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Philip Sannes, PhD

Professor, Cell Biology

Office: 919.515.7656

Alumni Distinguished Undergraduate Professor
Ph.D.: The Ohio State University
Post-doctoral Training: Medical University of South Carolina, Division of Pathobiology
Biological Barriers
Research has mainly been focused on the mechanisms which regulate repair and renewal of epithelial surfaces in the pulmonary alveolus. This has included how extracellular matrix (ECM), especially their sulfated components, influence cellular responses to growth factors and alter specific gene expression leading to proliferation and ending with differentiation or transition. Recent studies have examined specific signaling pathways that intersect and control cell fate decisions in adult lung. These processes are understood to be key in determining whether epithelial injury effectively resolves, or results in irreversible fibrosis. Influenced by results obtained through a recent RO3 mechanism focused on a cohort of idiopathic pulmonary fibrosis (IPF) patients obtained from the Lung Tissue Research Consortium and the NIH, we continue to expand on our historical interests in normal alveolar epithelial turnover to more translational application of specific biologic principals to lung pathology, and specifically fibrosis. These include specific cell-cell and cell-ECM interactions as they control the initiation and perpetuation of fibrogenesis in lung diseases like IPF.


Our work has focused on the mechanisms that influence the activities of a key cell in the adult pulmonary alveolus - the type II (AT2) epithelial cell – that plays a crucial role in repair processes following injury. In addition to producing surfactant, it acts as a facultative stem cell with the capacity to renew itself as well as serve as the precursor for AT1 cells, which cover over 90% of the alveolar surface area. We’ve developed data suggesting that the interaction of alveolar epithelial cells with specific components of the extracellular matrix (ECM) directly affects their ability to proliferate, to synthesize effector molecules vital to the repair process (such as cytokines and additional ECM components), and to effectively differentiate into type I (AT1) cells.

AT1 Images

We’ve shown that microdomains within the alveolar basement membrane (ABM) associated with the AT2 cells are low in sulfate content (black “dots” in figure at right, and double arrows), which promotes their biologic responsiveness to critical growth factor signals (such as fibroblast growth factors -1 and -2) and normal proliferation - a major component of the repair process. The adjacent ABM microdomains of AT1 cells are high in sulfate content (“black dots”; single arrows), which reduces the cell’s biologic responsiveness by slowing or impeding proliferation leading either to normal or, in some cases, aberrant repair.
Recent studies using discovery-based gene expression profile analysis were undertaken on freshly isolated human AT2 (hAT2) cells grown on extracellular matrix (ECM) substrata known to either support (type I collagen) or retard (Matrigel) the early transdifferentiation process into hAT1-like cells. Cell type-specific expression patterns analyzed by Illumina Human HT-12 BeadChip yielded over 300 genes that were up- or down-regulated. Candidate genes significantly induced or down-regulated during hAT2 transition to hAT1-like cells compared to non-transitioning hAT2 cells were identified. Major functional groups were also recognized, including those of signaling and cytoskeletal proteins as well as genes of unknown function. Expression of established signatures of hAT2 and hAT1 cells, such as surfactant proteins, caveolin-1, and channels and transporters, was confirmed (see figure below). Selected novel genes further validated by qRT-PCR, protein expression analysis, and/or cellular localization included SPOCK2, PLEKHO1, SPRED1, RAB11FIP1, PTRF/CAVIN-1 and RAP1GAP. These results further demonstrate the utility of genome-wide analysis to identify relevant, novel cell type-specific signatures of early ECM-regulated alveolar epithelial transdifferentiation processes in vitro.

Philip Sannes Cell research

Figure description: Paraffin-embedded normal human lung tissue sections were deparaffinized and immunofluorescence was performed for PTRF/CAVIN-1 (red) and caveolin-1 (green, left panel) or SP-C (green, right panel); DAPI (nuclei, blue). Caveolin and PTRF co-localize while PTRF and SP-C do not.
But these interconnected events can be influenced or interrupted by protracted injury or genetic variants, which result in activation of alternative or default pathways. This can involve shifts in epithelial phenotype which enable their breaching of the barrier of the basal lamina and invasion of the subepithelial interstitum. The result is fibroblast-like cell expansion and scar formation, as seen in many fibrogenic diseases of the lung. The factors that control this alternative pathway are poorly understood, and recent studies have demonstrated that they involve at least some of the known fibrogenic factors such as TGFb, FGF9, Wnt5A and Wnt7B. But the specific signaling events involved likely precede and go beyond those already known, and involve combinations ligands, signaling sequences, and target genes. Current studies focus on these poorly understood mechanisms.

  • Expression of WNT5A in Idiopathic Pulmonary Fibrosis and Its Control by TGF-β and WNT7B in Human Lung FibroblastsNewman, D.R., Sills, W.S., Hanrahan, K., Ziegler, A., Tidd, K.M., Cook, E., Sannes, P.L. | J Histochem Cytochem 2016. 64(2) 99–111.
  • Heparin inhibits LPS-induced COX-2 Expression in H292 CellsYi, N. Y., Newman, D.R., Morales Johansson, H, Zhang, H., and P.L. Sannes | Experimental Lung Research 2015 Nov;41(9):499-513.
  • (2014) MARCKS-dependent mucin clearance and lipid metabolism in ependymal cells is required for maintenance of forebrain homeostasis during agingMuthusamy, N., L. Sommerville, A. Moeser, D. Stumpo, P. Sannes, K. Adler, P. Blackshear, J. Weimer, H.T. Ghashghaei | Aging Cell Oct; 14(5):764-73.
  • Whole-Genome Analysis of Temporal Gene Expression during Early Transdifferentiation of Human Lung Alveolar Epithelial Type 2 Cells In VitroJohansson H.M., D.R. Newman, and P.L. Sannes | PLoS ONE 2014; 9(4): e93413.
  • Expression of Fibroblast Growth Factor-9 in Normal Human Lung and Idiopathic Pulmonary FibrosisCoffey, E, D.R. Newman, P.L. Sannes | J. Histochem. Cytochem. 2013; 61(9):671-679. *Featured on cover, J. Histochem. Cytochem September, 2013*
  • Over-expression of Human Endosulfatase-1 Exacerbates Cadmium-induced Injury to Transformed Human Lung Cells In VitroZhang, H., D. R. Newman, J. C. Bonner, P. L. Sannes | Tox. & Appl. Pharm. 2012 Nov 15;265(1):27-42.
  • Wnt7B in fibroblastic foci of idiopathic pulmonary fibrosisMeuten, T, A. Hickey, K. Franklin, B. Grossi, J. Tobias, H. Zhang, D.R. Newman, S. Jennings, M. Correa, P. L. Sannes | Resp. Res. 2012; 28;13(1):62.
  • HSulf-1 Inhibits ERK and AKT Signaling and Decreases Cell Viability in vitro in Human Lung Epithelial CellsZhang, H., D. R. Newman, P. L. Sannes | Respir Res. 2012. 13(1):69.
  • Heterotaxin: A TGF-β Signaling Inhibitor Identified in a Multi-Phenotype Profiling Screen in Xenopus EmbryosDush, M.K., A.L. McIver, M.A. Parr, D.D. Young, J. Fisher, D.R. Newman, P.L. Sannes, M.L. Hauck, A. Deiters, N. Nascone-Yoder | Chem.Biol. 2011.18:252-263.