Regenerative pharmacology
Although a common and highly morbid disease, no disease modifying therapies are currently available for patients with COPD. Our primary interest in understanding endogenous lung repair and regeneration in the context of COPD pathophysiology with the ultimate goal of developing therapeutics aimed at filling the major gap in therapy for this chronic lung disease. We have on-going projects studying the stem and progenitor cells of the lung epithelium including the pathways driving stemness and differentiation in this population. We are currently developing an organoid modeling system derived from patient donor lung samples to better characterize the patient and disease specific changes to these cell populations, how this dysfunction might affect native regenerative process, and importantly where therapeutics might be able to intervene.
Human tissue derived Precision-Cut Lung Slices (PCLS) as a tool to study extracellular matrix turnover during fibrosis
Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by increased extracellular matrix (ECM) deposition, distorted cell differentiation and function, and impaired lung regeneration. Histological analysis of IPF samples demonstrates increased deposition of ECM around “fibroblast foci” in areas of fibrosis.
Recent studies have demonstrated the dynamic nature of the ECM, which contains specific cues instructing cell fates and function, such as adhesion, proliferation, survival, polarity, migration, and differentiation. However, cell response is not just influenced by ECM composition but also responds to its biomechanical properties, such as stiffness.
By using a combination of profibrotic growth factors and proinflammatory signaling molecules we developed an ex-vivo model in patient-derived PCLS which recapitulates the characteristics of early pulmonary fibrosis, including upregulation of a variety of ECM molecules as collagens and proteoglycans. The goal of this project is to investigate the changes associated with ECM during disease onset and progression.