Cracking the Code

Le Bonheur and University of Tennessee (UT) Health Science Center physicians Jonathan D. Finder, MD, and Terri Finkel, MD, PhD, were recently named co-principal investigators of a five-year multicenter National Institutes of Health research project (R01) grant, “Integrative Genomics of Childhood Interstitial Lung Disease.” The grant uses genetic data from Le Bonheur and the UT Health Science Center’s Biorepository and Integrative Genomics (BIG) Initiative to better diagnose patients with childhood interstitial and diffuse lung diseases and determine genetic causes of the disease. Finder serves as a pediatric pulmonologist at Le Bonheur and professor of Pediatrics at UT Health Science Center, and Finkel serves as interim chair of Pediatrics at Le Bonheur and UT Health Science Center.

Terri Finkel, MD, PhD, interim chair of Pediatrics, is one of two investigators at Le Bonheur participating in a study to help determine the genetic causes of childhood interstitial lung disease. Researchers hope this work will lay the foundation for future treatments and faster diagnosis.

“This is another piece of our effort to identify the causes and treatments for critical illness in our children,” said Finkel. “A lot of our efforts are still trial and error to get to the diagnosis of interstitial lung disease, a rare disease. With this study, we hope we can take away that trial and error and use what we know from data about the genetic code to provide earlier diagnosis and treatment.”

Childhood interstitial lung disease (chILD) is a group of conditions that impact the lung tissues of infants and children. This project, led by investigators at Boston Children’s Hospital and Harvard University, has the aim of using several methods to define the genetic landscape of chILD. Investigators will analyze lung biopsy samples of patients with chILD to define molecular profiles of the disease and their clinical significance, and DNA sequencing of patients with chILD will seek to identify new causative genes for the condition.

Le Bonheur and UT Health Science Center will be involved as part of the Genomics Information Commons (GIC) – a genetic database from eight pediatric centers around the country that includes genetic data from the Le Bonheur and UT Health Science Center BIG Initiative. As a part of this grant, patients in Le Bonheur’s DNA repository database who are identified as having suspected genetic markers for chILD will be sent to Finder’s clinic for a standardized, in-depth analysis of this illness. This data will allow researchers to better understand how the same disease may present in different children.

Patients identified in Le Bonheur and UT Health Science Center’s DNA biorepository to have suspected genetic markers of interstitial lung disease will be seen by Le Bonheur Pulmonologist Jonathan Finder, MD (above left) for a standardized analysis of the presentation of the disease.

“This is a completely new way of thinking about human disease,” says Finder. “We’re going from the DNA to the person – exactly the opposite of how we have typically done this. It’s an exciting way of approaching disease, especially for a rare disease that can have a missed diagnosis.”

This work will help define the genetic landscape of chILD and assess the patterns that the disease follows, says Finkel. The hope is that it will lay the groundwork to better understand the disease and how children with chILD present and progress so that future treatments can be better measured. The genetic causes that are identified from this study could inform the development of more specific therapies and better care for children with this disease.

“Through this study, we are trying to assess the patterns of disease so that once we know the genetics and the cure or treatment has been developed, we can determine if we are helping or hurting with that treatment,” says Finkel. “It’s also the ‘why.’ Why do my patients have these diseases, what triggered this and why them and not their sibling or classmate?”

“The utility of large whole genome sequencing like this means earlier identification of significant lung disease,” says Finder. “It completely upends the way we approach disease and patient care.”