Pulmonary Medicine
Brewington Lab

Dedicated to Helping Children with Cystic Fibrosis

Pulmonary diseases in children take many forms, from genetic or congenital changes to acquired pathogens, but almost all impact the lining of the respiratory tract in some way. This respiratory epithelium, from our nose to our alveoli, interacts with the outside world breath-to-breath, and small alterations in this tissue can create significant pathology.

The Brewington lab works to further understand respiratory diseases through the lens of the epithelium, with a specific focus on cystic fibrosis, or CF. We employ several model systems, most derived directly from human tissues, to study these diseases and better understand the pathogenesis and treatment of respiratory illness.

Improving Care Models Through Research

In CF specifically, our lab seeks to improve personalized, precision care models in the clinic through translational research. CF is caused by mutations in the CFTR gene, with over 2,000 such mutations described to date. It is estimated that half of these variants occur in 5 people or less across the world. Each mutation causes different changes in the CFTR protein, meaning different tools are needed to fix this protein dysfunction. Some of these tools, called CFTR modulators, are available for people with certain more common CFTR gene mutations, but not to those with rare variants. Our lab seeks to identify people with rare CFTR genotypes that would benefit from these therapies but do not otherwise have access to the drugs because of the rarity of their CFTR mutations.

Using patient-derived epithelial models from nasal cell brushings, we can quantify an individuals’ baseline level of CFTR protein function and use the same models as a testing ground for patient-specific treatments. Through this approach, we seek to match the right patient to the right drug, even (and especially) for individuals who do not have access to such treatments but may have biologic benefit. We also are working to identify patient- and therapy-specific factors that might impair the impact of these therapies, to understand the molecular factors that contribute to patient-patient variability in disease severity and drug response, and to aid in the development of novel treatments for CF.

In addition to our work in CF, we collaborate on numerous projects ranging from congenital airway malformations, primary lung cancer, understanding the immunology of the lung, and more. Our lab also operates a large respiratory biorepository, including thousands of banked bronchoalveolar lavage samples and more.

Bringing Personalization to the Forefront

The CF community is on the front lines of a push for more personalized clinical care with the advent of CFTR modulators. There are significant gaps in the execution of this care model, however, that our lab works to address.

  • CFTR modulator drugs are disproportionately available to individuals with more common CFTR genotypes. This in turn means that more Caucasians with CF have access to modulators compared to minority populations.
  • As more modulator drugs enter the market, many individuals may have access to more than one treatment, without clear guidance on how to select the right treatment.
  • Disease variability in CF remains poorly understood, with at least 50% of the patient-patient variance due to factors outside of the CFTR gene; this variability continues in the post-modulator era.

To maximize the potential of our available treatments and close these gaps, high-fidelity models of disease are needed both to understand the cellular and molecular drivers of these issues, as well as to derive optimal treatment regimens for individual subjects. Our work has already created pathways to CFTR modulator access for numerous individuals that otherwise would not be taking these treatments, leading to direct clinical benefit. We hope that through these lines of research we can move towards a model that provides both equitable and precise care for all.

About the PI

A photo of John Brewington.

John Brewington, MD

My research goal is to provide personalized, precise care to patients with rare CF genetic variants. I specifically work with patient-derived models of respiratory epithelia to model different functions of the CF airway. Through this work, I seek to maximize the potential benefits of CFTR modulator drugs by expanding access and aiding in clinical therapeutic selection.

Learn More and Meet My Team