Susan D. Reynolds, Assistant Professor
Ph.D. 1992 University of Rochester
Email: sdr1@pitt.edu
Research Interests:
Research in Dr. Reynolds' laboratory is centered on understanding mechanisms regulating regeneration, repair and remodeling of the tracheobronchial epithelium. Our basic science initiatives are relevant to understanding the pathogenesis of chronic lung diseases and serve as the basis for translational projects focused on development of therapeutic interventions involving cell-based therapy. Lung conditions that we hope to address include traditional airway diseases such as asthma, cystic fibrosis, and chronic bronchitis as well as those that are thought to impact the distal lung and involve the airways indirectly (bronchopulmonary dysplasia, chronic obstructive pulmonary fibrosis, and interstitial pulmonary fibrosis).
Our research plan has three main focus points:
First, we are using genetically modified mouse models to understand regulation of cell fate specification within the tracheobronchial stem cell hierarchy. We have hypothesized that ¦Â-catenin is a central regulator of this process and studies to date indicate that roles for Wnt/¦Â-catenin signaling in the proximal compartment are distinct from those it plays in the distal epithelium. Research projects within this area include: 1) use of cell type specific lineage tagging strategies (Cre recombinase-mediated introduction of a genomic rearrangement) to determine the differentiation potential of reparative cells and to correlate this functional characteristic with cell cycle frequency; 2) use of cell type specific Cre-mediated recombination to modify the ¦Â-catenin locus and assess necessity and sufficiency of ¦Â-catenin in regulation of cell proliferation and differentiation; and generation of novel transgenic mouse models to identify the signaling pathway upstream of ¦Â-catenin (ie. Wnt signaling).
Second, we are using a novel method to separate label-retaining (stem-like cells) and label diluting cells (stem cell progeny) of the tracheobronchial epithelium by flow cytometry. The sorted populations will be used to identify a set of cell surface markers that are unique to stem and transit amplifying cells and to purify specific cell types for in vitro analysis of signaling pathways. Since the tracheobronchial epithelium is maintained by a dual lineage hierarchy, these studies will use methods for analysis of both the basal and secretory cell lineages. The capacity to independently assess stem and transit amplifying cells is a distinguishing feature of studies focused on the proximal compartment and comparative studies of these two lineages is critical to understanding cell fate determination in this part of the airway.
Finally, we are developing methods for use of airway stem and progenitor cells in reconstruction of the lung. These studies being done in collaboration with members of the McGowen Institute for Regenerative Medicine and constitute a melding of their expertise in use of basement membrane as a scaffold for reconstruction of various structures and our knowledge of epithelial injury and repair. Our role in the current initiative is to shift these studies to a genetically tractable species such as mice. This will allow us to take advantage of transgenic models to purify various cell populations and to determine their function in the context of host injury and inflammation.
Recent Publications
Reynolds, S.D., Giangreco, A., Power, J.H.T., and Stripp, B.R., Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. (2000) Am. J. Path. 156:269.
Peake, J.L., Reynolds, S.D., Stripp, B.R., Stephens, K.E., and Pinkerton, K.E. Alteration of pulmonary neuroendocrine cells during epithelial repair of naphthalene-induced airway injury. (2000) Am. J. Path. 156:279.
Reynolds, S.D., Hong, K.U., Giangreco, A., Mango, G.W., Guron, C., Morimoto, Y., and Stripp, B.R. Conditional Clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. (2000) Am. J. Physiol. 278:L1256.
Zhao, B. Chua, S.S., Burcin, M.M., Reynolds, S.D., Stripp, B.R., Edwards, R.A., Finegold, M.J., Tsai, S.Y., and DeMayo, F.J. Phenotypic Consequences of Lung-specific Inducible Expression of FGF-3. (2001) Proc. Nat. Acad. Sci. 98:5898.
Hong, K.U.*, Reynolds, S.D.*, Giangreco, A., Hurley, C. and Stripp, B.R. CCSP-expressing Cells of the Airway Neuroepithelial body Microenvironment Include a Label Retaining Subset and are Critical for Epithelial Renewal Following Progenitor Cell Depletion. (2001) Am. J. Cell Respir. Cell Mol. Biol. 24:671-681 * authors contributed equally.
Giangreco A. Reynolds SD. Stripp BR. Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am J Path 16:173-82, 2002
Reynolds, S.D., Reynolds, P.R., Pryhuber, G.S., Finder, J.D., Stripp, B.R. Secretoglobins SCGB3A1 and SCGB3A2 define secretory cell subsets in mouse and human airways. (2002) Am. J. Resp. Crit. Care Med. 166:1498-1509.
Hong, K.U., Reynolds, S.D., Watkins S., Fuchs, E., Stripp, B.R. Basal cells are a multipotent progenitor cell capable of regenerating the bronchial epithelium. (2004) Am J Pathol. 164:577.
Giangreco, A., Shen, H., Reynolds, S.D., Stripp, B.R. Molecular phenotype of airway side population cells. Am J Physiol-Lung Cell Mol Physiol 2004 286:L624 (10.1152/ajplung.00149.2003).
Hong, K.U., Reynolds, S.D., Watkins S., Fuchs, E., Stripp, B.R. In vivo differentiation potential of tracheal cytokeratin 14-expressing cells: Evidence for subpopulations with multipotent and unipotent differentiation potential. Am J Physiol-Lung Cell Mol Physiol 286:L643 2004, (10.1152/ajplung.00155.2003).
Evans CM, Williams OW, Tuvim MJ, Nigam R, Mixides GP, Blackburn MR, DeMayo FJ, Burns AR, Smith C, Reynolds SD, Stripp BR, Dickey BF: Mucin Is Produced by Clara Cells in the Proximal Airways of Antigen Challenged Mice. Am J Respir Cell Mol Biol 2004, 31:382
Reynolds SD, Giangreco A, Hong KU, McGrath KE, Ortiz LA, Stripp BR, Airway injury in the pathophysiology of lung disease: Selective depletion of airway stem and progenitor cells potentates inflammation and alveolar dysfunction. American Journal of Physiology - Lung Cellular & Molecular Physiology. 2004, 287:L1256.
Reynolds, S.D*., Shen, H., Reynolds., PR., Betsuyaku, T., Pilewski, PM., Gambelli, F., DeGusippi, M., Ortiz, LA., B.R. Stripp. Molecular and Functional Properties of Lung Side Population Cells. *Corresponding author Am J Physiol Lung Cell Mol Physiol. 2007 Jan 12; [Epub ahead of print] PMID: 17142352
Everett, EE., Reynolds, SD., Pryhuber, GS., Yalowich, T., Stripp, BR., Altered progenitor cell utilization and epithelial remodeling in airways of neonates with BPD. Submitted
Reynolds SD, Teisanu, R, Zemke, A, Brockway, BL, Burton, C, Drake, JC, Giangreco, A, Stripp BR. ¦Âcatenin regulation of the bronchiolar stem and transit amplifying pools. Submitted
