New research shared by Dan McQuaid
@muzumdarlab.bsky.social links #obesity-driven #pancreaticcancer to dysregulation of the hormone cholecystokinin (CCK). #AACR26
@theaacr.bsky.social @oncoalert.bsky.social

8/ This was a close collaboration with @krishnaswamylab.bsky.social @yalecbb.bsky.social with help from #KenLoh
#RichardKibbey @yalemed.bsky.social. Special thanks to @damonrunyon.org @lustgarten.org @yalecancer.bsky.social for critical funding support. #CancerBiology

7/Kudos to #CathyGarcia, #AarthiVenkat, #DanMcQuaid @yalecancer.bsky.social @yalecbb.bsky.social for leading the effort with critical contributions from #SherryAgabiti @rebeccastarble.bsky.social #AlexanderTong @christianfruiz.bsky.social #AkinSogunro #JeremyJacox

6/🔑Takeaways:
1️⃣β cells are essential PDAC drivers
2️⃣β cell stress biology links to tumorigenesis
3️⃣Obesity-driven PDAC is not just about insulin. It’s CCK-dependent.
4️⃣ Endocrine–exocrine CCK signaling is a PDAC driver and potential target for prevention

5/🔍Technical Innovations:
💻🐁🔬Integration of PDAC/obesity models with genetic perturbation of CCK and lineage tracing
📈scRNA-seq coupled with cutting-edge computational tools developed by @KrishnaswamyLab
⚔️In silico hypothesis generation with experimental validation in vivo

4/🔬Mechanism:
Obesity rewires β cell identity towards an immature, stress-adapted state in 🐁 and 🙋🏾‍♂️. Obesity →🔺ER stress →🔺JNK/cJun activation →🔺CCK expression → transcriptional alterations in islet-proximal exocrine acinar cells →🔺islet-proximal tumorigenesis

3/🧬Key Findings:
🔺β cell CCK promotes tumorigenesis in lean 🐁
🔺Pancreatic CCK knockout ablates obesity-driven PDAC progression
🔺 Pancreatic CCK expression, but not insulin, is positively associated with disease
🔺 Obesity increases islet-proximal tumor formation

2/💡New insight: Now, we show that β cell-derived CCK is necessary and sufficient for obesity-driven PDAC development, resulting in increased tumor formation near islets. What’s more? The effect is independent of insulin, challenging conventional wisdom on obesity and cancer.

1/ 📑 Background: Obesity increases #PancreaticCancer (PDAC) risk, but how? Previously, we found that obesity accelerates pancreatic tumorigenesis in 🐁 and induces the expression of the hormone CCK in β cells, whereas weight loss reverses these effects. t.co/ApKJjgMkKg

📢 New paper alert 🚨 We found that β cells are bona fide drivers of #obesity-associated #PancreaticCancer progression → targeting the #endocrine pancreas might prevent #exocrine cancer. 🔑 #CancerBiology. @yalecancer.bsky.social @yalemed.bsky.social🧵 👇🏾 www.nature.com/articles/s41...

Thanks to @lustgarten.org for its critical support of our research! @yalecancer.bsky.social

Researchers Identify Hormone Behind Obesity-Induced Pancreatic Cancer Yale scientists identified a hormone that initiates the development and progression of pancreatic cancer in obesity. And it’s not insulin.

Hormone behind obesity-induced #pancreaticcancer discovered: “We discovered the pancreas inappropriately produces the hormone #cholecystokinin in response to obesity and was a key driver of obesity-associated pancreatic cancer in mice.”-@muzumdarlab.bsky.social
medicine.yale.edu/cancer/news-...

Discovery that #obesity induces the expression of the peptide hormone cholecystokinin (CCK) in #β-cells, affecting the peri-islet acinar cells and promoting islet-proximal #tumor formation @muzumdarlab.bsky.social @krishnaswamylab.bsky.social doi.org/10.1038/s414...

Studies in mice define endocrine-exocrine beta cell-derived CCK signaling as a bona fide driver of #obesity associated PDAC development and uncover avenues to target the endocrine pancreas to subvert exocrine tumorigenesis. #pancreaticcancer www.nature.com/articles/s41...

