My research program is on innate immunity with an emphasis on the role of neutrophils as immune regulatory cells in host defense. Specifically, my lab examines the immune response to parasitic, bacterial and fungal pathogens that cause blinding infections of the cornea (keratitis). I received funding from the National Eye Institute (NEI) to study ocular onchocerciasis (river blindness) for 15 years, where we found that endosymbiotic Wolbachia bacteria mediate the inflammatory response in the cornea (Science 2002). We have had NEI support to study innate immunity in bacterial infections since 2002, and to examine fungal corneal infections since 2008. My lab identified neutrophil mediators that control infections caused by Aspergillus fumigatus, Pseudomonas aeruginosa or Streptococcus pneumoniae, which include reactive oxygen species, iron and zinc chelators that compete with pathogens for essential metals and nutrients. Most recently, and most relevant to the candidate’s application, and have demonstrated a role for neutrophil extracellular traps (NETs). Collaborative projects have also enabled us to identify virulence factors of Aspergillus and Fusarium species that cause keratitis, and to identify the role and mechanism of action of the P. aeruginosa Type III secretion system in corneal infections.
We have also characterized the role of neutrophils as immunoregulatory cells, including the highly pro-inflammatory cytokine IL-1b. We reported that neutrophils are not only an important source of IL-1b in response to infection with these pathogenic fungi and bacteria, but also that neutrophils have a functional NLRP3 inflammasome that is essential for processing the pro-form of IL-1b to the bioactive form of this cytokine in the absence of pyroptosis. Our recent studies also examined the role of the pore forming protein Gasdermin-D (GSDMD) in neutrophil IL-1b secretion (Nature Communications 2020), and that IL-1a is secreted in exosomes (Cell Reports 2021).
I have been continuously involved in advancing the next generation of scientists, as illustrated by my track record of having successfully trained 19 post-doctoral fellows (14 in the last ten years), and 9 graduate students. Three of my graduate students and one of my post-docs received NIH Ruth L. Kirschstein fellowships (F30, F31, F32), and most of my students received travel awards to present their research at national and international conferences.
Contact: epearlma@uci.edu