Terren K. Niethamer, PhD

I am a cell and developmental biologist fascinated by endothelial cells, which line blood vessels in the lung. The goal of my research program is to understand how endothelial cells communicate with other lung cells to build complex three-dimensional structures during development and regeneration. Answering this question will help us determine how tissue structures are built and rebuilt and how this process can go wrong in the diseased or injured lung.

My original inspiration to study endothelial cells came from my interest in lung alveolar structure and its connection to function. I am fascinated by the beautiful three-dimensional structure of the gas exchange interface in the lung, in which the large, flat alveolar type 1 epithelial cell overlays the capillary network lined with endothelium. How do endothelial cells contribute to development and regeneration of this complex structure? This question is essential to the pursuit of improved regenerative therapies for patients with lung disease.

Single-cell genomics has revolutionized our understanding of the heterogeneity of lung cell types during development, maintenance of homeostasis and disease. These experiments have identified novel cell types and provided great insight into the mechanisms of lung repair. In addition, analysis of the epigenome using the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and single-cell ATAC-seq have provided unprecedented opportunities to understand the factors that define cell fates at the single-cell level. To develop much-needed regenerative therapies in the lung, however, it will be essential to understand not only how cell fates are defined, but also how three-dimensional tissue architecture is formed.

My research program integrates genomic techniques, ex vivo approaches in mouse and human primary cells and tissue, and mouse genetics to develop a fundamental understanding of how endothelial cells communicate with other cell types in the lung alveolar niche to drive development, maintain homeostasis and effect repair after injury. I am particularly interested in the role of endothelial signaling in tissue morphogenesis. Our work will improve understanding of mechanisms of cellular self-organization and tissue morphogenesis in lung development and regeneration by:

• Expanding our knowledge of how lung endothelial cell fates are established and maintained
• Determining how endothelial cell signaling affects alveolar development and repair
• Defining the impact of endothelial cell signaling on alveolar tissue organization

The long-term goal of my group is to benefit lung and vascular biology, as well as society, by using the scientific knowledge we gain to improve therapies for human lung and vascular disease.