For years, researchers at the University of Rochester Medical Center (URMC) have been studying the fundamental processes in human lung growth and maturation as part of the NIH-sponsored Lung Development Molecular Atlas Program (LungMAP) and the Human BioMolecular Atlas Program (HuBMAP) collaboratives. These efforts include many URMC researchers and has been led by Gloria Pryhuber, M.D., professor in the Department of Pediatrics at URMC.
Now, with the onset of COVID-19, these efforts continue to provide an even more invaluable resource, as the LungMAP and HuBMAP programs pivot to study the effects of the COVID-19 virus on the human lung. The LungMAP program was recently awarded $1.36 million from the National Heart Lung and Blood Institute (NHLBI) to provide, by mass cytometry, RNA sequencing and in vitro primary cell culture models, single cell level transcriptomic and protein analyses of parenchymal and resident immune cells in pediatric (1d- 21y) as compared to adult (22-60+y) human lungs with and without COVID-19 infection.
Pryhuber’s lab has already been providing data on lung development and will provide unique cells and tissues for the study of COVID-19 lung injury. This new funding will help understand COVID’s effects on children’s lungs.
“Our program is unique in our ability to study human lung, while most programs study mice or other models,” said Pryhuber, “The LungMAP and HuBMAP programs are creating an atlas of the lung, mapping the organ down to each single cell. At URMC, our strength is uniquely focused on studying the lung at the single cell level in the pediatric age range, when so much lung growth is happening while the chance of lung injury by infection, asthma and the environment is also high.”
For Pryhuber, the focus of this COVID research will be to examine why children get the infection at a lower rate and remain more asymptomatic than the older population. One of Pryhuber’s hypothesis –gathered from examining existing datasets - is that children don’t have as high an expression of the proteins and co-receptors that allow the virus to get into the lung cells.
“For the virus to cause infection there has to be viral entry and replication machinery. We will continue to utilize our samples and datasets to identify what cells in the airway and lung express potential receptor and co-receptors. There is evidence that environmental exposures that come with age may enhance this machinery. With our data, we will try to understand what influences co-receptors in adults as opposed to children.”
In addition to studying the expression of these viral entry proteins in human lung samples, Pryhuber and her team will be looking at differences in the inflammatory response between adults and children.
“With COVID, the concern is not so much the presence of infection, but the body’s response to infection. Humans try to get rid of the virus, but in the process we injure ourselves with the inflammation. We’re studying how children clear the virus with less inflammation, with the goal to seeing if we can modify the adult inflammatory response to get the same results.
Pryhuber’s research program has received national recognition for its unique and innovative abilities to study fundamental processes in human lung growth and maturation. Her lab created the BioRepository for Investigation of Diseases of the Lung (BRINDL) which now contains more than 280 human lung sets, with a subset that are normal by history and histopathology and more than 120 with a specified disease, spanning premature infants to adults. Working with the United States Organ Procurement and Transplantation Network (OPTN), the lab accepts donated organs when they cannot be placed for transplantation, and respectfully preserves and distributes lung to support molecular, temporal and spatial characterization of functionally and anatomically defined cell types. The work highlights the importance of the United States Transplantation Network and Donor Gifts for Research that goes well beyond organ transplantation. Where one donor can save 8 recipients with transplanted organs, organ donation for research will reach 100s to 1000s of people as new diagnoses and treatments are discovered.