Alessandro Venosa, PhD, PharmD

My laboratory focuses on two major projects: understand lung epithelial-immune cell crosstalk in homeostasis and injury; investigate the effects of air pollution on susceptible populations. To address these research questions, we leverage a novel murine model of spontaneous pulmonary fibrosis driven by mutation on the surfactant protein C gene. Immune cell lineage tracing techniques are also used to monitor inflammatory cell dynamics during lung injury.

1) Idiopathic pulmonary fibrosis (IPF) represents the most common subtype of interstitial lung diseases (ILDs) of unknown etiology in adults. The incidence of IPF is increasing, with higher frequency in men and aged populations. Family-based studies have led to the identification of rare variants in genes related to surfactant function and telomere biology. Alveolar epithelial type II cell dysfunction represents the cornerstone of the PF phenotype. More than 60 mutations of the epithelial cell–restricted gene coding for surfactant protein C (SP-C), have been described in PF. The missense substitution of isoleucine to threonine at position 73 (SP-C^I73T) is the most common. To study epithelial-driven stress and its downstream inflammatory effects, we generated a murine model expressing inducible levels of SP-C^I73T. We are interested in understanding how epithelial and immune cells communicate during acute and chronic lung injury, with particular emphasis on the role of AT2-monocyte, AT2-alveolar macrophage, and AT2 eosinophil communication. Using high throughput techniques (bulk and single cell RNA-sequencing, metabolomics, lipidomics) we are investigating signaling pathways involved in this crosstalk which could hold therapeutic value in pulmonary fibrosis.

2) Environmental exposure is known to exacerbate the functional decline observed in the elderly, individuals with preexisting conditions, and those presenting genetic mutations affecting parenchymal function (i.e. SP-C^I73T). Ozone is a ubiquitous air pollutant known to irritate and damage the lung parenchyma and trigger immune cell activation. To model the effects of chemical exposure on a “less-than-perfect” lung, we study the effects of ozone (O₃) in the SP-C^I73T murine model. The ultimate goal for these studies is to: 1) characterize signaling pathways uniquely triggered by O₃in SP-C^I73T mice; 2) elucidate how SP-C^I73T mutation respond to more persistent inhaled pollutants, including particulate matter, and smoke (wildfire, cigarette and e-cigarettes); and 3) examine the effects that aging has on air pollution, both alone or in combination with parenchymal mutations.