Researchers supported by the center use a variety of approaches to characterize the changes in activities of each of the cell types that make up the community – the epithelial cells, the macrophages, the neutrophils, etc. – and in the signals by which they communicate within the community, to identify those changes (including biomarkers of a variety of molecular categories) that are associated with progressive lung disease. A goal of the center is to apply systems biology approaches and computational modeling to understand how these components of the community interact. These approaches will identify new therapeutic routes. Center researchers also will collaborate with engineers to design a device that monitors the airway of CF patients for those changes, which will allow CF clinicians to recognize the warning signs of impending pulmonary decline in order to initiate aggressive treatment.
The three disease foci for our CF research program are:
- Early CF Lung Disease – understanding the fundamental differences in the infant CF airway that predispose to infection
- CF Diabetes – understanding how failure to control blood glucose levels markedly accelerates the progression of lung disease in CF patients
- Acute Pulmonary Exacerbations – identification of biomarkers of oncoming acute exacerbations and development of devices to monitor them
These foci address the concept of CF as a progressive disease. CF disease begins with baseline risk (i.e., genotype), modified by environmental factors such as socioeconomic status. Pulmonary disease worsens through the successive occurrence of acute pulmonary exacerbations (APEs) which result in the accumulation of irreversible lung damage. It is known that addressing a progressive disease like CF late in the course of disease results in higher costs and decreased reversibility; consequently, decreased quality and length of life. In contrast, intervening in the disease process early results in slower disease progression, increased quality of life, decreased hospitalizations, and decreased costs of intervention.
As a consequence of this research program, we hope to be able to intervene early, as a CF patient with established disease transitions from preclinical to clinical status with each acute pulmonary exacerbation, as the newborn begins to show signs of airway colonization by the Pseudomonas bacteria, and as the adolescent starts to show signs of CF-related diabetes, thus improving pulmonary outcomes. This will enable Prospective Healthcare for CF patients: an approach to healthcare that is proactive, predictive, preventative, participatory, and personalized to the relevant stage of life with the disease.
The four scientific foci for our CF research program are:
- Systems Biology
- Redox Stress
- Innate Immunity
- Drug Discovery/Development
These approaches reflect a series of strengths at Emory, Georgia Tech, and Children’s which will make it possible for us to focus on keeping CF patients healthy via efforts to prevent the development of full-blown disease and by providing our patients and physicians tools to maintain health.