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Reposted by Rushika M. Perera

UCSF Helen Diller Family Comprehensive Cancer Center @ucsfcancer.bsky.social · Jun 4

Senior author @rushika-perera.bsky.social
@ucsanfrancisco.bsky.social on latest publication suggesting new opportunities to treat pancreatic cancer, which is notoriously resistant to many therapies | Pancreatic Cancer Spreads to Liver or Lung Thanks to This Protein cancer.ucsf.edu/news/2025/06...

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Rushika M. Perera @rushika-perera.bsky.social · May 22

Thanks Walter !

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Rushika M. Perera @rushika-perera.bsky.social · May 22

Thank you my friend😊

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Rushika M. Perera @rushika-perera.bsky.social · May 21

thank you! 😊

Rushika M. Perera @rushika-perera.bsky.social · May 21

thanks John!

Rushika M. Perera @rushika-perera.bsky.social · May 21

thank yoy!

Rushika M. Perera @rushika-perera.bsky.social · May 21

thanks Jim !

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Rushika M. Perera @rushika-perera.bsky.social · May 21

Thank you Christian! 🙏

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Rushika M. Perera @rushika-perera.bsky.social · May 21

Thanks Gina !

Rushika M. Perera @rushika-perera.bsky.social · May 21

We are grateful to the granting agencies, including
@theaacr.bsky.social, NIH, The Ed Mara Passion to Win Fund and the Belgian American Education Foundation (to G.R), which supported this work.

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Rushika M. Perera @rushika-perera.bsky.social · May 21

Thank you to our wonderful collaborators and their lab members - @robzonculab.bsky.social Jen Jen Yeh,
Eric Collisson, the German PDAC consortium, Mark Looney, Bruce Wang, Grace Kim, Kwun Wen - and to
@nature.com and the reviewers for their thoughtful review of our study.

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Rushika M. Perera @rushika-perera.bsky.social · May 21

These findings show that chol. uptake favors liver growth, while synthesis supports lung growth. Accordingly, PCSK9 o/e shifted liver-avid cells to the lung, while PCSK9 KO redirected lung-avid cells to the liver, establishing PCSK9 as a key regulator of metastatic organ choice

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Rushika M. Perera @rushika-perera.bsky.social · May 21

Reliance on de novo cholesterol synthesis, enables lung-avid cells to produce intermediates like 7-dehydrocholesterol that confer resistance to oxidative stress (eg, ferroptosis) in the oxygen-rich lung environment.

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Rushika M. Perera @rushika-perera.bsky.social · May 21

The ability to uptake cholesterol and route it to the lysosome, enables liver-avid cells to maintain high mTORC1 signaling and produce an oxysterol (eg, 24-hydroxycholesterol) that can activate adjacent hepatocytes to support tumor growth.

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Rushika M. Perera @rushika-perera.bsky.social · May 21

PCSK9 is a negative regulator of LDLR - the receptor for uptake of LDL-cholesterol. Accordingly, lung-avid lines which express high PCSK9 cannot uptake LDL and instead biosynthesize cholesterol, while liver-avid lines which express low PCSK9 efficiently uptake LDL-cholesterol.

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Rushika M. Perera @rushika-perera.bsky.social · May 21

To identify metabolic drivers linked to secondary organ choice, we interrogated gene expression analyses to determine which genes were differentially upregulated in lung- versus liver-avid lines. This analysis identified PCSK9 as the top ranked gene correlating with lung-avid

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Rushika M. Perera @rushika-perera.bsky.social · May 21

Gilles then validated these findings using in vivo transplant models of metastasis and showed that specific PDAC lines preferred to seed and grow in the liver while others preferred the lung. We also noted that metastatic organ preference correlates with PDAC subtype.

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Rushika M. Perera @rushika-perera.bsky.social · May 21

Our study began by interrogating the MetMap database depmap.org/metmap/ to identify organ tropic behaviors of human PDAC cell lines. We noted that several lines showed selective preference for liver colonization relative to other organs including the lung.

depmap.org

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Rushika M. Perera @rushika-perera.bsky.social · May 21

PDAC metastasizes to the liver, lungs, peritoneum and lymph nodes - we were interested in identifying key metabolic dependencies that enable efficient seeding the colonization in the liver and lungs.

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Rushika M. Perera @rushika-perera.bsky.social · May 21

Online today in @nature.com - our latest study led by superstar postdoc Gilles Rademaker detailing the role of PSCK9 in driving sterol dependent metastatic organ choice in pancreatic cancer nature.com/articles/s41...
full text available here 👉 rdcu.be/em0VG and thread 👇

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Reposted by Rushika M. Perera

Aria Vaishnavi, PhD @drariav.bsky.social · May 9

I am thrilled to share that the first preprint from my lab is now available on bioRxiV! In this study, our team elucidates the role of autocrine ligands in the aberrant behavior of oncogene-driven lung cancer.

www.biorxiv.org/content/10.1...

BRAFV600E-Driven Lung Tumorigenesis Requires Ligand-Mediated Activation of ERBB Receptor Signaling

Secretion of ligands of the human epidermal growth factor (EGFR) family of receptors or erythroblastic leukemia viral oncogene family (ERBB1-4) is a feature common to many cancer cells. However, our u...

www.biorxiv.org

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Reposted by Rushika M. Perera

UCSF Health @ucsfhealth.bsky.social · May 9

👏 Congratulations to Dr. Edward Chang on his election to the National Academy of Sciences! Dr. Chang is the first neurosurgeon to achieve this prestigious distinction since Harvey Cushing's election more than 100 years ago in 1917!
More about this historic recognition ➡️ ucsfh.org/438cefp

Dr. Edward Chang poses in a blazer and white button-down shirt.

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Reposted by Rushika M. Perera

Micha Rapé Lab @micharapelab.bsky.social · Apr 24

Wonderful talk by @rushika-perera.bsky.social of @ucsfhealth.bsky.social today in our @mti-ucb.bsky.social/#MolecularTherapeutics seminar series at @ucberkeleyofficial.bsky.social today, presenting cool data about organ-selective metastasis! Thank you!!!

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Reposted by Rushika M. Perera

Aakriti Jain @aakritijain.bsky.social · Mar 27

SO excited to share that a major part of the postdoctoral work in @robzonculab.bsky.social lab is now published: “Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins” www.science.org/doi/10.1126/...

Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...

www.science.org

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Rushika M. Perera @rushika-perera.bsky.social · Mar 28

An incredible tour de force in biochemistry and cell biology by superstar @robzonculab.bsky.social lab postdoc @aakritijain.bsky.social
LyLAP - a new lysosomal protease responsible for degrading integral membrane proteins in highly phagocytic cells like #PDAC cells.
www.science.org/doi/10.1126/...

Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins

Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...

www.science.org

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