.M.Shannon, X. Guo, J.P. Bridges, J.B. Schaack, S.P. Colgan, and C.W. White. 2009. Adenosine A2A receptor is a unique angiogenic target of HIF-2 in pulmonary endothelial cells.Proc. Nat. Acad. Sci. In press.

Bridges, J.P., M. Ikegami, L.L. Brilli, X. Chen, R.J. Mason, and J.M. Shannon. 2009. LPCAT1 regulates phospholipid synthesis and is required for the transition to air breathing. J. Clin. Invest. In revision.

Shannon, J.M. and Greenberg, J.M. 2009. Lung growth and development. In: Textbook of Respiratory Medicine, 5. J. Murray, J. Nadel, C. Broaddus, T. Martin, T. King, D. Schraufnagel, and R.J. Mason, eds. Elsevier.

Presentations, Most Recent

Invited Speaker, National Jewish Health Center. Identification and Characterization of LPCAT1, an Acyltransferase Critical for Alveolar Lipid Homeostasis. 03/2009.
Invited Speaker, British Thoracic Society, Winter Meeting. Characterization of LPCAT1, an Enzyme Critical for Alveolar Lipid Homeostasis. London, England. 12/2008.
Invited Speaker, Department of Biochemistry, University of Western Ontario. LPCAT: A novel lung glycerolipid acyltransferase critical for surfactant homeostasis. London, Ontario, Canada. 01/2008.
Invited Speaker, FASEB Summer Research Conference on Lung Surfactant: Cellular and Molecular Biology. Saxtons River, VT. 07/2004.
Invited Speaker, Symposium on Stem Cells and Stem Cell Therapy in the Developing and Adult Lung. American Thoracic Society International Conference, Seattle, WA. 05/2003.
Invited Speaker, Symposium on Animal Models of Human Cardiopulmonary Development. Pediatric Academic Societies Meeting, Seattle, WA. 05/2003.
Endoderm Section Leader and Lecturer, Graduate Course in Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH. 05/2003.

Professional Organization Memberships

Abstracts

Pan, T., J.M. Shannon, J.Y. Westcott, and R.J. Mason. 2000. Rat alveolar type II cells inhibit fibroblast proliferation by secreting IL-1 that in turn stimulates the production of PGE2 by fibroblasts. Am. J. Respir. Crit. Care Med. 161: A161.

Fehrenbach, H., M. Kasper, T. Pan, J.M. Shannon, D. Schuh, M. Muller, and R.J. Mason. 2000. Changes in the expression pattern of pro-apototic Bax may trigger the switch from hyperplasia to apoptosis in rat alveolar type II cells after KGF treatment in vivo. Am. J. Respir. Crit. Care Med. 161: A162.

Fujita, M., J.M. Shannon, O. Morikawa, K. Kuwano, N. Hara, and R.J. Mason. 2001. Overexpression of TNF-alpha in the lungs protects against pulmonary fibrosis induced by bleomycin or TGF-beta.Am. J. Respir. Crit. Care Med. 163: A42.

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. Crit. Care Med. 163: A742.

Perl, A-K., S. Wert, B. Hyatt, J.M. Shannon, M.A. Impagnatiello, G. Christofori, and J.A. Whitsett. 2001. Sprouty-4 inhibits pulmonary branching morphogenesis but not cellular differentiation in vivo.Am. J. Respir. Crit. Care Med. 163: A761.

Shannon, J.M., K. McCormick-Shannon, X.F. Shangguan, M.S. Burhans, and B.A. Hyatt. 2002. Sulfated proteoglycans are required for lung growth and differentiation in vitro. Am. J. Respir. Crit. Care Med. 165: A224.

Hyatt, B.A. and J.M. Shannon. 2002. The roles for FGFs, BMP4, and Shh in transdifferentiation of mouse tracheal epithelium in mesenchyme-free culture. Am. J. Respir. Crit. Care Med. 165: A641.

Hyatt, B.A., X. Shangguan, and J.M. Shannon. 2003. FGF10 induces SP-C expression in cultured embryonic mouse tracheal epithelium. Am. J. Respir. Crit. Care Med. 167: A43.

Lin, S. and J.M. Shannon. 2003. Erm regulates SP-C expression in the presence of TTF-1. Am. J. Respir. Crit. Care Med. 167: A285.

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

Funded Training Programs

Neonatology Training Program

Advisory Committees

6/2001 Advisory group, Veterans Administration Medical Center of Cincinnati Research Enhancement Award
Program.

Conference Administration

8/2006 Co-Organizer, FASEB Summer Research Conference on Lung Surfactant: Cellular and Molecular Biology.
8/2008 Organizer, FASEB Summer Research Conference on Lung Epithelium in Development and Disease.