Muzumdar Lab

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 👇

New paper on the role of H3K4me3 at enhancers! We (led by Haoming Yu) used dCas9 epigenome editing to add H3K4me3 to intergenic enhancers. This was (1) sufficient to turn up transcription at open, active regions and (2) has no effect on target gene transcription. genesdev.cshlp.org/content/earl...

Cancer's Progress Detailed by 3D Genomic Maps Using new technology, Yale researchers examine cancer progression in single cells to visualize and understand its evolution from pre-cancerous to advanced

New @natgenet.nature.com study from @muzumdarlab.bsky.social + @sstevenwang.bsky.social
maps 3D genomes in KRAS-driven lung & pancreatic #cancer, revealing stage-specific changes + potential biomarkers.

➡️ yalecancercenter.org/news-article...

Wonderful to collaborate with you and the team on this study, Steven!

This work was done in collaboration with my @yaleschoolofmed.bsky.social colleague Professor Mandar Muzumdar @muzumdarlab.bsky.social and co-led by Drs. Miao Liu, Shengyan Jin, and Sherry Agabiti. Congrats to all authors! Also thank you National Cancer Institute for funding this work! 10/12

Cancer's Progress Detailed by 3D Genomic Maps Using new technology, Yale researchers examine cancer progression in single cells to visualize and understand its evolution from pre-cancerous to advanced

Link to YSM News article about this work: medicine.yale.edu/news-article... 12/12

Glad to share our latest publication in Nature Genetics: Tracing the evolution of single-cell 3D genomes in Kras-driven cancers. In this work, we generated the first single-cell 3D genome atlases of any cancer using any technique. 1/12

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...

Excited to share our latest paper in @natgenet.nature.com with #SiyuanWang @yale.edu on the evolution of 3D genome organization in 🐁 models of #LungCancer and #PancreaticCancer. Kudos to #MiaoLiu #SherrySu! @yalecancer.bsky.social www.nature.com/articles/s41...

Systemic administration of an RNA binding and cell-penetrating antibody targets therapeutic RNA to multiple mouse models of cancer A cell-penetrating and RNA binding antibody forms noncovalent complexes with an immunogenic RNA to target tumors and achieve antitumor efficacy.

🎉 So proud of my wife
Natasha Pinto Medici on her latest co–first author paper in @ScienceTransMed!
🚀 Her team introduces TMAB3 — a tumor-targeted, RNA-binding antibody that delivers RNA directly into tumors after systemic injection.
www.science.org/doi/10.1126/...

Stellar flash talk and poster presentation on #ubiquitination regulators in #KRAS inhibitor resistance by our own #CassieMarkham @faseborg.bsky.social Protein Phosphorylation! @yalecancer.bsky.social

Phosphoinositide 3-kinase regulates wild-type RAS signaling to confer resistance to KRAS inhibition Despite the availability of RAS inhibitors and the dependence of >90% of pancreatic ductal adenocarcinomas (PDAC) on oncogenic KRAS mutations, resistance to KRAS inhibition remains a serious obstacle....

Way to go, @xiangyuge.bsky.social, for a fantastic talk on how #PI3K governs resistance to #KRAS inhibition in #PancreaticCancer cells @faseborg.bsky.social Protein Phosphorylation! @yalepathology.bsky.social @yalecancer.bsky.social. Check out her preprint: www.biorxiv.org/content/10.1...

8/👏 Kudos to lead author @xiangyuge.bsky.social with key contributions from Jaffar, Wenxue, Cassie, @christianfruiz.bsky.social, @moitrayee-lab.bsky.social, and Yansheng. #YCBI #YaleGenetics #YalePharm @yalecancer.bsky.social @lustgarten.org

Phosphoinositide 3-kinase regulates wild-type RAS signaling to confer resistance to KRAS inhibition Despite the availability of RAS inhibitors and the dependence of >90% of pancreatic ductal adenocarcinomas (PDAC) on oncogenic KRAS mutations, resistance to KRAS inhibition remains a serious obstacle....

7/ 🧠 Big picture:
Our findings reveal that #PI3K can act upstream of wild-type RAS to mediate resistance to #KRAS inhibition.
This refines our understanding of #RAS pathway plasticity and provides new insights into #DrugResistance mechanisms.
Read more: www.biorxiv.org/content/10.1...

6/ 💡 Therapeutic insight:
Co-inhibition of PI3K + KRAS abrogates bypass and kills resistant cells.
This gives a mechanistic rationale for dual targeting in KRAS-driven cancers.