Molecular Atlas of Lung Development

Under Construction: Molecular Atlas of Lung Development

November 3, 2014 at 12:11 am      

 

ATS members are beginning to map and annotate the 40-plus cell types in the normal developing lung as part of LungMAP, an ambitious program launched by the National Heart, Lung, and Blood Institute. The five-year, $30 million project involves 11 research centers and organizations, with expertise ranging from human tissue collection and molecular analysis to high-throughput assay development and bioinformatics.

Researchers taking part in LungMAP will assemble data from both the human lung—from the late canalicular to the alveolar stage (22-24 weeks in gestational age) to early childhood—and the mouse lung. As data is validated and added to the database, lung researchers will be encouraged to use the open resource to accelerate their own research and formulate new research projects.

“LungMAP is going to be a unique, high-impact program, which will use cutting-edge technology to generate and manage large amounts of high-quality data,” says James Kiley, PhD, director of NHLBI’s Division of Lung Diseases. “Through coordinated team efforts, these resources will be available quickly to serve the entire pulmonary research community.”

      James Kiley, PhD

A Resource for All Lung Researchers

The program is expected to be especially helpful to newer researchers, giving them a head start by providing an enormous amount of data that would take considerable time and resources to create while attempting to answer a specific research question.

For instance, through LungMap, a researcher interested in a certain gene will find the high-resolution expression pattern of that gene in both mouse and human lungs, the states of gene expression, in which cells the gene is co-expressed and with what other genes, and by which pathways the gene is regulated, according to Sara Lin, PhD, who serves as the program’s director at NHLBI.

Dr. Lin adds that another researcher studying a particular cell type will be able to go to LungMAP for a dataset about which genes are expressed in the cell type, how the expression profile changed during development, and how this cell type is related to other cell types in the lung.

        Sara Lin, PhD

LungMAP will also be useful to researchers interested in the broad range of lung diseases. Jeffrey A. Whitsett, MD, a principal investigator who is chief of neonatology, perinatal and pulmonary biology at the University of Cincinnati, notes: “Since tissue remodeling and loss of normal tissue architecture is at the core of the pathogenesis of all human lung diseases, the encyclopedic knowledge of the normal range of pulmonary cells and tissue behaviors will provide the basis to interrogate and understand the complex changes in cell differentiation and function associated with acute and chronic lung diseases that lead to the loss of alveolar structure and function.”

 

  Jeffrey A. Whitsett, MD

Murine Research and Other Benefits of LungMAP

Scott Palmer, MD, MHS, a principal investigator on the project who conducts murine research at Duke, believes having both the molecular atlas of normal human and mouse lung development will be highly beneficial to those researchers who study lung disease in mice. “The mouse model is a powerful tool, but there is a lot that is artificial and doesn’t translate as directly as we like in humans,” he explains. “With LungMAP researches will be better able to assess the relevance of their mouse models to human disease and, eventually, be able to create better models.”

In addition to this kind of data, researchers will be able to obtain human Scott Palmer, MD, MHS tissue samples and sorted cells, reagents such as antibodies

Scott Palmer, MD, MHS

and probes, protocols, and data analysis tools through LungMAP.

The NHLBI plans to launch tutorial and training sessions, both online at the LungMAP site and at major scientific meetings, including the ATS 2015 International Conference, which will take place May 15-20 in Denver.

“Our goal is to make the information and tools that come out of this project as useful as possible,” Dr. Lin says. “This is a very different kind of program. We don’t have a hypothesis or even a question, but if this program is done right and provides resources for all researchers, we will make a big impact for the whole lung field.”

ATS members and others can learn more about LungMAP by visiting lungmap.net. They may also provide comments and feedback through the website to Dr. Lin and the other leaders of the project.

Many Areas of Expertise Needed to Draw LungMAP
LungMAP will draw on the expertise of a wide range of medical centers, laboratories, and data centers. Below are the organizations leading the consortium, along with the principal investigators and the multiple principal investigators.

Research Centers
University of Alabama at Birmingham
Namasivayam Ambalavanan, MD (ATS member)

Yale School of Medicine
Naftali Kaminski, MD (ATS member)

University of California, San Diego-Rady’s Children Hospital-San Diego
James S. Hagood, MD (ATS member)

Pacific NW National Laboratory
Richard A. (Rick) Corley, PhD
Charles Ansong, PhD

Texas Advanced Computing Center
James Carson, PhD

Children’s Hospital Los Angeles University of Southern California
David Warburton, DSc, MD (ATS member)

Cincinnati Children’s Hospital Medical Center
Jeffrey A. Whitsett, MD

Children’s Hospital Medical Center
Steven Potter, PhD

Human Tissue Core
University of Rochester Medical Center
Gloria Pryhuber, MD (ATS member)

Administrative/Data Coordinating Centers
Duke University Medical Center
Scott Palmer, MD, MHS (ATS member)

RTI International
Robert F. Clark, PhD