Dow Lab

@dow_lab

Cancer genetics & biology lab, building and applying new genetic technologies in search of better treatment options for cancer patients

Vrijeme pridruživanja: ožujak 2018.

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  1. Prikvačeni tweet
    23. sij

    First for 2020! This has been a really cool study looking at response and resistance to inhibition in . It was a monumental effort, done almost single-handedly by Teng Han - not on Twitter - but looking for postdocs 👍. A thread 👇 /1

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  2. prije 18 sati

    Knowing how to use public transport ticket machines in a different city is so oddly satisfying.

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  3. 3. velj

    “We’re not in Kansas anymore, Toto” *checks notes* “Umm, actually, let me get back to you”

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  4. 2. velj
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  5. 31. sij

    How can “He did it... but we don’t care” be the conclusion to months of “He didn’t do it, this is a hoax”?? I just can’t with this BS anymore.

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  6. 28. sij

    Anyone want to guess at a *rough* estimate of how much has been spent on sequencing cancer genomes? Spoiler: I have NO idea...

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  7. 24. sij

    And after 5 years is on Twitter! Congrats, Teng!

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  8. proslijedio/la je Tweet
    24. sij
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  9. proslijedio/la je Tweet
    24. sij

    Great work from the !TGFbeta primes for Wnt independency in cancer 👇

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  10. proslijedio/la je Tweet
    23. sij
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  11. 23. sij

    That's it for now! Thanks to everyone in the lab, and all who contributed along the way! . Right, now I gotta go finish a grant! /Out

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  12. 23. sij

    Finally, though they are WNT independent the lineage reverted cells become entirely reliant on YAP/TAZ activity for survival -> treatment with either Verteporfin or genetic depletion completely shuts down proliferation, while WNT dependent cells are barely affected. /11

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  13. 23. sij

    In fact, in the absence of a SMAD4 mutation or TGFb priming, activated YAP (or TAZ) is sufficient to induce drug resistance. /10

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  14. 23. sij

    Turns out that TGFb priming engages YAP to rewire transcriptional programs and induce what we call ‘lineage reversion’, where the cells adopt a fetal-like state. Similar occurs during injury repair, as described by Stefano Piccolo and /9

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  15. 23. sij

    This was not an organoid culture artifact, as engraftment of TGFb-naïve cells led to escape from WNT suppression in vivo. However, like the in vitro cultures, those with disrupted TGFb receptor remained WNT dependent. /8

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  16. 23. sij

    To cut a very long story short, Teng figured out that not only was the genotype important, but to become resistant the cells had to be (transiently) exposed to TGFb. We dubbed this 'TGFb priming’. Cells with a dysfunctional TGFb receptor ('KRPT') never became resistant. /7

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  17. 23. sij

    About 25% of cases had downstream WNT reactivation, in some instances, by mutations or amplification of b-catenin... Not surprising. But the majority (75%) had no evidence of this. /6

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  18. 23. sij

    This is a relatively common genotype in CRC, so we needed to understand what was going on. What do you do when you don’t know what to do...? OMICS! All the omics! /5

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  19. 23. sij

    In most cases, these cells remained hyper-responsive to WNT974 (PORCN inhibitor), except for one genotype... those carrying KRAS (or BRAF), p53, and SMAD4 mutations. Unbelievably (to me at least 🤯), the same genotype could escape APC restoration! /4

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  20. 23. sij

    Taking a leaf out of the / Toshi Sato book, Teng engineered many, many primary organoid cultures to mimic the combination of oncogenic lesions seen in human RSPO fusion CRCs. /3

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  21. 23. sij

    A few years back, Teng built in vivo CRISPR-based models of RSPO fusions. He showed they were tumor-initiating events and extremely sensitive to PORCN inhibitors (that block WNT ligand secretion). Great! But these are not truly cancers... /2

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