Gowri Kalugotla

Program: Molecular Microbiology and Microbial Pathogenesis

Current advisor: Megan T. Baldridge, MD, PhD

Undergraduate university: Yale University, 2016

Enrollment year: 2018

Research summary
Investigating the role of epg-5 in intestinal antiviral signaling

EPG5 is essential for the maturation of autophagosomes into degradative autolysosomes as a key step in basal autophagy, which has well established pro- and antiviral functions during viral infection. Investigating autophagy-virus interactions will lead to a deeper understanding of this fundamental cellular process as well as viral pathogenesis. We previously found that Epg5-/- mice are resistant to murine norovirus and rotavirus, models for common enteric viruses with a high global burden of disease.

Interferon (IFN)-λ, which restricts viral infection at mucosal sites, is dysregulated in uninfected Epg5-/- mice, which causes overexpression of IFN stimulated genes (ISGs) and drives the viral resistance we observe in these mice. Although the cause of IFN dysregulation in Epg5-/- mice remains to be elucidated, investigation in mice is practically restricted by the non-Mendelian ratios of Epg5-/- pups obtained from heterozygous breeders.

In search of a more tractable system, we found that epg-5-mutant Caenorhabditis (C.) elegans are also resistant to the nematode-specific Orsay virus, which infects intestinal cells. Although C. elegans lacks IFNs, many elements of innate immunity are conserved in the C. elegans intracellular pathogen response (IPR), similar to ISGs in vertebrates. My current work is focused on elucidating the mechanism by which epg-5 mutation causes antiviral resistance in C. elegans.

Graduate publications
Ingle H, Hassan E, Gawron J, Mihi B, Li Y, Kennedy EA, Kalugotla G, Makimaa H, Lee S, Desai P, McDonald KG, Diamond MS, Newberry RD, Good M, Baldridge MT. 2021 Murine astrovirus tropism for goblet cells and enterocytes facilitates an IFN-λ response in vivo and in enteroid cultures. Mucosal Immunol, 14(3):751-61. PMCID: PMC8085034

Lee S, Kalugotla G, Ingle H, Rodgers R, Wu C, Wang Y, Li Y, Yang X, Zhang J, Borella NR, Deng H, Droit L, Hill R, Peterson ST, Desai C, Lawrence D, Lu Q, Baldridge MT. 2021 Intestinal antiviral signaling is controlled by autophagy gene Epg5 independent of the microbiota. Autophagy, ():1-16. PMCID: PMC9196718

Walker FC, Hassan E, Peterson ST, Rodgers R, Schriefer LA, Thompson CE, Li Y, Kalugotla G, Blum-Johnston C, Lawrence D, McCune BT, Graziano VR, Lushniak L, Lee S, Roth AN, Karst SM, Nice TJ, Miner JJ, Wilen CB, Baldridge MT. 2021 Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. PLoS Pathog, 17(3):e100940. PMCID: PMC7987144