Thank you!

Link to Yale News article about this work: news.yale.edu/2025/10/02/n...

Such a pleasure collaborating with you and your lab too, Mandar! Cheers!

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

Link to paper: www.nature.com/articles/s41... 11/12

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

We expect that applying these approaches broadly will have an enormous impact on understanding the epigenetic basis of cancer in situ and will lead to the development of novel diagnostic, prognostic, and therapeutic biomarkers based on the 3D genome. 9/12

Our work also establishes a series of experimental and analytic methodologies (e.g., Trace2State, Trace2Biomarker, Trace2Regulator), allowing adaptation of these pipelines by the research community to study many other types of cancer and biological systems. 8/12

Overall, our work charts a comprehensive blueprint of 3D genome alterations during cancer progression in the native tissue context and systematically demonstrates how this rich resource can provide novel biological insights and potential biomarkers. 7/12

4) A new way to discover novel 3D genome regulatory genes in cancer, which can also serve as potential therapeutic targets. 6/12

3) A new 3D genome function, as our data reveal that cancer genes associated with 3D compartment changes are more stably regulated than non-compartment-regulated genes. 5/12

2) The utility of 3D genome mapping in better discovering prognostic and predictive biomarkers – uncovering novel candidate progression driver genes associated with patient survival as potential therapeutic targets. 4/12

1) Surprisingly nonmonotonic, stage-specific alterations in global 3D genome folding heterogeneity, compactness, and compartmentalization as cancers progress from normal to preinvasive to invasive tumors, elucidating an unexpected 3D genome structural bottleneck during early cancer progression. 3/12

Particularly, we further developed a single-cell, genome-wide chromatin tracing method for applications to lung, pancreas, and cancer tissues. We applied our method to faithful autochthonous murine models of lung and pancreatic cancers that mimic the cognate human cancers. Our data revealed: 2/12

Thank you @genometdcc.bsky.social and the National Human Genome Research Institute for inviting me to present this introductory lecture to the public at the Genomic Technologies Open Science Day 2025!

We expect Epi-PHR will find broad application in diverse biological and medical contexts. Link to our preprint: www.biorxiv.org/content/10.1... 8/8

Surprisingly, we found among the maternal copies of this locus, the relationship between the histone mark and a chromatin domain boundary is opposite to what one would expect. This surprising finding was uniquely enabled by Epi-PHR. 7/8