This research group is focused on understanding immunity and immune dysfunction in both acute and chronic lung illness. The group uses pre-clinical animal models to unravel mechanisms that drive immunopathology in infectious and allergic disease.
These studies are then supported by translational studies conducted at UPMC’s hospital system. The overall goal is to identify beneficial versus detrimental immune activation in lung disease with an emphasis on future biologic therapies.
Current Projects
- Severe, steroid resistant asthma
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Principal Investigator – Michelle L. Manni, PhD
This NIH-funded project is focused on understanding how T lymphocytes drive allergic asthma. The majority of asthma health care costs are associated with severe asthma of which approximately half do not reflect classical Type 2 high immune activation. In this project, advanced pre-clinical models have been developed to test distinct asthma endotypes and potential interventions.
- Immunity in influenza and bacterial super-infections
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Principal Investigator – John F. Alcorn, PhD
Complication of primary influenza infection with secondary bacterial pneumonia results in a potentially life-threatening illness. Less attention has been paid to complex acute polymicrobial infections. This NIH-funded research is focused on understanding how viruses increase susceptibility to secondary infections, how immunity is altered in super-infections, and investigating potential therapeutics in pre-clinical animal models.
- T cell immunity in response to influenza vaccination
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Principal Investigator – John F. Alcorn, PhD
This CDC-funded project is focused on understanding cell-mediated immunity following vaccination in children and older adults. Antibody response to vaccines is a classic measure of efficacy; however, antibody is strain-specific and may be impacted by pre-existing immunity and durability. T cell immunity is thought to provide heterotypic strain immunity that is desirable as universal influenza vaccines are developed. Recently, these studies have been extended to SARS-CoV-2 vaccine recipients.
- Influenza related cardiovascular sequelae
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Principal Investigator – Radha Gopal, PhD
This NIH-funded project is focused on understanding immune mechanisms that drive atherosclerosis and myocarditis during influenza infection of the lung. Myocardial infarction is an important complication associated with severe influenza and little is known about the immune mechanisms of disease. In this study using pre-clinical animal models, the molecular pathways involved in inflammation distal to the lung are studied.
- Computational modeling of severe influenza infection
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Principal Investigator – John F. Alcorn, PhD
The translational project is focused on studying influenza severity in pre-clinical animal models and human beings. Supported by the NIH, CDC, and University of Pittsburgh CTSI, this study examines the range of outcomes of influenza infection, from mild to severe, in outbred animals and in children and adults. Immune data are collected and used for machine learning and computational analyses to identify predictive biomarkers of severe disease progression and drivers of immunopathology.