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Rob Manguso @MangusoLab

Official twitter of the Manguso Lab @MGHCancerCenter @BroadInstitute @harvardmed, studying cancer immunology using functional genomics and systems immunology

Joined June 2019
  • Tweets 220
  • Following 1,126
  • Followers 1,397
93 Photos and videos
Excited to share out latest work, out this week in @NatureGenet . In this study, we using CRISPR screens to explore how sensing inflammatory cytokines exposes new tumor-intrinsic dependencies. @broadinstitute @MGBResearchNews nature.com/articles/s41588-0…

Inflammatory cytokines induce new cancer dependencies

Nature Genetics - Cheruiyot et al. conduct genome-scale in vitro CRISPR loss-of-function screens to map genetic vulnerabilities induced by inflammatory cytokines and identify the...

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We also find an IFNg-specific dependency for loss of the lipid phosphatase FITM2, previously observed by Lawson et al (nature.com/articles/s41586-0…). We found that deletion of this gene in tumors causes a dramatic sensitivity to immunotherapy in pancreatic and renal cancer models.
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Much more great screening and mechanistic work in the manuscript. A tour de force by Collins Cheruiyot, a former HMS PhD student in my lab. Congratulations to Collins, Sarah Kim, @kathleenbyates , and all our co-authors and collaborators that made this work possible!
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Our latest work on IO target discovery is out this week. Amazing collaboration with @DrUppaluri and led by Cong Fu. We performed in vivo CRISPR screens in #HNSCC to identify targets to enhance ICB response. @MGHCancerCenter @broadinstitute @DanaFarber nature.com/articles/s41467-0…

In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target

Nature Communications - UCHL5 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains. Here, the authors discover through in-vivo CRISPR-Cas9 screens that Uchl5 is involved in...

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Interestingly, we find that deletion of Col17a1 alone (just 1 gene regulated by UCHL5) does enhance ICB response, although not to the same degree. Further, Col17a1 overexpression can reverse the ICB sensitivity seen in UCHL5 KO tumors.
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Overall, we help inform the development of new immune-based therapies targeting HNSCC. At the advanced stage this is a deadly cancer that is poorly responsive to current immunotherapy approaches.
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Rob Manguso retweeted
Ravi Uppaluri, MDPhD@DrUppaluri
30 Sep 2025
Congrats to DrCongFu ! Wonderful to collaborate with @MangusoLab on in vivo CRISPR of epigenetic targets study in #HNSCC models @NatureComms @kathleenbyates @IOTNmoonshot Thanks also to @SilvioGutkind @rsaddawi !! nature.com/articles/s41467-0…
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Super excited to share our latest work with @MarcelaMaus , out this week in @Nature. We show that in vivo CRISPR screens can identify genes that enhance the efficacy of CAR T cell therapy. Brief explainer below! @MGBResearchNews @broadinstitute rdcu.be/eHZG4

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Obviously this is a super exciting and fast moving space with all the great work coming out this week. We're happy to be helping to advance our understanding of therapeutic T cell biology, and there will be more to come!
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Congrats to Nelson Knudsen, @escobar_giulia, @FpkMd, and the entire team for the publication of their amazing work! And thanks for @MGHCancerCenter and @broadinstitute for the support!
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