Shivalingappa (Shiva) Swamynathan, PhD

  • Associate Professor of Ophthalmology
  • Ocular Surface Development Laboratory
  • University of Pittsburgh School of Medicine

Academic Affiliation

Associate Professor, Department of Ophthalmology
University of Pittsburgh School of Medicine, Pittsburgh, PA

2015 - Present: Associate Professor, Department of Ophthalmology University of Pittsburgh School of Medicine, Pittsburgh, PA

2007 - 2015: Assistant Professor, Department of Ophthalmology University of Pittsburgh School of Medicine, Pittsburgh, PA

2005 - 2007: Staff Scientist, NEI, NIH

2000 - 2005: Intramural Research Training Associate, NEI, NIH

1996 - 2000: Post-doctoral fellow, University of Missouri-Columbia.

Education & Training

  • University of Agricultural Sciences, Bangalore, India (B.Sc.)
  • Indian Agricultural Research Institute, New Delhi, India (M.Sc.)
  • Center for Cellular and Molecular Biology, Hyderabad, India (Ph.D.)
  • Post-Doctoral Fellowship, University of Missouri-Columbia, National Eye Institute, NIH

Representative Publications

  1. Swamynathan, S., Campbell. G., Tiwari, A., and Swamynathan, S.K.* Secreted Ly-6/uPAR-related protein-1 (SLURP1) is a pro-differentiation factor that stalls G1-S transition during corneal epithelial cell cycle progression. 2021. Ocul Surf. 16; 24:1-11. doi: 10.1016/j.jtos.2021.12.006.  PMID: 34923162
  2. Tiwari, A., Swamynathan, S., Campbell, G., Jhanji, V., and Swamynathan, S.K.* BMP6 regulates corneal epithelial cell stratification by coordinating their proliferation and differentiation and Is upregulated in pterygium. 2020. Invest Ophthalmol Vis Sci. 61(10):46. doi: 10.1167/iovs.61.10.46. PMID:32845956
  3. Tiwari, A., Swamynathan, S., Jhanji, V. and Swamynathan, S.K.* KLF4 coordinates corneal epithelial apical-basal polarity and plane of cell division and is downregulated in ocular surface squamous neoplasia. 2020.  Invest. Ophthalmol. Vis. Sci. 61(5):15. doi: 10.1167/iovs.61.5.15. PMID: 32396634.
  4. Swamynathan, S.K.*, and Wells, A. Conjunctival goblet cells: Ocular surface functions, disorders that affect them, and the potential for their regeneration. 2019. Ocul. Surf. Nov 14. pii: S1542-0124(19)30330-1. doi: 10.1016/j.jtos.2019.11.005. PMID: 31734511.
  5. Campbell, G., Swamynathan, S., Tiwari, A., and Swamynathan, S.K.* The secreted Ly-6/uPAR related protein-1 (SLURP1) stabilizes epithelial cell junctions and suppresses TNF-α-induced cytokine production. 2019. Biochem Biophys Res Commun. 517(4):729-734. PMID: 31387745.
  6. Swamynathan, S., Tiwari, A., Loughner, C.L., Gnalian, J., Alexander, N., Jhanji, V., Swamynathan, S.K.* The secreted Ly6/uPAR-related protein-1 suppresses neutrophil binding, chemotaxis, and transmigration through human umbilical vein endothelial cells. 2019. Sci. Rep. 11;9(1):5898. doi: 10.1038/s41598-019-42437-x. PMID: 30976100.
  7. Tiwari, A., Swamynathan, S., Alexander, N., Gnalian, J., Tian, S., Kinchington, P.R. and Swamynathan, S.K.* KLF4 regulates corneal epithelial cell cycle progression by suppressing canonical TGF-b signaling and upregulating CDK inhibitors P16 and P27. 2019. Invest. Ophthalmol. Vis. Sci. 60(2):731-740. PMID: 30786277.
  8. Loughner, C.L., Tiwari, A., Kenchegowda, D., Swamynathan, S. and Swamynathan, S.K.* Spatiotemporally controlled ablation of Klf5 results in dysregulated epithelial homeostasis in adult mouse corneas. 2017. Invest. Ophthalmol. Vis. Sci. 58(11):4683-4693. PMID: 28910443.
