Research

Our group has pioneered efforts to determine the significance and functions of MUC5AC and MUC5B in the lungs. Using mouse genetic models alongside human tissues and cells, we discovered critical beneficial roles for MUC5B in homeostasis and responses to infection. Conversely, we have also identified required detrimental roles for excessive or aberrant MUC5AC and MUC5B in airflow obstruction, lung injury, pulmonary fibrosis, and lung adenocarcinoma.

Much of our on-going work uses over-expressing, knockout, and gene-edited transgenic mouse lines to address how each mucin functions individually or in combination.  Current research involves investigating how these two mucins perform specific functions – both beneficial and potentially harmful – that can be discerned by precisely determining how the proteins are translated, assembled, and glycosylated.

Specific projects focus on five main questions that apply to mechanisms of host defense, tissue injury, inflammation, and repair.

1. How do MUC5AC and MUC5B polymerize through formation of disulfide bonds between molecules?
   
   
2. How are specific sugars added to MUC5AC and MUC5B under healthy and inflamed conditions?
   
   
3. How does mucin biosynthesis affect epithelial cell protein homeostasis (proteostasis)?
   
   
4. How do secreted mucin glycopolymers affect mucus function?
   
   
5. How do mucins interact with and affect the functions of leukocytes and structural cells in the lungs?