Stephen P. Sugrue, Ph.D.

Professor and Sr Assoc Dean of Research Affairs
Anatomy and Cell Biology
email: sugrue@ufl.edu
phone: (352) 273-8475
fax: (352) 273-5232


Research Interests - References - Biosketch

Research Interests

The long-term goal of my research is to discover the molecular determinants of the regulation of cell-cell adhesion in epithelium. Substantial data now support the notion that loss/modification of cell-cell adhesion is a key step in progression to the loss of the epithelial barrier. Studies underway in my lab are directed toward understanding the specifics a nuclear and cell adhesion-related protein, pinin (Pnn), that we discovered and now propose functions as a regulator of cell-cell adhesion and the epithelial phenotype. Recent data pertaining to Pnn has taken us in a significantly new and exciting direction toward the exploration of the involvement of Pnn in the linkage of transcriptional repression and mRNA processing. We wish to examine the mechanism by which Pnn affects downstream gene expression pertaining to epithelial adhesion through its specific association with transcriptional repressors via its binding to the co-repressor, CtBP. To reconcile the seemingly disparate nuclear roles of Pnn, we have conducted proteomic characterization of the specific nuclear complex(es) that contain Pnn. Finally, we have examined the consequences of the loss of Pnn expression in the corneal epithelium by generation of conditional Pnn-knock-out and Pnn-hypomorphic (knock-down) mice. The data derived from these studies will provide important new information pertaining to epithelial adhesion and will contribute towards our ability to modify the adhesive capacity of epithelial cells, thus bringing us closer to reversing the phenotypes of adhesion related diseases of the corneal epithelium.

Three projects, currently underway, are directed to the study of Pnn at three different levels of organization. First we study of the role of Pnn in the regulation of the E-cadherin promoter. We next study Pnn in the context of higher order structures of sub-nuclear organization. Finally we explore Pnn in the framework of the corneal epithelial cell and the structures of the anterior segment. The goal of this work is to be parfocal, i.e., to accomplish the change in magnification, while remaining focused on the goal of understanding how Pnn affects corneal epithelial adhesion and maintenance of the epithelial barrier.

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References

  1. Shi Y, Ouyang P, Sugrue SP. Characterization of the gene encoding Pinin/DRS/memA and evidence for its potential tumor suppressor function. Oncogene, 2000; 19:289-297.  Pubmed
  2. Shi Y, Tabesh M, Sugrue SP. Role of Cell Adhesion-Associated Protein, Pinin, (DRS/memA), In Corneal Epithelial Migration. IOVS, May 2000, Vol. 41, No. 6, pg. 1337-1345.  Pubmed
  3. Shi, J., Sugrue SP. Dissection of protein linkage between keratins and pinin, a protein with dual location at desmosome-intermediate filament complex and in the nucleus. J Biol Chem, 2000. May 19; 275(20):14910-5.  Pubmed
  4. Shi Y, Simmons M, Seki T, Oh P, and Sugrue SP. Change in gene expression subsequent to induction of Pinin/DRS/memA: increase in p21cip1/waf1. Oncogene, 2001. 20:4007-4018.  Pubmed
  5. Zimowska G, Shi J, Simmons M, Shi Y, and Sugrue SP. Pinin/DRS/memA interacts with SRp75, SRm300 and SRrp130 in corneal epithelial cells. IOVS, November 2003. 44(11):4715-4723.  Pubmed
  6. Alpatov R, Munguba GC, Caton P, Joo JH, Shi Y, Shi Y, Hunt ME, and Sugrue SP. Nuclear Speckle-Associated Protein Pnn/DRS Binds to the Transcriptional Corepressor CtBP and Relieves CtBP-Mediated Repression of the E-Cadherin Gene. Mol Cell Biol, Dec. 2004. 10223-10235.  Pubmed
  7. Joo JH, Alpatov R, Munguba GC, Jackson MR, Hunt ME, and Sugrue, SP. Reduction of Pnn by RNAi induces loss of cell-cell adhesion between human corneal epithelial cells. Mol Vis, Feb. 18 2005. 11:133-42.  Pubmed

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Biosketch
    Education
    1975B.Sc., Providence College (Biology), Providence, Rhode Island
    1979Ph.D., University of Cincinnati College of Medicine (Anatomy), Cincinnati, Ohio
     
    Postdoctoral Training
    1979-1981Research Associate in Anatomy and Cellular Biology, Harvard Medical School
    1981-1983Research Fellow in Oral Biology, Harvard Medical School
     
    Academic Appointments
    1983-1989Assistant Professor of Anatomy and Cellular Biology, Harvard Medical School
    1989-1993Associate Professor of Anatomy and Cellular Biology, Harvard Medical School
    1993-1995Associate Professor, Cell Biology, Harvard Medical School
    1995-1996Associate Professor of Anatomy and Cell Biology University of Florida College of Medicine
    1996-2000Chairman and Associate Professor, Department of Anatomy and Cell Biology University of Florida College of Medicine
    2000-PresentChairman and Professor, Department of Anatomy and Cell Biology University of Florida College of Medicine

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