  9. Tiwari, A., Loughner, C.L., Swamynathan, S. and Swamynathan, S.K.* KLF4 plays an essential role in corneal epithelial homeostasis by promoting epithelial cell fate and suppressing epithelial–mesenchymal transition. 2017. Invest. Ophthalmol. Vis. Sci. 58: 2785-2795. PMID: 28549095.
  10. Swamynathan, S., Loughner, C.L. and Swamynathan, S.K.* Inhibition of HUVEC tube formation via suppression of NFkB suggests an anti-angiogenic role for SLURP1 in the transparent cornea. 2017. Exp. Eye Res. 164:118-128. PMID: 28803936.
  11. Loughner, C.L., Bruford, E.A., McAndrews, M.S., Delp, E.E., Swamynathan, S. and Swamynathan, S.K.* Organization, evolution and functions of the human and mouse Ly6/uPAR family genes. 2016. Human Genomics. doi: 10.1186/s40246-016-0074-2. PMID: 27098205.
  12. Swamynathan, S., Delp, E.E., Harvey, S.A.K., Loughner, C.L., Raju, L. and Swamynathan, S.K.* Corneal expression of SLURP-1 by age, sex, genetic strain and ocular surface health. 2015. Invest. Ophthalmol. Vis. Sci. 56:7888-7896. PMID: 26670825.
  13. Delp, E.E., Swamynathan, S., Kao, W.W. and Swamynathan, S.K.* Spatiotemporally regulated ablation of Klf4 in adult mouse corneal epithelial cells results in altered epithelial cell identity and disrupted homeostasis. 2015. Invest. Ophthalmol. Vis. Sci. 56:3549-3558. PMID: 26047041
  14. Swamynathan, S. and Swamynathan, S.K.* SLURP-1 modulates corneal homeostasis by serving as a soluble scavenger of urokinase-type plasminogen activator uPA. 2014. Invest. Ophthalmol. Vis. Sci. 55:6251-6261. PMID: 25168896.
  15. Gupta, D., Harvey, S.A., Kenchegowda, D., Swamynathan, S., and Swamynathan, S.K. * Regulation of mouse lens maturation and gene expression by Krüppel-like factor 4. 2013. Exp. Eye Res. 116: 205-218. PMID: 24076321.
  16. Swamynathan, S.K.* Ocular surface development and gene expression. 2013. J Ophthalmol. 2013: 103947. doi: 10.1155/2013/103947. PMID: 23533700.
  17. Swamynathan, S., Buela, K.A, Kinchington, P., Misawa, H., Lathrop, K.L., Hendricks, R.L. and Swamynathan, S.K.* Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea. 2012. Invest. Ophthalmol. Vis. Sci. 53:8433-8446. PMID: 23139280.
  18. Kenchegowda, D., Harvey, S.A.K., Swamynathan, S., Lathrop, K.L. and Swamynathan, S.K.* Critical Role of Klf5 in Regulating Gene Expression during Post-Eyelid Opening Maturation of Mouse Corneas. 2012. PLoS ONE 7(9): e44771. doi:10.1371/journal.pone.0044771. PMID: 23024760.
  19. Kenchegowda, D, Swamynathan, S, Gupta, D, Wan, H, Whitsett, J, and Swamynathan S.K*. Conditional disruption of mouse Klf5 results in defective eyelids with malformed meibomian glands, abnormal cornea and loss of conjunctival goblet cells. 2011. Dev. Biol. 356:5-18. PMID: 21600198.
  20. Swamynathan, S., Kenchegowda, D., Piatigorsky, J. and Swamynathan, S.K. * Regulation of the corneal epithelial barrier function by Krüppel-like transcription factor 4. 2011. Invest. Ophthalmol. Vis. Sci. 52:1762-1769. PMID: 21051695.
  21. Gupta, D., Harvey, S.A., Kaminski, N. and Swamynathan, S.K. * Mouse conjunctival forniceal gene expression during postnatal development and its regulation by Krüppel-like factor 4. 2011. Invest. Ophthalmol. Vis. Sci. 52:4951-4962. PMID: 21398290.
  22. Swamynathan, S.K.* Krüppel-Like Factors: Three fingers in control. 2010. Human Genomics. 4(4): 1-8. PMID: 20511139.

