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Cancer Biology graduate program

Invasive cancer cells marked by distinctive mutations

What does it take to be a leader – of cancer cells?

Adam Marcus and colleagues at Winship Cancer Institute are back, with an analysis of mutations that drive metastatic behavior among groups of lung cancer cells. The findings were published this week on the cover of Journal of Cell Science, and suggest pharmacological strategies to intervene against or prevent metastasis.

Marcus and former graduate student Jessica Konen previously developed a technique for selectively labeling “leader” or “follower” lung cancer cells in culture, using lasers that turn a fluorescent protein from green to red. The leaders are more adventurous and invasive, but the followers support the leaders and help them survive. Check out our prize-winning video and their 2017 Nature Communications paper.

The magenta cells have leader-specific mutated Arp3 protein, while the green cells are unmodified followers.

The new research harnesses their technique to track the mutations that are specific to leader or follower cells. It was a collaboration with the lab of Paula Vertino, formerly at Winship and now at University of Rochester. Cancer Biology graduate students Elizabeth Zoeller and Brian Pedro led the work, with sophisticated genomics from Ben Barwick.

One of the leader-specific mutations was in Arp3, part of a protein complex that promotes the protrusion of cellular blobs, facilitating migration. The researchers took the mutated Arp3 protein from leader cells and forced its production in follower cells. In the cover image, the magenta cells on the outside are the ones with the mutated Arp3 protein, while the green cells are unmodified. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Lung cancer cells go amoeboid

Cancer biologists Jessica Konen and Scott Wilkinson, in Adam Marcus’ lab, recently published a paper on the function of LKB1, a gene that is often mutated in lung cancer cells. [Number three behind K-ras and p53.]

Amoeboid

Mesenchymal shape is defined as having a length more than twice the width. Amoeboid looks more like the cell on the right: rounded up. Thanks to Jessica Konen for photo.

Konen and Marcus were featured in a prize-winning video that our team produced last year, which discusses how they developed a technique for isolating “leader cells” — lung cancer cells that migrate and invade more quickly — from a large group and studying those cells’ properties more intensively.

The Molecular Biology of the Cell paper covers a related topic: how LKB1 mutation affects cell shape. In particular, losing LKB1 converts lung cancer cells from a “mesenchymal” morphology to an “amoeboid” morphology.  Read more

Posted on by Quinn Eastman in Cancer Leave a comment