Job Description
Ephrin/Eph signaling in lung development and regeneration: Postdoctoral project
Interactions between epithelial and endothelial cells in the lung alveolus are required to establish the gas exchange interface and mediate the critical function of the lung: transfer of oxygen and carbon dioxide between the body and the external environment. Incomplete lung development, acute or chronic respiratory diseases, and lung cancer disrupt this interface and are leading causes of death worldwide. A recent longitudinal analysis of the regenerative response of the lung alveolus to influenza infection has demonstrated that the cellular compartments of the lung respond differently to injury and that the timing and extent of cellular interactions across the alveolus likely determine the success or failure of regeneration.
Large genomic datasets have revolutionized our approach to studying complex tissues; however, it is essential to expand studies of novel cell states to determine how cells interact with one another to direct tissue morphogenesis. Mapping communication between cellular compartments in the alveolus during regeneration using CellChat has identified a potential role for endothelial-epithelial ephrin/Eph signaling in lung repair. Ephrin/Eph signaling often requires cell-cell contact, and signaling downstream of Ephs and ephrins is known to modulate cell self-organization and tissue morphogenesis in multiple contexts. Because communication and interaction between the lung epithelium and endothelium is required to reestablish the gas exchange interface after injury and restore lung function, ephrin/Eph signaling may play an essential role in cell-cell communication leading to repair of lung tissue structure.
Thus, a postdoctoral fellow position is available for a very interesting collaborative study that will dovetail the Daar laboratory interests with the laboratory of Dr. Terren Niethamer. The successful candidate for this position will integrate analysis of genomic datasets with studies of ephrin/Eph signaling and morphogenesis in both in vivo (model organism) and ex vivo (cell culture) systems. This project will provide insight into the role of endothelial Eph/ephrin signaling in lung development and regeneration and determine how endothelial cells interact with their niche to form 3D structures necessary for organ development, function, and repair. In addition, the established role of ephrin/Eph signaling in cancer progression and the emerging role for endothelial cell signaling in metastasis indicate that these mechanisms may be co-opted by cancer cells to drive tumor progression.
- Analysis of scRNA-seq data to identify the timing of expression and level of expression of Eph/ephrin pathway members in lung cells during regeneration following influenza infection
- In vivo validation of ephrin/Eph pathway member expression using immunofluorescence and/or RNAscope in mouse and human tissue sections
- Inhibition of ephrin/Eph signaling in an ex vivo alveolar organoid system or cultured precision-cut lung slices
- Inhibiiton of ephrin/Eph signaling using mouse genetic knockout experiments during postnatal alveologenesis, adult homeostasis, and regeneration following influenza infection
Overall goal: Determine whether loss of identified Eph/ephrin signaling pathway members results in changes to alveologenesis or regeneration following influenza infection, with a particular focus on changes to alveolar structure and cell behavior.
Qualifications and Job Details
Required and Preferred Skills
A strong background in molecular, cellular, or developmental biology is required. Interested candidates should have a Ph.D. and/or an M.D. and have less than 5 years postdoctoral experience.
About the NCI Center for Cancer Research
The Center for Cancer Research (CCR) is home to nearly 250 basic and clinical research groups located on two campuses just outside of Washington, D.C. CCR is part of the National Cancer Institute (NCI) and makes up the largest component of the research effort at the National Institutes of Health (NIH). Centrally supported by long-term funding and a culture of complete intellectual freedom, CCR scientists are able to pursue the most important and challenging problems in cancer research. We collaborate with academic and commercial partners and advocacy groups across the world in efforts to prevent, diagnose and treat cancer and HIV/AIDS. The CCR research portfolio covers the full spectrum of biological and biomedical research. Our work ranges from basic to translational and clinical, and our clinical trials are conducted in the NIH Clinical Center, the world’s largest hospital dedicated to clinical research that offers a robust infrastructure to support CCR’s patients on an estimated 250 open studies. The success of CCR is grounded in an exceptionally strong discovery research program that provides the foundation for the seamless translation of insights from bench to bedside. Read more about CCR, the benefits of working at CCR and hear from our staff on their CCR experiences.
Frederick
Frederick is the second largest city in Maryland but retains a “small town” feel, surrounded by mountain views with a vibrant Main Street community. The city offers outstanding schools, a balanced and thriving economy and a highly educated workforce.
Our laboratory is located at the NCI-Frederick campus and offers state-of-the-art facilities in an exciting environment for postdoctoral research. The NCI offers competitive postdoctoral stipends. Qualifying fellows from abroad will be provided a J-1 Visa.