For Christopher Vockley, a Duke University graduate student, the Lung Repair and Regeneration Consortium (LRRC) has been an opportunity to not only conduct important research but also to collaborate with and benefit from insights shared by some of the leading experts in his field.
Vockley is a student working with Tim Reddy, PhD, an assistant professor in Duke’s Department of Biostatistics and Bioinformatics, and Brigid Hogan, PhD, FRS, chair of the Department of Cell Biology. Hogan’s lab is one of the LRRC’s research centers, which investigate the mechanisms that control lung repair and regeneration. The research centers also develop new tools to facilitate research in lung regeneration, validate tools developed by other centers, develop collaborative research activities, support skills development, and host young investigators.
The research in Hogan’s lab is focused on the basic mechanisms underlying organogenesis and tissue regeneration, and how these processes involve stem and progenitor cells. Vockley and his colleagues in the lab study the development, maintenance, and repair of the trachea, airways, and lungs.
“My work is focused on understanding how the glucocorticoid receptor, a transcription factor necessary for lung development, works to turn on genes,” he said. “Mice that lack a functional copy of the gene that encodes this receptor die just after birth with underdeveloped lungs.”
The majority of Vockley’s work has relied on the utilization of novel genomic technologies, which he has designed and developed as part of his thesis research. In his investigation of the glucocorticoid receptor, he has leveraged the combined power of cell biology and integrative genomics research approaches.
This work, Vockley said, has implications for such conditions as chronic obstructive pulmonary disease and chronic asthma. Perhaps most importantly, it might provide insight into how to prevent the inadequate development of the lungs of very low-weight premature infants.
“Terminal lung morphogenesis is one of the last developmental stages a preterm baby must complete before they are able to survive in the outside world,” he said. “If a baby’s lungs have properly developed there is a much greater chance of survival in the case of preterm birth.”
Doctors can administer certain drugs to mothers who are about to give birth prematurely that turns on the glucocorticoid receptor, stimulating pulmonary surfactant production and speeding up the final stages of terminal lung morphogenesis. Understanding the basic biological mechanisms that govern the activity of the glucocorticoid receptor, Vockley said, will have implications for researchers’ understanding of both the normal developmental processes that rely on proper receptor function and the pharmacological activity of drugs that stimulate that function.
“There are a lot of things we don’t know, and there is still a lot to do,” he added.
In addition to his work on the glucocorticoid receptor, Vockley has participated in a trans-institutional collaboration involving other LRRC members in the Hogan lab at Duke and the Morrisey and Epstein labs at The University of Pennsylvania. Members of this collaboration are developing genome-editing-based protocols to knock out protein-coding and long non-coding RNA genes in primary human pulmonary cell types using CRISPR technology.
Vockley also said the LRRC has played a crucial role in advancing this research and aiding his professional development.
“The consortium has given me an opportunity, as a young researcher, to talk with people who are experts in these fields,” he said. “It’s been great to meet and interact with these people and hear about their work. That kind of experience is rare, and it shouldn’t be underestimated.”