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 likely 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 cell state.

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 non-tumor cell types, including fat, muscle, skin, and bone. It is not clear how tumor cells sense and signal to different cell types, nor is it known which biological pathways may regulate these interactions or how these interactions could promote tumor progression. In collaboration with Reuben Moncada and Itai Yanai (NYU), I applied spatially resolved transcriptomics and single-cell RNA-seq to a zebrafish model of melanoma to investigate how tumor cells sense and adapt to new cellular environments. Our work suggests that tumor and microenvironment cells at the invasive front of the tumor together upregulate a common set of cilia genes, which may be important in tumor growth and invasion.

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 also 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.