Microscope view of the lungs
RESEARCH FEATURE

LungMAP: NHLBI project breathes life into first in-depth atlas of the human lung


Might pave the way for new and improved treatments for a wide variety of respiratory diseases

Maps may be great tools for helping you find your way around unfamiliar places, but in the future, a new type of map well might help save your life.

Welcome to the Molecular Atlas of Lung Development Program, or LungMAP, a historic effort to help researchers navigate the complex, poorly understood landscape of the human lung.  The project aims to create the world’s first comprehensive map of the dynamic molecular and cellular architecture of the developing lung. Researchers say a deeper understanding of these features could lead to better diagnoses and treatments for a variety of respiratory diseases, including asthma, COPD, cystic fibrosis, and bronchopulmonary dysplasia (BPD).

Funded by the National Heart, Lung, and Blood Institute (NHLBI), the project promises to “open the door to a new era in lung research,” says Sara Lin, Ph.D., program director of the Lung Development and Regenerative Biology Program at the NHLBI and LungMAP’s program officer.

LungMAP is basically an interactive, multifaceted web-based tool that provides researchers, educators, and clinicians a centralized way to collect, analyze, and visualize data about the structure and function of the myriad molecules, genes, cells, and tissues that make up the developing lung, including its hidden interconnections.

Human pediatric lung alveolar walls viewed under a high-powered microscope.
This image shows human pediatric lung alveolar walls (green-stained nuclei) draped over elastin fibers (gold), as seen through a multi-photon microscope. An individual alveolus, the gas-exchanging structure of the lung, is about the thickness of a sheet of paper. Source: Gloria Pryhuber, M.D., Cory Poole, University of Rochester Medical Center

Until LungMAP began in 2014, nobody had attempted to solve “one of the longstanding mysteries of medicine—how the smallest gas exchange units, or alveoli, form during development,” Lin says. The project hopes its discoveries will help reverse years of soaring U.S. respiratory disease-related death rates, led in large part by deaths from COPD.

“Although researchers have made great strides over the past three decades in treating lung diseases,” Lin says, “there is still a lot to be learned.” That’s why the project is working hard to generate, analyze, and map large amounts of high-resolution biomedical data through innovative and cutting-edge technologies. “We need to first understand the normal lung in order to better treat the abnormal lung,” she says.

The first phase of the project focused on lung development in both mice and humans, with special attention on understanding the developing lung from birth through early childhood. The second phase of the project will focus exclusively on the developing human lung and will extend the scope of the research into early adulthood (up to 25 years old, the age at which lung function typically peaks). It will also explore abnormal lung development in neonatal and pediatric rare diseases, with hopes of finding interventions that could help.

A key goal for many lung researchers: Figuring out how to coax endogenous stem cells, which can transform into virtually any cell type, to regenerate diseased or injured lung tissue. LungMAP augments the study of these stem cells and facilitates that process, which could help treat many types of lung diseases in the future, Lin says.

How the map will work

The LungMAP team includes researchers from universities, federal laboratories, and corporations who work through a nationwide consortium of four research centers, a data coordinating center, and a human tissue repository that collects and preserves human lungs, donated for research when not eligible for transplantation, for mapping. Information is shared with the wide community of lung researchers through a centralized website, www.LungMAP.net. As experimental data accumulates, the features of the website will expand.

Researchers will then have access to both data and tissue specimens from diseased and normal lungs so they can ask questions about them from the convenience of their computer screen, with options to input information and compare with their own data as well. These interactive features will allow identification of defective genes and disease biomarkers in order to find new diagnostic and therapeutic approaches faster and more efficiently than individual scientists working independently. LungMAP will also allow scientists to view 3D images of the lung and zoom in on structures of interest—even at the cellular level—to get a better understanding of how the lung works.

Jeffrey Whitsett, M.D., co-director of the Perinatal Institute at Cincinnati Children’s Hospital Medical Center and chair of the LungMAP Steering Committee, says the project has similarities to the widely-used Google Maps application. But instead of entering addresses into a search engine, researchers will provide “bioinformatics,” or biological data such as DNA sequences and proteins.

Screenshot of the homepage from www.LungMAP.net website
This screenshot shows the homepage from www.LungMAP.net. Source: LungMAP Team; NHLBI

“The power of LungMAP is really in this bioinformatics,” says Whitsett, who has studied lung disease for the past 40 years. “Researchers can insert complex biological data to understand structures, locations, cell types, what the cell is making, what the cell is doing, and how it interacts.” He says LungMAP also will help scientists to do research much faster than was possible even five years ago. “It’s a wonderful tool to study lung disease.”

Accomplishments

The project already is bearing fruit.  Researchers have produced nearly 100 research papers using LungMAP data. One study provided new insights into the how lung cells interact with the immune system. Another study provided new insights into how mammals adapt to breathing air after birth. 

Other notable accomplishments of LungMAP so far include:

  • Insights into the molecular and cellular interactions that result in alveologenesis, the complex process in which the lungs first develop their tiny balloon-like clusters of air sacs called alveoli 
  • First-of-its-kind single-cell transcriptomes and near single-cell proteomes of the developing lung, which involves examination of genes and proteins expressed at the level of individual cells
  • Identification of novel protein markers for the 40 known major lung cell types in humans
  • Development of a variety of tools for data annotation, integrated data analysis, and enhanced sharing with the research community
  • High-resolution 3D imaging of the structure of the alveoli – beyond the reach of computerized tomography (CT) or magnetic resonance imaging (MRI)
  • In vitro testing of isolated, purified, differentiated primary pediatric lung cells for responses to viral infections, oxygen, and e-cigarette vapors
     

As LungMAP enters its second phase, researchers say they are optimistic about its success in helping to understand the broad spectrum of lung diseases that affect millions of people worldwide. Many are hopeful that the powerful tool will take its place alongside other lung disease research tools now in use, including new imaging techniques, state-of-the-art genomics research, and well-designed clinical trials that have become a cornerstone of NHLBI’s research efforts. 

“LungMAP is a promising, cutting-edge project that could provide transformative research information for decades to come,” says James Kiley, Ph.D., director of NHLBI’s Division of Lung Diseases. “Fifty years from now, it’s conceivable that LungMAP will be remembered as one of the turning points in respiratory disease research.”

 

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