Investigator, Asst Prof (M) Mucosal Immunology and Biology Research Center, Mass General Research Institute

Assistant Professor of Pediatrics Harvard Medical School

3'5'-cyclic-gmp phosphodiesterases; cell separation; cystic fibrosis; cystic fibrosis transmembrane conductance regulator; embryonic stem cells; epithelial cells; induced pluripotent stem cells; lung; multipotent stem cells; pulmonary disease; rare diseases; smad proteins; thyroid gland; tissue scaffolds Cystic fibrosis (CF) is the most common lethal monogenetic disease in the Caucasian population. It is a heterogeneous disease with over 1,500 identified genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). As a result, patients exhibit a wide range of clinical manifestations.

There is no cure or effective therapy for over 90% of CF patients. Recent discoveries as well as FDA approval of medications that help to correct the underlying defect in CF are promising. Looking forward, a personalized medicine approach will be essential to the identification of the best therapeutics for each individual patient.

A readily available and renewable supply of human CF airway cells is vital to future drug discovery efforts. Stem cells have the ability to self-renew and generate a variety of daughter cells with specialized functions.

In theory, these characteristics allow airway stem cells to be utilized as a replacement therapy for cells that carry genetic mutations (such as CF) or have been damaged due to injury or disease. These traits also allow stem cells to serve as a source of specialized airway cells that are the gold standard for the study of CF physiology and drug screening.

The laboratory of Hongmei Mou, PhD, aims to generate in vitro human model systems representative of lung diseases. These models, named airway and lung in a dish, are derived from patient and disease-specific airway and lung tissues, or from induced pluripotent stem cells (iPSC), and will possess characteristic physiological functions.

Our lab has developed a novel method to convert normal and diseased iPSCs into lung epithelial stem cells that can both self-renew and give rise to multiple differentiated airway and alveolar cells. In addition, we have established a reproducible culture system in which primary airway and lung stem cells can be expanded without suffering loss of stemness or differentiation potential.

We employ a two-pronged approach to study pulmonary disease biology, physiology and pathogenesis to accelerate the development of cell replacement therapies for endogenous epithelial cells that harbor disease-causing mutations, such as in BPD, cystic fibrosis or injured lungs.