Michelle L. Manni, PhD

For over a decade, Manni’s research has been focused on understanding the cellular and molecular basis of pulmonary health and disease. Her scientific training and work have been in multiple facets of pulmonary research (lung immunology, inflammation and injury, physiology, pathology, and redox biology), utilizing murine models of human disease to elucidate novel mechanisms of disease pathogenesis. Specifically, the goal of Manni’s current research is to better understand aberrant immune responses in severe asthma, a subset of disease that is poorly responsive to standard therapies and represents a significant source of morbidity and mortality in the western world. While substantial strides have been made in understanding the type 2-high subset of severe asthmatics, a significant proportion of patients still fail to achieve asthma control and there is an unmet need to identify and characterize non-type 2 immune mechanisms of disease. Manni’s research has suggested that T helper 17 (Th17) cells may be critical for pathogenesis of severe asthma, promoting steroid resistant disease characterized by the accumulation of neutrophils in the lungs. In addition to defining severe phenotypes in asthmatics, her work indicates that distinct molecular pathways may regulate each characteristic asthma endpoint (inflammation, mucus metaplasia, airway hyperresponsiveness). In addition to understanding type 2 low, and non-type 2 mechanisms of severe asthma, she is interested in the disconnect between the degree of inflammation and airway hyperresponsiveness in the asthmatic lung and also defining inflammation-independent drivers of airway hyperresponsiveness.

Overall, Manni’s research broadly focuses on T cell immunity, epithelial cell biology, and lung physiology in severe asthma and acute exacerbations. Understanding the pathophysiological mechanisms underlying disease in the less studied clinical subsets of severe asthma is of great interest to her group. Her long-term goal is to improve our scientific knowledge on the different underlying causes of severe asthma to aid in the development and design of more targeted and effective asthma therapies.