MSTP in PhD Training
Current advisor: Deborah J. Lenschow, MD, PhD
Undergraduate university: Dartmouth College, 2018
Enrollment year: 2019
ISG15 as a Regulator of Cell Death
The innate immune system responds to a variety of pathogenic and sterile insults through the activation of inflammatory pathways and recruitment of immune cells to clear pathogens and repair tissue. Innate immune signaling is extensively connected to programmed cell death (PCD) pathways, including apoptosis, necroptosis, and pyroptosis. Apoptosis is a “silent” cell death, mediated by caspase-dependent cleavage of executioner caspases. Necroptosis and pyroptosis are forms of “inflammatory” cell death, due to the release of damage-associated molecular patterns (DAMPs) and pro-inflammatory cytokine production upon their induction. Necroptosis is driven by RIPK1/RIPK3-dependent activation of the executioner mixed lineage kinase domain-like (MLKL) protein. Pyroptosis is driven by activation of caspase-1 which cleaves the executioner gasdermin D (GSDMD). These forms of PCD are very important for maintaining homeostasis, pathogen defense, cancer, and a variety of other pathologies.
Our lab has shown that interferon-stimulated gene 15 (ISG15) acts as a negative regulator of necroptosis during murine chikungunya virus infection. ISG15 is an ubiquitin-like interferon-stimulated gene that functions as an antiviral protein and has roles in regulating the host damage and repair response. My research explores the role of ISG15 as regulator of cell death due to both pathogenic and sterile insults. I am focused on elucidating how ISG15 regulates necroptosis and other cell death pathways.