In the world of research, few institutions perform their work in a vacuum. Each cure, treatment, or breakthrough discovery relies on collecting and preserving samples, creating controlled experiments, and verifying results—a process that requires intensive collaboration.
When it comes to studying and understanding pediatric lung disease, Golisano Children’s Hospital plays a critical role in this process. As part of the LungMAP collective—a program supported by the National Institutes of Health (NIH) that was started to better understand healthy, human lung development—GCH collects and preserves donor-provided human lung samples, which are then distributed within the medical center and to other institutions, which study and map the entire lung up to single individual cells.
In other words, GCH has become the port-of-entry for several major efforts to study lung disease and has developed a reputation for being very effective in this role.
“We’ve been successful in that our preservation methods make research-quality specimens available to investigators across the country,” said Gloria Pryhuber, MD, professor in the Division of Neonatology and leader of GCH’s LungMAP program. “Other institutions have found our tissues to be of unusual quality, so they are able to get support for their projects using our resources, which allows them to further these single-cell technologies.”
GCH’s success has been recognized in the form of multiple five-year NIH grants for its role in the LungMAP program. The current phase-2 NIH grant—worth $7 million—will be winding down soon, and GCH will be the only institution eligible to submit a grant application for phase 3 due to its ability to maintain the human tissue core.
The effort goes beyond the lungs: GCH is also co-chair of HuBMAP, a program that takes the LungMAP model and applies it to all organs. “We can identify thousands of genes in every organ and how these are expressed in the cell,” said Pryhuber. “We look at thousands of proteins in individual cells, and this research tells us how cells function.”
The importance of both LungMAP and HuBMAP programs is that researchers can map individual cells using human, not animal, models. “Until we actually learn in the human anatomy, we can’t confidently apply what is learned in laboratory models to humans, since the cells and the structures are subtly but critically different,” said Pryhuber.
Several components are vital to the LungMAP effort. First, GCH relies on the generosity of families of deceased children to donate lung samples to the transplant network. Lung samples consented for research and that are not eligible for transplantation are then donated to GCH from transplant centers. As soon as they arrive, every portion of the organ is painstakingly cared for and preserved for advanced histology and model building. Individual cells are made available for culture so they can be used as a model of human infection or chemical exposure.
The clinical impact of this network is enormous. Through the LungMAP collaborative, 70 to 80 cell types have been identified in the lung, whereas previously there were thought to be only 40. This has allowed caregivers to pinpoint cell-specific causes of disease—including genetic mutations—and develop treatments for them, which has been a game-changer for the field of Neonatology, in particular.
“In this process we’ve identified at least 10 genes, just in the last several years, where there’s a mutation causing disease. In some cases, there’s a mutation that we realize we are able to predict the behavior of and treat because we have identified the gene. Previously, newborns with these diseases would need prolonged intensive-care treatment and might not survive. In many cases, we now can help more directly so that they can get better and go home,” said Pryhuber.
There’s also an alignment with the growth of the genetics field, in which researchers can now use these cell maps to identify genes that they couldn’t before. Thanks to these advances, researchers are discovering unique diseases, and even though many of them can’t yet be treated, this new knowledge could provide a viable pathway to developing effective treatments.
“These studies will help us understand what has to happen for a lung to heal and grow if it’s been damaged,” said Pryhuber. “We can even look to make progress on conditions like asthma, a common ailment which we can manage but not yet cure.”
A Recognition of Leadership
GCH’s contributions to the LungMAP collective have been recognized by the wider world of pediatrics: URMC has recently been named a designated registry center by the Children’s Interstitial and Diffuse Lung Disease Research Network (chILDRN). Established in 2004, the chILDRN national registry is a collection of academic medical centers that pool together resources to advance knowledge regarding the etiology, phenotype, natural history, and management of rare lung disorders.
Currently, there are 25 active chILD registry sites with more than 700 patients enrolled. URMC is the only medical center in Upstate New York—and the only hospital outside of New York City—to earn this designation. URMC was selected by Children’s Hospital of Philadelphia (CHOP), the lead chILD site, as one of three new sites to join the registry. In addition to serving as a regional referral center for Upstate New York, URMC was designated a chILD network center for its capacity to model lung anatomy through the LungMAP Program, as well as its growing capabilities to screen for rare genetic lung diseases through the neonatal intensive care unit (NICU) and the pediatric bone marrow transplant program in the Division of Pediatric Hematology/Oncology.
“We’ve made significant progress in several key areas of lung development, but the LungMAP biorepository is an internationally recognized resource. By designating URMC as a site, the chILD registry will translate the knowledge and resources developed through the LungMAP Program from foundational research to the clinical realm,” said Matthew McGraw, MD, assistant professor of Pediatric Pulmonology and registry site lead investigator.
LungMAP, along with GCH’s growing genetic-screening capabilities, provides the institution with advanced tools to identify and track rare lung diseases. While these types of lung diseases happen infrequently, affecting one to four in 100,000 children, at least one or two cases each year are found in our community. They are debilitating and often present serious risks for a sub-group of children.
In addition, “When you receive chemotherapy or radiation for cancer, your lungs are at risk for developing a bad infection,” said McGraw. “This designation will help boost collaboration between Pediatric Pulmonology and Hematology/Oncology and will utilize the pulmonary-function lab to screen children who undergo treatment for cancer for lung-disease development, particularly in pediatric bone marrow transplant patients who are at elevated risk.” Early recognition, by screening for lung injury related to cancer therapy, allows intervention to minimize the potential life-long effects of that injury and improve the quality of children’s lives.
The chILD Network Center designation will also help GCH’s NICU increase its investment in genetic counseling and screening, which is critical for identifying rare lung diseases at an early age.
“Clinical literature supports the necessity of screening for chILD in the NICU, as most severe lung diseases that both meet criteria for chILD and develop before the age of two have a genetic cause,” said McGraw. “Hopefully we can continue to bring in more genetic counselors to support the efforts of this group.”
Being part of a national network fosters communication and collaboration among experts on these diseases and accelerates the pace at which improved standards of care and novel effective treatments are recognized, tested and—where appropriate—implemented. This cross-network collaboration fostered by both the chILD Network designation and the LungMAP program means improved, state-of-the-art care for children in the greater Rochester area.