We have two areas of research at our lab. 

Our first translational focus is the study of alveolar type II cell function. These cells have stem cell potential in the adult lung and produce and secrete pulmonary surfactant. They also proliferate to restore epithelial tissues after damage. They then differentiate into alveolar type I cells, which play a critical role in gas exchange in the lung.  

We isolate alveolar type II cells from human and murine (mouse) lungs to investigate the impact of exposure to various factors. These include cigarette smoke, e-cigarette aerosols, and bacterial and viral infections. Our goal is to define mechanisms of cell injury and identify factors that promote alveolar epithelium repair, which can stimulate lung regeneration. 

Secondly, we are investigating the development and progression of pulmonary emphysema. Smoking is a primary risk factor for this disease, which is characterized by the loss of alveolar structure and enlargement of air spaces.  

Because emphysema treatments are limited, we seek a deeper understanding of this disease’s development, leading to novel approaches that slow the destruction of alveolar walls and disease progression. Our research is complemented by studies using cellular, molecular biology, and biochemistry approaches to determine strategies that can promote lung regeneration.  

We study the development and progression of lung diseases, with a particular focus on idiopathic pulmonary fibrosis and emphysema. In particular, we investigate the mechanisms underlying these conditions, including the dysfunction of alveolar epithelial cells.  

Our goal is to explain which processes drive disease development so we can identify novel therapeutic targets. To achieve this, we use human tissue samples in our research, ensuring that our findings are directly applicable to clinical settings.  

Our projects hold clinical significance by:  

1. Studying the mechanisms of DNA damage and repair in primary alveolar type II cells. We seek to understand how these processes contribute to respiratory abnormalities. 
2. Identifying early biomarkers for lung disease development, which can aid in early diagnosis and intervention. 
3. Evaluating the efficacy of potential drugs and provide critical insights into their therapeutic applications. 
4. Exploring the regenerative potential of alveolar type II cells, which could lead to therapies that harness their ability to repair the lung.  
5. Employing single-cell RNA sequencing and proteomics to identify dysregulated pathways in lung diseases. These cutting-edge techniques allow us to pinpoint specific molecular changes and targets for intervention. 

These comprehensive approaches ensure our findings are robust and applicable to real-world scenarios. 

We research inflammatory mechanisms in skin and barrier tissues to develop deeper insights that could help with hard-to-treat skin and barrier tissue inflammation. 

Our main projects are: 

1. HSV-1 protein UL56 in infectivity and pathogenesis — UL56 is a protein encoded by the herpes simplex virus-1 (HSV-1) viral genome. Mice infected with a mutant virus that lacks UL56 don’t die after getting a lethal dose of wild-type virus. We are researching the mechanisms behind the mutant virus’s vaccine-like activity.   
2. Regulation of barrier immunity by the IL-36 system — We have identified how the three IL-36 cytokines promote skin inflammation and are investigating which cells respond to IL-36. Our lab-developed mouse strain allows us to trace receptor expression in multiple organs, including the skin, lungs, oral cavity, and digestive system. Ongoing studies are examining the role of the IL-36 receptor in diseases affecting these organs. 
3. Pellino1 as a critical regulator of antiviral immunity — This ubiquitin ligase  regulates several intracellular signaling pathways. Recently, we showed that mice lacking this protein are more susceptible to HSV-1 infection. Currently, we are examining which cells and pathways are regulated by Pellino1. 

We investigate molecular mechanisms that regulate proinflammatory signaling in the innate immune system. In particular, we look at the role of leukocytes in vascular inflammation and development of organ injury in sepsis. Current work is focused in two areas:  

1. Identifying distinct immune cell phenotypes in sepsis patients. We are studying the effect of different neutrophil phenotypes in sepsis and the mechanism by which different functional neutrophil phenotypes impact neutrophil-endothelial interaction, vascular barrier permeability, and neutrophil trafficking into critical organs. These ex vivo studies use organ-on-chip assays, proteomics, and in silico modeling to provide mechanistic insight into the impact of different neutrophil phenotypes on cell activation, unique proteomic signatures, barrier permeability, and neutrophil trafficking.   
2. Determining of the impact of sepsis patient neutrophil phenotypes on the ex vivo response to therapeutics. We are using in silico modeling to identify FDA-approved drugs that target differentially expressed proteins within and across different neutrophil functional phenotypes. These drugs are then experimentally validated in our organ-on-chip systems. Recognition of diverse functional neutrophil responses may provide insight for patient stratification in clinical trials and identify novel therapeutic targets for specific patient populations. 

We are investigating airway epithelial regeneration and innate immune function. 

If the lining of the airways — the epithelium — is injured by disease or inhaled pathogens, lung tissue-specific stem cells normally can repair them. However, in conditions such as chronic obstructive pulmonary disease (COPD), epithelial cells don’t regenerate normally. They also produce more mucus, which can obstruct the airways. In people with COPD, epithelium reacts abnormally to viruses like the common cold. We’ve also found a lower level of developmental genes in COPD airway stem cells. However, we don’t yet know how these genes affect airway epithelial regeneration. Understanding more about them may lead to COPD treatments. 

We are also doing clinical trials to investigate treating COPD with a natural compound called quercetin, which has potent anti-inflammatory and antioxidant properties. A small Phase II clinical trial indicated that, in a majority of cases, quercetin reduces lung inflammation and oxidative stress and improves respiratory symptoms in these patients. 

Also, COPD patients’ airway stem cells showed elevated expression of genes that may participate in healing the airway lining. Another small phase II clinical trial is investigating these findings. We also use samples from placebo and quercetin-treated patients to understand the mechanisms underlying the benefits of quercetin in COPD.