The Kopp laboratory focuses on host-pathogen interactions that impact chronic respiratory diseases such as cystic fibrosis (CF) and lung disease related to sickle cell. The two main areas of this research include how immune cells called macrophages fail to regulate infection in chronic lung diseases as well as elucidating biomarkers/pathways of early inflammatory airway disease. We use the information gained to help develop novel therapeutics and targets to allow for improved killing of bacteria and regulation of hyper-inflammatory signaling in chronic respiratory diseases.
Cystic fibrosis (CF) is an under-recognized immunodeficiency. Lung disease in CF begins in early infancy due to deficiencies in cystic fibrosis transmembrane conductance regulator (CFTR) function. This dysfunction leads to the production of dehydrated mucus, impaired immunity, and subsequent acute and chronic infections that cause progressive structural and functional changes in the respiratory tract. However, no definitive cure for CF exists, including standard ways to improve immune-mediated clearance of bacteria. Although advances in CF knowledge and care (i.e., CFTR modulators) have improved clinical outcomes, patients with CF remain burdened by chronic, multi-drug-resistant bacterial infections. There is a clear need for NEW therapeutics approaches to infection in CF.
Sickle cell disease (SCD) affects millions of people worldwide, and primarily impacts underserved populations. To date, little is known about how lung disease occurs in patients with SCD. Of the different complications associated with SCD, acute chest syndrome (ACS) is a significant cause of morbidity and premature death. ACS results in a severe pneumonia-like picture and is the second most frequent cause of hospitalization for patients with SCD behind pain crises. Despite the frequent and severe nature of ACS, the tools to identify patients at risk of developing this syndrome are lacking. Further, limited studies have attempted to determine immune responses that occur during ACS. There is a clear need for NEW therapeutic approaches to ACS in SCD.
Cure Cystic Fibrosis Columbus (C3) Immune Core
Patients with CF are prone to infections by several pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Burkholderia cenocepacia, and non-tuberculosis Mycobacteria. CF patients also have hyper-inflammatory responses, which are associated with tissue damage. Therefore, it is now recognized that CF immune cells such as macrophages, neutrophils, and T cells are intrinsically dysfunctional. Our services will support projects and C3 members who seek to understand complex CF host-pathogen interactions and inflammation and thereby develop novel therapeutic strategies that prevent the establishment of chronic infections and tissue destruction. The immune core will facilitate this research through 1) the isolation and analysis of live immune cells, including live neutrophils, lymphocytes, monocytes, and monocyte-derived macrophages from the blood of patients with and without CF. Isolation of alveolar macrophages and neutrophils from bronchoalveolar lavage (BAL) and tissue-resident macrophages from parenchymal explanted lung tissue will be also provided to laboratories. 2) Chemokine and cytokine measurements of BAL samples or whole blood will be performed. Finally, 3) Functional analysis including halide efflux and patch-clamp electrophysiology for CFTR and other ion channels within immune cells.
Contact Dr. Kopp for more information on the C3 Immune Core.