Shivalingappa Swamynathan, PhD

Assistant Professor, Ophthalmology

Dr. Shivalingappa (Shiva) Swamynathan is an Assistant Professor in the Department of Ophthalmology, University of Pittsburgh School of Medicine, where he directs the Ocular Surface Development and Gene Expression Laboratory. Dr. Swamynathan received his doctoral degree from the Center for Cellular and Molecular Biology, Hyderabad, India. Dr. Swamynathan joined the Department of Ophthalmology in 2007, following post-doctoral training at the University of Missouri-Columbia, and NEI, NIH. Dr. Swamynathan is a member of the Association for Research in Vision and Ophthalmology (ARVO), Tear Film and Ocular Surface Society (TFOS) and International Society for Eye Research (ISER).
ACADEMIC POSITIONS
• Aug 2007-Present: Assistant Professor, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA
• Nov 2007-Present: Assistant Professor, Department of Cell Biology (secondary appointment), University of Pittsburgh School of Medicine, Pittsburgh, PA   
• Aug 2008-Present: Member Graduate Faculty, Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA
• Sep 2009-Present: Member faculty, McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA

Honors and Awards
1. Best Scientific Paper, 2009 Asia-ARVO Meeting    2009
2. National Eye Institute Career Development (K22) Award  2005-2011
3. Best Abstract Award, 2003 NEI Intramural Research Day, NIH.  2003
4. Senior Research Fellowship, University Grants Commission, India  1990 to 1995
5. Junior Research Fellowship, Indian Agricultural Research Institute  1988 to 1990
6. Indian National Merit Fellowship      1980 to 1987

Research Interests
Dr. Swamynathan is interested in understanding the regulation of gene expression during maturation and maintenance of ocular surface. In the mouse, following eye opening around 2 weeks after birth, cells in the 1-2 cell layered epithelium proliferate and differentiate to form a 4-5 cell layered stratified squamous epithelium by 20 days after birth. The mature corneal epithelium containing 5-8 cell layers is present by 6 to 8 weeks after birth. Krüppel-like transcription factors KLF4 and KLF5 are among the most abundant transcription factors in the mouse cornea. KLF4 and KLF5 share an identical DNA-binding domain and regulate a diverse array of critical cellular functions. Considering that Klf4-null and Klf5-null mice die before mature cornea is formed, Dr. Swamynathan resorted to conditional deletion of Klf4 and Klf5 gene in the surface ectoderm- derived tissues of the eye (lens, cornea, conjunctiva and eyelids) by mating Klf4-loxP or Klf5-loxP mice with Le-Cre mice. Dr. Swamynathan discovered that Klf4 conditional null (Klf4CN) and Klf5CN mice display normal viability and fertility, and a defective ocular surface. Detailed analysis of their ocular surface phenotype along with identification of the corneal and conjunctival KLF4-target genes as well as corneal KLF5-target genes provided new insights into the non-redundant roles of KLF4 and KLF5 in post-natal maturation of the ocular surface. Dr. Swamynathan plans to pursue this line of work further to understand the molecular basis for diverse functions of KLF4 and KLF5 in maturation and maintenance of the ocular surface.
In a second line of research, Dr. Swamynathan is investigating the ocular surface expression and functions of the secreted Ly6/urokinase plasminogen activator receptor-related protein-1 (Slurp1), associated with the hyperkeratotic disorder Mal-de-Meleda. Slurp1 is one of the most abundantly expressed peptides in the mouse cornea and is secreted into the tear film. In collaboration with the Hendricks and Kinchington labs, the Swamynathan lab demonstrated that Slurp1 expression is (i) increased upon mouse eyelid opening when the cornea is first exposed to the environment, (ii) critically dependent on the transcription factor KLF4, (iii) abrogated within 24 hours of Herpes-Simplex-Virus Type-1 (HSV-1) infection or bacterial lipopolysaccharide injection concurrent with neutrophil infiltration, (iv) decreased in inflamed Klf4CN corneas, and (v) suppressed by pro-inflammatory cytokines IL-4, IL-13 and TNF-. More importantly, Slurp1 expression was significantly reduced in adenoviral keratitis model of corneal inflammation, restoration of which suppressed corneal inflammation, providing convincing evidence in favor of an immunomodulatory role for Slurp1. Dr. Swamynathan is pursuing this line of work further to determine the value of Slurp1 as a target for developing novel therapeutic approaches for managing inflammatory disorders of the ocular surface.

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.
 

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