1) Role of innate immunity in the pathogenesis of fibrotic lung diseases, and nanoparticle delivery systems as therapeutics to treat related disorders.

Hermansky-Pudlak Syndrome (HPS) is a group of inherited autosomal recessive disorders caused by genetic mutations that alter the trafficking of lysosomal-related organelles/vesicles. In a subset of patients with HPS-1 and HPS-4, pulmonary fibrosis develops in the fourth or fifth decade of life, and is a major cause of morbidity and mortality. Experiments proposed in this project will define the cellular and molecular mechanisms of CHI3L1 receptor system, and whether CHI3L1 and its receptor systems are plausible targets to treat HPS-associated lung disease.

2) Pathogenesis of abnormal pulmonary vascular remodeling and the development of pulmonary hypertension.

Pulmonary fibrosis is characterized by chronic, progressive accumulation of scar tissue in the lung. Pulmonary hypertension (PH) is a common and deadly complication of pulmonary fibrosis with unknown causes and no effective treatment option. Experiments proposed in this project will determine whether CHI3L1 and its receptor systems are therapeutic targets to treat vascular remodeling and PH in pulmonary fibrosis.

3) Innate Type 2 immune responses in normal pulmonary homeostasis and injury and repair.

Type 2 immune responses are well documentedin normal homeostaticand immune responses in the lung. Recent studies have highlighted the importance of innate type 2 immune responses and innate lymphoid 2 cells (ILC2s) in disorders such as asthma, allergy, and pulmonary fibrosis. These studies will provide new and critical insights into biology and disease pathogenesis and identify novel targets that can be manipulated in attempts to control Type 2 inflammation in chronic diseases such as asthma.

4) Novel host genes and cellular pathways modulating respiratory viral infections.

Influenza A virus (IAV) is a single-stranded RNA virus that has caused several major pandemics in human history. Unfortunately, current anti-flu drugs targeting viral proteins have led to a significant increase in drug-resistant virus variants. Thus, it is important to understand host-viral protein interactions to design anti-flu drugs that target host factors. Our research may shed light on virus-host interactions and aid in the development of anti-flu drugs.