Uncovering the secrets of the lungs, one cell at a time

In research, few institutions operate in a vacuum. Every cure, treatment, or breakthrough discovery relies on collecting and preserving samples, creating controlled experiments, and validating results—a process that requires close collaboration.

Golisano Children’s Hospital plays a key role in researching and understanding pediatric lung disease. As part of the LungMAP collective initiative, which is supported by the National Institutes of Health (NIH) to better understand healthy human lung development, GCH collects and preserves human lung samples provided by donors and then at the medical center These samples are distributed internally along with other facilities that study and map the entire lung down to a single cell.

In other words, the GCH has been the entry point for several major efforts to study lung disease and has developed a reputation for being very effective in this role.

“Our success lies in the fact that our preservation methods provide research-quality specimens to researchers across the country,” said Gloria Pryhuber, MD, professor of neonatology and director of the GCH LungMAP program. “Other institutions find that our tissue has unusual qualities, so they are able to use our resources to gain support for their projects, which allows them to further advance these single-cell technologies.”

GCH’s success has been recognized by multiple five-year NIH grants for its role in the LungMAP program. The current NIH Phase II grant (valued at $7 million) will soon end, and GCH will be the only institution eligible to submit a Phase III grant application because of its ability to maintain human tissue cores.

This effort extends beyond the lungs: GCH is also co-chair of HuBMAP, an initiative that takes the LungMAP model and applies it to all organs. “We can identify thousands of genes in each organ and how those genes are expressed in the cells,” Prihuber said. “We look at thousands of proteins in individual cells, and this research tells us how the cells function.”

The importance of the LungMAP and HuBMAP procedures is that researchers can map single cells using humans rather than animal models. “Until we truly understand human anatomy, we cannot confidently apply what we learn in laboratory models to humans because cells and structures are subtly but crucially different,” Prihuber said.

There are several components that are critical to making LungMAP work. First, GCH relies on the generosity of family members of deceased children to donate lung samples to the transplant network. Lung samples agreed for research but not eligible for transplant are then donated to GCH from the transplant center. Once arrived, each part of the organ is carefully cared for and preserved for advanced histology and model construction. Single cells can be cultured and therefore can be used as a model of human infection or chemical exposure.

The clinical impact of this network is substantial. Through the LungMAP collaboration, 70 to 80 cell types have been identified in the lungs, up from 40 previously thought. This enables caregivers to identify cell-specific causes of disease, including genetic mutations, and develop treatments to target them, which is a game-changer in the field of neonatology in particular.

“In the process, we have identified at least 10 genes in which disease-causing mutations have existed only in the past few years. In some cases, we realized we were able to predict the behavior of the mutations and treat them because we had identified Previously, newborns with these diseases required long-term intensive care treatment and may not survive. In many cases, we can now help more directly so that they can recover and go home,” said Pryhuber. .

It also aligns with developments in the field of genetics, where researchers can now use these cell maps to identify genes they were previously unable to identify. Because of these advances, researchers are discovering unique diseases, and although many of them are not yet treatable, this new knowledge could provide viable pathways to developing effective treatments.

“These studies will help us understand what happens if the lungs are damaged in order to heal and grow,” Prihuber said. “We could even seek to make progress in diseases like asthma, which are common conditions that we can control but don’t yet have a cure for.”

Recognition of leadership

GCH’s contributions to the LungMAP collective are recognized by the broader pediatric community: URMC was recently designated as a Designated Registry by the Pediatric Interstitial and Diffuse Lung Disease Research Network (chILDRN). The chILDRN National Registry was established in 2004 as a collection of academic medical centers that pool resources to advance knowledge about the etiology, phenotype, natural history, and treatment of rare lung diseases.

Currently, there are 25 active pediatric registration sites with more than 700 patients registered. URMC is the only medical center in upstate New York to receive this designation and the only hospital outside of New York City to receive this designation. URMC was selected as one of three new hospitals to join the registry by Children’s Hospital of Philadelphia (CHOP), a major children’s hospital. In addition to serving as a regional referral center for upstate New York, URMC is designated as a Pediatric Network Center for its ability to simulate lung anatomy through the LungMAP program and screen for rare genetic lung diseases through neonatal intensive care Diseases continue to grow in capacity. Pediatric Bone Marrow Transplant Program in the Nursing Unit (NICU) and Pediatric Hematology/Oncology.

“We have made significant progress in several key areas of lung development, but the LungMAP Biobank is an internationally recognized resource. By designating URMC as a site, the Children’s Registry will bring the knowledge and resources developed through the LungMAP program from Basic research moves to the clinical realm,” said Matthew McGraw, MD, assistant professor of pediatric pulmonology and principal investigator of the registry.

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 occur rarely, affecting one to four in 100,000 children, at least one to two cases are seen in our community each year. They are debilitating and often pose serious risks to a small group of children.

Additionally, “when you receive cancer chemotherapy or radiation therapy, you are at risk for serious infection of your lungs,” McGraw said. “This designation will help facilitate collaboration between pediatric pulmonology and hematology/oncology and will utilize pulmonary function laboratories to screen children receiving cancer treatment for the development of lung disease, particularly those at higher risk. Pediatric Bone Marrow Transplant Patients.” By screening for cancer treatment-related lung injury and identifying it early, interventions can be made to minimize the potential lifelong impact of this injury and improve the child’s quality of life.

The Children’s Network Center designation will also help GCH’s Neonatal Intensive Care Unit increase investment in genetic counseling and screening, which are critical for early detection of rare lung diseases.

“Clinical literature supports the need to screen children in the neonatal intensive care unit because most severe lung disease that meets childhood criteria and develops before the age of two has a genetic cause,” McGraw said. “Hopefully we can continue to introduce more More genetic counselors are available to support the group’s efforts.”

Being part of a national network facilitates communication and collaboration among experts in these diseases and accelerates the pace at which improved standards of care and novel and effective treatments are recognized, tested, and (where appropriate) implemented. Children’s Network designation and cross-network collaboration facilitated by the LungMAP program means improved, state-of-the-art care for children in the greater Rochester area.