Studying how the actions of single cells act to drive disease

The Headley Lab is particularly interested in the cellular dynamics underlying the spread of tumor cells from primary cancers of the skin and breast to the lung, in a process called lung metastasis.  For most cancer patients metastasis is the leading cause of death. In cancers such as breast cancer and melanoma, the primary tumor can certainly cause tremendous pain and even disfigurement, however it is the strong tendency for these cancers to spread to the lung, liver, or bone that impairs critical life supporting function and leads to death.

Metastasis by its very nature is an incredibly dynamic process where individual cellular interactions have significant importance. Metastatic spread is usually thought of in a series of discrete steps leading from initial escape from the primary tumor into the bloodstream and subsequent transit and entry into distant organs like the lung. Each of these steps is characterized by the pressures faced by the cells at each stage, determining whether they live-on or die-off. Importantly, a variety of studies have shown that most metastases originate from individual cells or at most small clusters of cells as opposed to large populations. Thus, to truly understand this process we need to define the events at the single cell level which influence the eventual fate of that prospective metastatic cell.

Avoiding attack by the immune system is considered one of the most prominent pressures faced by metastatic cells at all stages. We have recently developed a method to observe the real-time behaviors of immune cells and tumor cells in the lungs of live mice at very high resolutions for the first time. This method has allowed us to literally open a window on the process of lung metastasis in order to understand how immune cells interact with and change the fate of tumor cells trying to setup a new home in the lung. We are combining analysis with this approach with other cutting-edge techniques such as single cell RNAseq, allowing us to not only understand the behaviors of these critical cells but also the molecular switches that drive these metastasis influencing functions.

This movie shows the dynamic nature of a metastatic tumor cell in vivo in the lung of a mouse over 9 hours. The tumor cell is displayed in green and the surrounding lung tissue in blue. Credit: Headley et al. Nature 2016
This movie shows a lung dendritic cells in red engaged in an intimate interaction with a tumor cell (green) in the lung. Tumor material that has been ingested by this cell can be clearly seen contained within the dendritic cell. Credit: Mark Headley 2016 (unpublished data)
This movie shows a tumor cell just having entered the lung vasculature and then dying moments later. The tumor cell is displayed in green and its nucleus in blue. The surrounding lung tissue is highlighted in red and vascular flow in teal. Credit: Headley et al. Nature 2016