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cellular research institute

cellular research institute

[ music ] >> most people don't die from aprimary tumor and actually now, for a lot of cancers, ifyou're able to diagnose it to a cancer very early on, you have a very goodchance of surviving. the problem arises when theprimary tumor metastasizes to further tissuesand that's when most of the survival ratesdecline dramatically. to be able to understandmigration,

i have to look at cells move. so a big way for meto do my research is to do live cell microscopywhere we have microscopes that allow us to actuallyvisualize the migration of cells live. you know we can seeexactly what's going on, how they migrate invarious environments. usually you can actuallyenvision that if you think about cell migration in thecontext of a normal response.

so if you think about whiteblood cells in your bloodstream which are called neutrophils. so these neutrophils areprobably the best cell -- the cells that migratethe best in your body. they are the fastest. they're very directional, andthey use a method of migration which is called amoeboid-typemigration. so meaning that they are ableto migrate and kind of walk as they are migrating or swim.

so they extend front feet, ifyou want, to kind of migrate and then they contracttheir backs. so they're kind ofwalking as they're going through the tissues, you know,to the site of infection. so let's say you cut yourself. they're going sense chemicalsthat are made at that site of inflammation there. and move very directionallyto that site to go in, and you know, eat up thebacteria or you know,

kind of calm downthat inflammation so that you can resume, youknow, a normal function. so what we learn in neutrophilsthen we try to apply it to metastatic cells andask when i look at them and they're migrating, cani think about what i know under normal conditions andsee maybe if i can apply it to a metastatic cellline, for instance. we've identified a breastcancer progression model where we can look at 4 celllines that come from being more

or less normal, youknow a mortal cell line. and that as stages, goto a metastatic stage. and we set out to visualize howthey look when they migrate, just their basicmigration phenotype, and we saw prettydramatic differences. you know that they endup, you know, becoming, you know they startbeing very organized in the very epithelial-liketissue and they migrate, you know, very nicely.

but as you progress throughthese 4 cell lines and you get to a metastatic state, now youstart to lose cell-cell contact. you have a very chaoticmovement. you start to have cells evendetach again migrating alone, which is what you probablywould expect in the context of what i've told you. so what we're doing nowis really understand, okay say now what happens fromthe normal cell to death cell. why is it that they nowbecome so erratic and chaotic

and you know, not reallybehaving very well? and then we start touse a lot of genetics, a lot of biochemistry. we actually visualizethe distribution of various components that regulate cellmigration using the green fluorescent protein. we end up working a lot withphysicists and mathematicians and engineers because allof this requires thinking

that goes beyond the biology. i need a number. i need to be able tolook at these movies and identify important metricsthat allow me then to compare and contrast various treatments,various genetic alterations that i can do withinthese cell lines. based on all thesethings together, by using the live imaging,by comparing the behavior of, you know, very lower eukaryotes

where they have migrationcharacteristics that are actually veryconserved into mammalian cells and we think even intometastasis in combination with the physicsand the engineering to get different surfaces forthem to migrate on and things like that, then we hopeto be able to gain insight into the very, verycomplex behaviors. [ silence ]

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