Mou Laboratory: Hongmei Mou, PhD

Overview

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 at Massachusetts General Hospital 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.

Research Projects

Stem cells and human airway disease studies: Generating unlimited and functional patient-specific and disease-specific airway epithelium

Currently one major technical bottleneck in developing personalized therapies for airway diseases such as cystic fibrosis (CF) is the inability to procure a large number of functional airway epithelial cells. Since stem cells can self-renew and to give rise to multiple types of differentiated cells, they can contribute to developing personalized therapies.

In principle two unlimited populations of airway stem cells can be generated in a patient-specific manner. The first cell population consists of adult airway stem cells in which endogenous stem cells are isolated and expanded indefinitely. The second cell population is derived from patient-specific induced pluripotent stem cells (iPSCs) that efficiently differentiate induced cells into adult-like airway stem or progenitor cells.

Dr. Mou’s laboratory is focused on the generation of unlimited cells, from primary airway stem cells or iPSCs, with an ensured differentiation capacity. These cells are a resource for disease modeling, drug screening (personalized medicine), and repopulating damaged tissues (cell therapy).

Modeling of molecular regulators in human lung development and defects

Neonatal lung defects are a major cause of early mortality and long-term disability in infants. A better understanding of the cellular and molecular basis of normal human pulmonary development will help define the mechanisms that cause abnormal development of the embryonic lung resulting in a birth defect.

Specifically, our lab is interested in the study of the cellular and molecular mechanisms underlying human fetal airway and lung progenitor cell specification, determination, plasticity and related pathogenesis, such as congenital and neonatal abnormalities in the lung.

Collaborators:

Bryan P. Hurley, PhD, Assistant Professor of Pediatrics, Harvard Medical School

Martin Mense, PhD, Vice President, Drug Discovery, Cystic Fibrosis Foundation Therapeutics

Steven Rowe, MD, MSPH, Nancy R. and Eugene C. Gwaltney Family Endowed Chair in Medical Research and Director, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama, Birmingham

Paul Lerou, MD, Chief, Neonatology and Newborn Medicine, Mass General for Children

Jayaraj Rajagopal, MD, Principal Investigator, Center for Regenerative Medicine and Physician, Pulmonary and Critical Care Unit

Our Team

Principal Investigator

Hongmei Mou, PhD
Assistant Investigator, Mucosal Immunology and Biology Research Center,
Massachusetts General Hospital
Research Staff, Pediatrics, Massachusetts General Hospital
Assistant Professor of Pediatrics, Harvard Medical School

Research Team

Michael Wood, Research Technician

Publications

Full list of publications