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Rac-enhanced CAR immunotherapy: RaceCAR

Published on January 30, 2025   51 min

Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms

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0:00
Hi. My name is Denise Montell, I'm a professor of molecular, cellular, and developmental biology at the University of California in Santa Barbara. I'm going to tell you today about a project that really started out as fundamental basic cell biology in the fruit fly ovary and it took us entirely unexpectedly into a potential clinical application specifically an enhanced cellular immunotherapy.
0:28
My lab is generally interested in how cells behave normally as they're building and maintaining tissues and then how they misbehave in diseases like cancer. A dream for us would be to be able to harness this knowledge to treat disease. For many of our studies, we use the model shown here the drosophila ovary because of the rich diversity of biological questions that can be addressed by the simple and beautiful anatomy of this tissue, the powerful experimental tools available in this organism and, of course, the long history of success using drosophila to solve fundamental problems in biology. Now, the ovary as you see here is composed of individual strands of developing egg timbers. At the tip of each one of these strands reside stem cells, two different kinds of stem cells, somatic stem cells and germline stem cells. And the progeny of those cells assemble into these little ovals called egg chambers and each egg chamber grows and develops into a mature egg, which you can see near the center of this flower-like structure.
1:37
Now if we zoom in on one of those strands of developing egg chambers, the stem cells as labeled here are up near the anterior tip of this structure. Then the developing egg chambers are arrayed in a sort of assembly line fashion in increasing size as they grow and mature. We can see the detailed anatomy of an egg chamber here where in the center of the structure are 16 cells that are germ cells. One cell the oocyte is the cell that's going to grow into the egg itself. Connected to it are these giant cells the nuclei are labeled in blue here called nurse cells. And the nurse cells' job is to nourish the oocytes by providing it with the cytoplasm. Surrounding the nurse cells and oocytes are the somatic cells. And we can see that most of them stack up in a columnar layer in contact with the oocyte. Leaving a few cells to spread out in this thin squamous layer around covering the nurse cells. Now a group of cells that my lab has been interested in for some time starts out as part of this epithelium when all the cells are more or less the same cuboidal shape. But then as the reorganization occurs where most of the cells are stacking up in a columnar epithelium and some of them are stretching out into this thin squamous layer, the border cells actually detach from the epithelium entirely and migrate in between the nurse cells. They squeeze in between the nurse cells until they reach the anterior border of the oocyte, which is why they were named border cells.

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