Shivalingappa Swamynathan, PhD

Dr. Shivalingappa (Shiva) Swamynathan is an Associate Professor with the Department of Ophthalmology in the University of Pittsburgh School of Medicine. He also holds a secondary appointment as an Associate Professor in the Department of Cell Biology, University of Pittsburgh.

Dr. Swamynathan received his BSc at the University of Agricultural Sciences in Bangalore, India. He earned his Master’s in Molecular Biology and Biotechnology at the Indian Agricultural Research Institute in New Delhi. From there he went to the Center for Cellular and Molecular Biology for his PhD. He left India when he won a research fellowship at the University of Missouri-Columbia, Department of Molecular Microbiology and Immunology. He then accepted a post at the National Eye Institute, where he was first an Intramural Research Training Associate and then a Staff Scientist.

Dr. Swamynathan is interested in understanding the regulation of gene expression during maturation and maintenance of the 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 is pursuing 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-a. 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.

Dr. Swamynathan is a member of the American Association for the Advancement of Science, and the Association for Research in Vision and Ophthalmology. He has received numerous honors, including the National Eye Institute Career Development (K22) Award, the Best Scientific Paper, 2009 Asia-ARVO Meeting, and the Indian National Merit Fellowship. He serves as an Editorial Board Member for the Journal of Ophthalmology, and is an ad hoc reviewer for many journals, such as the Journal of Molecular Biology, Development, Developmental Biology, Experimental Eye Research, and Investigative Ophthalmology and Visual Sciences, amongst others. Ongoing work in the Swamynathan Lab is supported by an RO1 grant from the National Eye Institute, NIH.

View a list of Dr. Swamynathan’s publications here.