Research Interests

i. Ocular Surface Functions of KLF4 and KLF5: The adult corneal epithelium (CE) is continually renewed throughout life. The most superficial cells lost by desquamation are replaced by the underlying cells derived from the basal cells which differentiate as they migrate upwards, and in turn are replaced by the peripheral limbal stem cell-derived transient amplifying cells that migrate centripetally. We are interested in understanding the functions of Krüppel-like factors KLF4 and KLF5 that are among the most abundant transcription factors in the adult mouse cornea, in this process. As germline ablation of Klf4 or Klf5 results in premature lethality before mature cornea is formed, we resorted to Cre-Lox-mediated conditional ablation of Klf4 or Klf5 in the ocular surface from embryonic day-9 to study their role in CE maturation, or specifically within the normally formed adult CE in a spatiotemporally regulated manner to study their role in homeostasis. Our studies revealed that KLF4 and KLF5 have profound influence on the ocular surface by regulating CE cell proliferation, differentiation, structural stability, and barrier function, and conjunctival goblet cell formation. We are pursuing this work further to understand the molecular basis for diverse functions of KLF4 and KLF5 in maturation and maintenance of the ocular surface.

ii. Ocular Surface Functions of SLURP1: We are also investigating the ocular surface functions of the secreted Ly6/uPAR-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. Our work demonstrated that Slurp1 expression is (i) increased upon mouse eyelid opening when the cornea is first exposed to the environment, (ii) dependent on the transcription factor KLF4, (iii) abrogated within 24 h of bacterial lipopolysaccharide injection or Herpes-Simplex-Virus (HSV) infection concurrent with neutrophil infiltration, (iv) decreased in inflamed Klf4CN corneas, (v) suppressed by pro-inflammatory cytokines IL-4, IL-13 and TNF-alpha and (vi) decreased in adenoviral keratitis, restoration of which restricted the neutrophilic infiltrate, providing evidence in favor of an immunomodulatory role for Slurp1. We also discovered that Slurp1 serves as a soluble scavenger of the urokinase receptor (uPAR) ligands such as urokinase (uPA), and that SLURP1 has an anti-angiogenic role in the transparent cornea. We are pursuing this work further to determine the value of SLURP1 as a target for developing novel therapeutic approaches for managing inflammatory disorders of the ocular surface.

Research Grants

Current Grants

Grant Number, Funding Institute: R01 EY026533-05 NEI, NIH.
Grant Title: Ocular Surface Functions of KLF4 and KLF5.
Grant Period: 2016-2026.
Role: Principal Investigator


Grant Number, Funding Institute: R01 EY031684-01, NEI, NIH.
Grant Title: Ocular Surface Functions of SLURP1.
Grant Period: 2021-2026.
Role: Principal Investigator
 

Previous Grants

Grant Number, Funding Institute: K22 EY016875 NEI, NIH.
Grant Title: Role of KLF4 and KLF5 in mouse cornea development.
Grant Period: 2009-2011.
Role: Principal Investigator


Grant Number, Funding Institute: K22 EY016875-01S1 NEI, NIH.
Grant Title: American Recovery and reinvestment act (ARRA) Admin. Supplement.
Grant Period: 2010.
Role: Principal Investigator


Grant Number, Funding Institute: R01 EY022898 NEI, NIH.
Grant Title: Corneal Expression and Function of Slurp1
Grant Period: 2013-2018.
Role: Principal Investigator


Grant Number, Funding Institute: PA Lions Sight Conservation & Eye Research.
Grant Title: SLURP1- A Diagnostic Marker and Therapeutic Target for Ocular Surface Disorders.
Grant Period: 2014-2015.
Role: Principal Investigator