Ocular Surface Development Laboratory

Ocular Surface Development and Gene Expression Laboratory
Principal Investigator: Shivalingappa (Shiva) Swamynathan

Mission Statement
• To understand gene regulation during ocular surface maturation and maintenance
• To identify novel therapeutic targets for diagnosis and treatment of ocular surface inflammatory disorders
• To train young scientists interested in ocular surface gene regulation

Ongoing Research in Ocular Surface Development and Gene Expression Laboratory
The ocular surface, consisting of the cornea, conjunctiva and the tear film, is critical for our vision. Ocular surface disorders account for bulk of the primary eye care services in the U.S, with dry eye alone affecting about 6 million women and 3 million men with moderate to severe symptoms and an additional 20 to 30 million people with mild symptoms. For us to be able to see clearly, we need a healthy and transparent cornea, which is somewhat analogous to your vehicle’s windshield. A strong and clean windshield is necessary to protect us from wind, dirt, rain, bugs, birds, pollen, falling leaves, rocks, etc, that will hurt if we are exposed. With usage, the windshield can get dirty and/or develop scratches, making it harder for us to see through. To keep the windshield clean, we use windshield washer liquid, and the windshield wipers. Similarly, health of the cornea (the windshield) depends on healthy conjunctiva and eyelids (windshield wipers) and a proper tear film (windshield washer liquid).

The Ocular Surface Development and Gene Expression Laboratory, led by Dr. Shivalingappa (Shiva) Swamynathan, an Assistant Professor in the Department of Ophthalmology, University of Pittsburgh School of Medicine, is interested in learning how the timely production of different proteins that make up our ocular surface is regulated during development and what goes wrong in ocular surface disorders. Recent research from the Swamynathan laboratory revealed the many critical contributions of Krüppel-like transcription factors Klf4 and Klf5 to maturation and maintenance of a healthy ocular surface. Ongoing research in the Swamynathan laboratory, supported by an RO1 grant award from the National Eye Institute is aimed at understanding the ocular surface expression and functions of Slurp1, a protein that is present in abundance in healthy ocular surface, and disappears during disease conditions. In a collaborative study with the Hendricks and Kinchington labs, the Swamynathan lab demonstrated that Slurp1 expression was significantly reduced in adenoviral keratitis model of corneal inflammation, restoration of which restricted corneal inflammation, suggesting an immunomodulatory role for Slurp1. Outcomes of ongoing studies in the Swamynathan laboratory are expected to reveal the value of Slurp1 as a novel diagnostic and/or therapeutic target for managing ocular surface inflammatory disorders.

Contact Information
Principal Investigator: Dr. Shivalingappa (Shiva) Swamynathan
Address:  203 Lothrop Street, Room 1025, Pittsburgh, PA 15213
Phone:    412-802-6437
Email:    Swamynathansk@upmc.edu

 

