Radiation Resistance Kills: Can Zebrafish Help Us Prevent It?

When it comes to radiation therapy for cancer, cellular resistance to it can be a death sentence. What is the genetic basis for this resistance in humans? And what on earth do zebrafish have to do with it?

Well…a lot.

 Tune in to learn:

• Why it’s nearly impossible to conduct unbiased research on mice and other mammals
• How zebrafish are helping researchers overcome a major obstacle to cancer drug discovery  
• Why it may be more beneficial to focus on eliminating radiation resistance than on targeted therapeutics in cancer

When Samuel Sidi attended a French geneticist’s lecture in the early 90s, he had no idea the impact it would have on him and his career trajectory. The lecture was on a new zebrafish model, which would allow for the first time ever, unbiased forward genetic screening on a vertebrate.

Since vertebrates are more genetically and pathophysiologically similar to humans than the invertebrates commonly used for this research approach (e.g. Drosophila, worms, yeast), the zebrafish model opened the door to unprecedented and exciting opportunities in research—research that’s no longer limited by cost, time, and spatial constraints that previously existed for this approach in vertebrates.  

The zebrafish model also addresses a concern of Sidi’s and other researchers: invertebrates lack many pathways and mechanisms that are deregulated in disease, which means they are lacking as a research model for human disease.

Sidi is currently an associate professor at Icahn School of Medicine at Mount Sinai, where he's directing research in the Sidi Lab. Unique among other researchers in the zebrafish model world, he is applying the unbiased approach to cancer drug discovery research.

During his post-doc, Sidi developed a zebrafish model that models the problem of resistance to radiation therapy in human cancer. And recently, his MD/PhD student used this model to run an unbiased drug screen, which led to the identification of a compound that can restore radiation sensitivity in mutant zebrafish.

The result?

“Totally unexpected,” says Sidi.

Tune in for all the details.

Learn more at these links: 

https://labs.icahn.mssm.edu/sidilab/meet-the-team/ 

https://youtu.be/LnyxoxvtcPo

Episode also available on Apple Podcasts: apple.co/30PvU9C