Funding: Our lab receives funding from the Department of Defense and NIH/NHLBI.
Ceramide Induced destruction in Emphysema
COPD has been shown to be linked to a stress-induced cellular repair process called autophagy, however little is known on how cigarette smoke exposure disrupts the stepwise process of autophagy. This project aims to better understand the effects of cigarette smoke exposure on autophagy as well as to identify mechanisms that enhance the survival and the repair of lung microvascular endothelial cells. Our lab previously uncovered two sphingolipid rheostats (sphingosine/S1P and ceramide/glucosylceramide) that are disrupted by cigarette smoke resulting in the dysregulation of the autophagic flux. We hypothesize that restoration of the sphingolipid rheostat is required for complete lysosomal autophagy and the repair of cigarette smoke-induced lung microvascular endothelial cells.
Lung Repair by Tetraspanin Interacting Protein IGSF3
Immunoglobulin Superfamily 3 protein (also referred to as IGSF3) is a multi-functional membrane-bound cell adhesion molecule that interacts with a family of membrane-spanning proteins called tetraspanins. This family of proteins form membrane platforms called tetraspanin-enriched microdomains (TEMs). The goal of this project is to better understand the function of IGSF3 (and its interactions with tetraspanins) in alveolar epithelial and capillary endothelial cells and how this protein contributes to lung injury such as emphysema and asthma. This project builds off our lab’s previous discovery of a novel translocation within the coding region of IGSF3 in a patient with severe emphysema and is required for cell migration and endothelial barrier function. We hypothesize that IGSF3-protein interactions, tethered by tetraspanins, contribute to the maintenance of the lung barrier, and can be modulated by extracellular stimuli such as cigarette smoke.
Biomarkers induced by e-cigarette vapor exposures in the human distal lung
- With the increasing prevalence of vaping in young communities, we investigated potential biomarkers induced by e-cigarette smoke that would indicate both cell injury as well as an increased risk for respiratory viral infection. This project examines the impact of reactive oxygen species, aldehydes, flavorings, and other small molecules that could play a role in the level of severity of lung injury. Our research extends to how the resulting inflammatory response affects the lung injury. We hypothesize that E-Cigarette vapor induces defective intracellular acidification in human distal lung structural cells, generating molecular bioindicators of distal lung injury and amplified inflammatory response to respiratory virus infections.
Ceramide mediates COVID-19 vascular injury and ARDS
In a collaboration with the laboratory of Richard Kolesnick, MD (Memorial Sloan Kettering Cancer Center), we are investigating the mechanisms regulating the peptide hormone, Angiotensin 2 mediated acid sphingomyelinase activation. We hypothesize that this signaling pathway is critical for the pulmonary vascular dysfunction and resulting acute lung injury caused by SARS-CoV-2 in human lung endothelial cells.
Pathogenesis of pulmonary hypertension in COPD
Pulmonary Vascular Remodeling (PVR), changes in the vessels in the lungs, can come from chronic cigarette smoking (CS). With PVR being directly linked to type 3 pulmonary hypertension, it can be assumed then that CS alone is a risk factor for the development of pulmonary hypertension. By looking at how endothelial cells are changed by CS, the lab aims to investigate the development of PVR as well as giving us the possibility to identify new biomarkers for those at risk for type 3 pulmonary hypertension and treatments to restore main function in the lungs.