Selected Publications

Recent Publications
1. Gupta, D., Harvey, S.A., Kenchegowda, D., Swamynathan, S., and Swamynathan, S.K. * (2013). Regulation of mouse lens maturation and gene expression by Krüppel-like factor 4. Exp. Eye Res. 116: 205-218. PMID: 24076321
2. Swamynathan, S.K.* (2013). Ocular surface development and gene expression. J. Ophthalmol. 2013: 103947. doi: 10.1155/2013/103947. PMID: 23533700
3. Swamynathan, S., Buela, K.A, Kinchington, P., Misawa, H., Lathrop, K.L., Hendricks, R.L. and Swamynathan, S.K.* (2012). Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea. Invest. Ophthalmol. Vis. Sci. 53:8433-8446. PMID: 23139280
4. Kenchegowda, D., Harvey, S.A.K., Swamynathan, S., Lathrop, K.L. and Swamynathan, S.K.* (2012) Critical Role of Klf5 in Regulating Gene Expression during Post-Eyelid Opening Maturation of Mouse Corneas. PLoS ONE 7(9): e44771. doi:10.1371/journal.pone.0044771. PMID: 23024760
5. Kenchegowda, D, Swamynathan, S, Gupta, D, Wan, H, Whitsett, J, and Swamynathan S.K*. 2011. Conditional disruption of mouse Klf5 results in defective eyelids with malformed meibomian glands, abnormal cornea and loss of conjunctival goblet cells. Dev. Biol. 356:5-18. PMID: 21600198
6. Gupta, D., Harvey, S.A., Kaminski, N. and Swamynathan, S.K*. 2011. Mouse conjunctival forniceal gene expression during postnatal development and its regulation by Krüppel-like factor 4. Invest. Ophthalmol. Vis. Sci. 52:4951-4962. PMID: 21398290
7. Swamynathan, S., Kenchegowda, D., Piatigorsky, J. and Swamynathan, S.K*. 2011. Regulation of the corneal epithelial barrier function by Krüppel-like transcription factor 4. Invest. Ophthalmol. Vis. Sci. 52:1762-1769. PMID: 21051695
8. Swamynathan, S.K.* (2010). Krüppel-Like Factors: Three fingers in control. Human Genomics. 4(4): 1-8. PMID: 20511139
9. Young, R.D., Swamynathan, S.K.*, Boote, C., Mann, M., Quantock, A.J., Piatigorsky, J., Funderburgh, J.L., and Meek, K.M. 2009. Stromal edema in Klf4 conditional null mouse cornea is associated with altered collagen fibril organization and reduced proteoglycans. Invest. Ophthalmol. Vis. Sci. 50:4155-4161. PMID: 19387067
10. Swamynathan, S.K*., Davis, J. and Piatigorsky, J. (2008). Identification of candidate KLF4 target genes reveals the molecular basis of the diverse regulatory roles of KLF4 in the mouse cornea. Invest. Ophthalmol. Vis. Sci. 49: 3360-3370. PMID: 18469187
11. Kozmik, Z., Swamynathan, S.K., Ruzickova, J., Jonasova, K., Paces, C., Vlcek, C., and Piatigorsky, J. (2008). Cubozoan crystallins: Evidence for convergent evolution of Pax regulatory sequences. Evol. Dev. 10: 52-61. PMID: 18184357
12. Swamynathan, S.K. and Piatigorsky, J. (2007) Regulation of the mouse B-Crystallin and MKBP/HspB2 Promoter activities by shared and gene specific intergenic elements: The importance of context dependency. Int. J. Dev. Biol. 51: 689-700. PMID: 17939115
13. Swamynathan, S.K*., Katz, J.P., Kaestner, K.H., Ashery-Padan, R., Crawford, M.A. and Piatigorsky, J. (2007) Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells. Mol. Cell. Biol. 27: 182-194. PMID: 17060454
14. Kanungo, J., Swamynathan, S.K., and Piatigorsky, J. (2004) Abundant corneal gelsolin in Zebrafish and the ‘Four-Eyed’ fish, Anableps anableps: Possible analogy with multifunctional lens crystallins. Experimental Eye Res. 79: 949-956. PMID: 15642334
15. Swamynathan, S.K., Crawford, M.A., Robison Jr, W.G., Kanungo, J and Piatigorsky, J. (2003). Adaptive differences in the structure and macromolecular compositions of the air and water corneas of the four-eyed fish (Anableps anableps). FASEB Journal 17: 1996-2005. PMID: 14597669
16. Kanungo, J., Kozmik, Z, Swamynathan, S.K., and Piatigorsky, J. (2003) Gelsolin is a dorsalizing factor in zebrafish. Proc. Natl. Acad. Sci. USA. 100: 3287-3292. PMID: 12629212
17. Swamynathan, S.K. and Piatigorsky, J. (2002) Orientation-dependent influence of an intergenic enhancer on the regulation of transcription of the divergently transcribed mouse shsp/B-crystallin and MKBP/HSPB2 genes. J. Biol. Chem.  277: 49700-49706. PMID: 12403771

Book Chapters

1. Swamynathan, S.K. and Piatigorsky, J. (2008). Gene expression in cornea and lens. In Eye, Retina, and Visual System of the Mouse. Ed: Chalupa, L.M. and Williams, R. W. MIT Press.