Joseph P. Mizgerd, ScD, Awarded $2.9 Million to Better Understand Pneumonia

Joseph Mizgerd in dark suit white shirt dark tie, head and shoulders imageJoseph P. Mizgerd, ScD, the Jerome S. Brody, MD, Professor of Pulmonary Medicine, and director of the Pulmonary Center, has been awarded a four-year, $2.9 million RO1 grant from the NIH’s National Heart, Lung, and Blood Institute (NHLBI) for his research “Fibrin in the Infected Lung.”

A major unmet goal in pulmonary medicine is to distinguish pneumonia sub-phenotypes responsive to host-directed therapies. Some people who died with pneumonia have abundant fibrin (a fibrous protein involved in the clotting of blood) in their airspaces while others show little or none. Similarly, some experimental models that have pneumonia exhibit lungs with abundant airspace fibrin, while others do not.

“While fibrin in the airspaces is a recognized pathological feature of pneumonia, this heterogeneity is not. Because fibrin can be pro-inflammatory and neutrophils (a type of white blood cell) can enhance fibrin accumulation, we propose the central hypothesis that fibrin and neutrophils in the airspaces form a positive feedback loop that causes damage in a subset of pneumonias,” explains Mizgerd.

Mizgerd’s research focuses on lung immunology and respiratory infection with broad goals of elucidating pathways that determine pneumonia susceptibility and outcome. He began his career as a principal investigator with investigations of the transcriptional and post-transcriptional regulation of immune responses to lung infection, helping to delineate mechanisms of immune resistance and tissue resilience that together protect an infected lung. His more recent findings emphasize how recovery from respiratory infections changes the immune system localized within the lung, including resident memory lymphocytes and trained innate immunity.

Mizgerd says this study will help elucidate the mechanisms and significance of high fibrin accumulation in the airspaces of infected lungs. Results will be informative for whether, and which, subsets of pneumonia patients may respond favorably to host-directed therapies like thrombolytics or anticoagulants that target the polymerized fibrin meshwork.

Mizgerd received his undergraduate degree in biology from Amherst College and then completed research training and served on the faculty at Harvard T.H. Chan School of Public Health. His doctoral studies of lung phagocytes were mentored by Joseph D. Brain, ScD, who was the Cecil K. and Philip Drinker Professor of Environmental Physiology at Harvard; his postdoctoral fellowship studying neutrophil recruitment was mentored by Claire M. Doerschuk, MD, who is now a professor of medicine at the University of North Carolina-Chapel Hill School of Medicine. Mizgerd joined BU as a professor in 2008.