Value Proposition
· Permanently labels cells that have experienced hypoxia, enabling long-term tracking
· Captures tumor evolution by identifying cells with past hypoxia exposure, not just at the time of tissue collection
· Enables investigation of metastasis by tracking cells from hypoxic niches that may retain aggressive phenotypes
· Supports development of therapies targeting hypoxia-adapted, reactive oxygen species-resistant cancer cells
· Compatible with both cell lines and transgenic animal models
· Applicable to a wide range of disease models including cardiovascular disease and ischemia
Unmet Need
· Metastasis is the leading cause of cancer mortality, thus, pinpointing and reducing causes of tumor metastasis can lead to more effective cancer therapies.
· Hypoxia is known to drive aggressive cell behavior, but since hypoxia is a dynamic environmental condition for cells, it is difficult to track.
· Existing tools only capture real-time hypoxia, leaving a gap in tracking cells with prior exposure and high metastatic potential.
· Therefore, there is a strong need for a method to reliably track hypoxic cells, and more generally, a need for more biomarkers for high metastasis-risk cells.
Technology Description
· Researchers at Johns Hopkins have developed a hypoxia fate-mapping system, which permanently labels any cell that has undergone a severely hypoxic state.
· This mapping system uses a fluorescent marker that changes from red to green fluorescence when the cell is hypoxic, and this change is irreversible. This enables researchers to track the post-hypoxic tumor cells over time, monitoring their migration, survival, and colonization.
· This mapping system was verified in both in vitro and animal models.
Stage of Development
· Validated in both in vitro and in vivo models:
o In vitro studies utilized breast cancer cell lines
o In vivo studies performed in mouse models
· These findings support the technology’s readiness for expanded preclinical studies, including broader disease models and therapeutic targeting strategies.
Data Availability
· The RNA-sequencing data have been deposited in the GEO database under the following codes:
o GSE111653 (in vitro hypoxia)
o GSE126609 (tumor)
o GSE136372 (lung)
· Additional data available upon request.
Publication
· Godet, I., Shin, Y. J., Ju, J. A., Ye, I. C., Wang, G., & Gilkes, D. M. (2019). Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis. Nature communications, 10(1), 4862. https://doi.org/10.1038/s41467-019-12412-1
