Zdenek Hel, Ph.D., Professor, Molecular and Cellular Pathology, has been awarded with a School of Medicine COVID-19 research grant. The $40,000, one-year award will allow Dr. Hel to study the development of acute respiratory distress syndrome (ARDS), a predictor of high mortality, in COVID-19 patients.
Hel's project aims to investigate the accumulation of neutrophils in the lungs which he hypothesizes leads to the development of ARDS, and serves "as drivers of pathogenesis and mortality" in those patients.
Dr. Hel is a senior scientist with the Inflammation, Immunology and Immunogenomics section of the O'Neal Comprehensive Cancer Center; an associate scientist, Center for AIDS Research, and a scholar with the Sparkman Center for Global Health. He is an assistant professor in Microbiology.
His project hypothesizes that elicited neutrophil populations that accumulate in the lungs of infected patients have a high capacity to undergo NETosis and to promote the progression of ARDS and end-organ damage. From the award-winning proposal:
"This hypothesis has been formulated on the basis of our preliminary data and recently published reports demonstrating the role of neutrophils in the progression of COVID-19. The objectives of this proposed work are to define the roles of neutrophils and NETosis as driving mechanisms of ARDS and end-organ damage in SARS-CoV-2-infected individuals, to identify diagnostic markers of the emergence of pathological neutrophil populations, and to establish checkpoints for intervention."
Hel and his team plan to 1) determine, for SARS-CoV-2-infected individuals, whether the emergence of pathological neutrophil subpopulations and elevation of plasma markers of NETosis are predictive of disease severity.
The project's second aim is characterize the biological properties of neutrophil populations in SARS-CoV-2 infections.
Hel and his team propose using newly developed CITE-Seq technology, which provides simultaneous single-cell anaylsis of RNA expression and levels of surface protein markers, to test the hypothesis that acute SARS-CoV-2 infection induces pathological neutrophil populations with specific gene expression programming.
"A clear definition of the role of neutrophils in SARS-CoV-2 infections will result in the design of new therapeutic approaches for pharmacologically targeting neutrophil dysregulation and development, Hel says. "The findings of this effort are expected to have an immediate translational impact and open avenues for innovative treatments of Covid-19."