Confined melanoma cells protect their nuclei from mechanical stress.
Mechanical regulation of cancer cell biology
Tumors grow within a confined space - the human body. A rapidly growing tumor exerts a significant degree of mechanical force on surrounding tissues. Neighboring tissues also exert force on the tumor that could act to restrain tumor growth. I am currently studying how growth of tumor cells within confined spaces influences their biology and behavior. Using human cell lines and a zebrafish model of melanoma, I am applying cutting-edge imaging and bioinformatics approaches to characterize the effect of confinement on melanoma plasticity and tumor progression.
Relevant publications:
Hunter et al., bioRxiv (2024) link
Cilia (yellow) extending between the tumor (magenta) and neighbouring muscle.
Spatially resolved transcriptomics of the tumor-microenvironment interface
As tumors grow and invade into new tissues, they come into contact with many new cell types. It is not clear how tumor cells sense and signal to different cell types, which biological pathways regulate these interactions, or how these interactions promote tumor progression. To investigate this, I applied spatial transcriptomics and single-cell RNA-seq to a zebrafish model of melanoma. I found that cells spanning the tumor boundary undergo significant transcriptional reprogramming adopting a novel “interface” cell state. This finding, one of the first to apply spatial transcriptomics to cancer, demonstrates that there is bidirectional signaling between tumors and healthy tissues that enables cancer invasion, identifies numerous targets to block cancer progression, and validates the importance of spatial context in interpreting tumor cell behavior.
Relevant publications:
Hunter, Moncada, et al., Nature Communications (2021) link
Zhang et al., Cell Systems (2023) link
Baron et al., Cell Systems (2020) link
Previous work (Ph.D research):
Essential roles for endocytosis and oxidative stress in mediating cell polarity during embryonic wound healing
During my Ph.D, I explored the striking ability of embryos to heal wounds rapidly and without scarring. I used quantitative confocal microscopy to discover an essential role for endocytosis in directing redistribution of junctional and cytoskeletal proteins around wounds in Drosophila embryos. I then investigated the upstream signals that promote polarized trafficking around the wound, and discovered a conserved, essential role for oxidative stress in promoting wound closure. I found that reactive oxygen species (ROS) are released by the mitochondria of wounded cells in both fly and zebrafish embryos, and signal to the surrounding cells to polarize junctions and the cytoskeleton to promote healing.
Relevant publications:
Hunter et al., Developmental Cell (2018) link
Hunter et al., Journal of Cell Biology (2015) link
A large wound in the epidermis of a Drosophila embryo.