We recently added a public track hub of "cancer effect size" across 20 TCGA cancer cohorts. Thank you to @jeffreytownsend.bsky.social and his lab at Yale University for providing the data. View it on the Genome Browser here: https://bit.ly/496Cx92

Read our @natgenet.nature.com News&Views on the impressive work by @muzumdarlab.bsky.social and @sstevenwang.bsky.social.

How does the 3D genome guide Kras-driven cancers evolution?

Find out with single-cell genome-wide chromatin tracing!

📖https://rdcu.be/eShAY

A career development grant from the AACR enabled Yale Cancer's Luisa Escobar-Hoyos, MSc, PhD, to secure two major multi-year federal grants for her pancreatic cancer research: Learn more in #AACRStories: www.aacr.org/about-the-aa... #PancreaticCancerAwarenessMonth

Congrats to the newly minted Dr. Ge @xiangyuge.bsky.social for defending her thesis today! A tour de force talk on her work unraveling signaling interactions between #PI3K and #KRAS. @yalecancer.bsky.social. Check out her preprint: www.biorxiv.org/content/10.1...

A new study led by Dr. Prasanna Ananth explores how the
21st Century Cures Act—giving patients immediate access to electronic health records, impacts #cancer care in the pediatric oncology population.
yalecancercenter.org/news-article...

Register now! www.eventbrite.com/e/the-sixth-...

Excited to present at the sixth annual #ConnectingTheDots symposium with @cityofhope.bsky.social. Join us Nov. 7 for a deep dive into the #diabetes-#cancer interface.

Tracing the evolution of single-cell 3D genomes in Kras-driven cancers - Nature Genetics This study uses chromatin tracing to identify alterations in single-cell 3D genome conformation during the progression of Kras-driven mouse lung adenocarcinoma and pancreatic ductal adenocarcinoma, an...

🎉PUBLISHED @natgenet.nature.com

📰Tracing the evolution of single-cell 3D genomes in Kras-driven #cancers.

By Miao Liu, @muzumdarlab.bsky.social, @sstevenwang.bsky.social and colleagues.

⬇️

www.nature.com/articles/s41...

7/ This was a close collaboration with @sstevenwang.bsky.social. Kudos to #MiaoLiu, #SherryAgabiti, and #ShengyanJin for leading the effort with critical collaboration from @christianfruiz.bsky.social @jeffreytownsend.bsky.social @yalecancer.bsky.social and funding from #NCI @theaacr.bsky.social

6/ 🚀 Take-home:
The first single-cell 3D genome atlas of cancer in situ. Stage-specific shifts + new gene regulators = a 3D genomics roadmap for potential biomarkers and targets for precision oncology.

5/ 🤖 The twist:
3D genome signatures don’t just classify tumor states—they add predictive & prognostic power beyond RNA-seq alone 📈.
Compartment changes flagged key genes, spotlighting Rnf2 as a novel regulator of cancer genome folding.

4/ 📊 The discovery:
3D genome changes are non-linear and exhibit convergent evolution across tumors. Tumors go through stage-specific shifts in compaction, compartment identity & heterogeneity—with a “structural bottleneck” early on. ⏳

3/ 🛠 The tech:
Using chromatin tracing, we imaged hundreds of loci across all 19 mouse autosomes in situ, mapping 3D genomic evolution in single #LungCancer and #PancreaticCancer cells within intact tissues. 📸

2/ 🔍 Why it matters:
Cancer isn’t just about mutations—it’s also how DNA folds in 3D. This study maps genome architecture from normal → pre-cancer → advanced cancer, at single-cell resolution.

Tracing the evolution of single-cell 3D genomes in Kras-driven cancers - Nature Genetics This study uses chromatin tracing to identify alterations in single-cell 3D genome conformation during the progression of Kras-driven mouse lung adenocarcinoma and pancreatic ductal adenocarcinoma, an...

1/ 🚨 New in Nature Genetics @naturegenet.bsky.social: 
“Tracing the evolution of single-cell 3D genomes in Kras-driven cancers” 🧬🧩
👉 The first atlas of how genome folding changes during cancer progression.
www.nature.com/articles/s41...

💡 Cancer cells don’t just mutate—they reorganize their DNA in 3D space.
Our new study shows how the genome’s folding pattern shifts as tumors progress, cell by cell 🧩🧬.
It’s the first 3D genome atlas of cancer progression.
Thread 👇