In this episode of the Epigenetics Podcast, we talked with Kunal Rai from MD Anderson Cancer Center about his work on chromatin state reprogramming in cancer progression.

A major part of the conversation covers his postdoctoral work on active DNA demethylation. He describes how he identified an AID-MBD4-based mechanism, later supported by GAD45, and how this work showed a role for DNA demethylation in early neuronal differentiation and in colon cancer initiation.

We then discuss his move into his own lab and his work on melanoma progression. He explains how he used broad epigenomic profiling, chromatin state analysis, and 3D chromatin methods to study enhancers and chromatin organization, and how these approaches helped reveal changes linked to cancer progression.

Another topic is his work on epigenetic regulators such as RNF2 and KMT2D. He describes findings on polycomb and trithorax-related factors, including tumor-suppressive roles for KMT2D in melanoma and lung cancer, and how KMT2D loss affects cell phenotype and metabolism.

Finally, we talk about lab organization, collaboration, and newer technologies. He says his group works across multiple cancer types and increasingly includes immunology, single-cell methods, spatial epigenomics, and clinical translation, while still using ChIP-seq, CUT&RUN, and CUT&Tag where appropriate.

• Fiziev, P., Akdemir, K. C., Miller, J. P., Keung, E. Z., Samant, N. S., Sharma, S., Natale, C. A., Terranova, C. J., Maitituoheti, M., Amin, S. B., Martinez-Ledesma, E., Dhamdhere, M., Axelrad, J. B., Shah, A., Cheng, C. S., Mahadeshwar, H., Seth, S., Barton, M. C., Protopopov, A., Tsai, K. Y., … Rai, K. (2017). Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression. Cell reports, 19(4), 875–889. https://doi.org/10.1016/j.celrep.2017.03.078
• Terranova, C. J., Tang, M., Maitituoheti, M., Raman, A. T., Ghosh, A. K., Schulz, J., Amin, S. B., Orouji, E., Tomczak, K., Sarkar, S., Oba, J., Creasy, C., Wu, C. J., Khan, S., Lazcano, R., Wani, K., Singh, A., Barrodia, P., Zhao, D., Chen, K., … Rai, K. (2021). Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy. Cell reports, 36(3), 109410. https://doi.org/10.1016/j.celrep.2021.109410

• Epigenetic Signatures During Aging and Cancer (Alena van Bömmel)
• Epigenetic Mechanisms in Breast Cancer (Luca Magnani)
• The Effect of Histone Demethylases on Gene Expression and Cancer Cell Stability (Johnathan Whetstine)

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In this episode of the Epigenetics Podcast, we talked with Steffen Rulands from the Ludwig Maximilian University of Munich about how methods from statistical physics can be used to study collective phenomena in biology. We discuss his path from physics into stem cell biology and epigenetics, and how this background shapes the questions he asks in his work.

We talk about his lab’s focus on quantitative and mechanistic modeling rather than wet lab experiments. He explains that he uses single-cell genomics and other datasets to understand how cells make decisions, with interests ranging from development and regeneration to aging and rejuvenation.

A major topic is DNA methylation during embryonic development. We discuss how he and his collaborators found surprisingly simple, self-similar patterns in methylation over time and along the genome, and how they explained these patterns with a feedback loop between chromatin conformation and methylation deposition.

We also cover his collaboration on social insect colonies, where he examines how DNA methylation and gene regulation help explain stable social roles and flexibility when the queen is removed. In that system, interactions across the whole nest shape the regulation of queen- and worker-associated genes.

Later in the conversation, we turn to aging. We discuss his recent work on temporal hierarchies in epigenetic aging and on collective dynamics of DNA methylation, where we ask how molecular-scale events can combine to produce the long timescale of organismal aging. We close by talking about rejuvenation, general principles in aging, and the role of physics in identifying what is generic versus what is specifically regulated in biology.

• Rulands, S., Lee, H. J., Clark, S. J., Angermueller, C., Smallwood, S. A., Krueger, F., Mohammed, H., Dean, W., Nichols, J., Rugg-Gunn, P., Kelsey, G., Stegle, O., Simons, B. D., & Reik, W. (2018). Genome-Scale Oscillations in DNA Methylation during Exit from Pluripotency. Cell systems, 7(1), 63–76.e12. https://doi.org/10.1016/j.cels.2018.06.012
• Olmeda, F., Lohoff, T., Kafetzopoulos, I. et al. Scaling and self-similarity in the formation of the embryonic epigenome. Nat. Phys. 22, 931–940 (2026). https://doi.org/10.1038/s41567-026-03263-x

• Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)
• The Interplay of Nutrition, Metabolic Pathways, and Epigenetic Regulation (Ferdinand von Meyenn)
• Epigenetic Reprogramming During Mammalian Development (Wolf Reik)

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In this episode, we speak with Andrea Brand, Chair of the Department of Cell Biology at NYU Grossman School of Medicine and Director of the Regenerative Medicine Institute. We discuss her scientific path from yeast gene regulation to Drosophila neurobiology, and how early interests in DNA and microscopy shaped her career.

We talk about the development of the GAL4 system with Norbert Perrimon and how it enabled targeted gene expression in specific tissues and cells. Andrea explains why this approach has remained useful across decades, including its applications in Drosophila and beyond, while noting that no experimental system is perfect and results should be cross-checked with other methods.

We also discuss targeted DAM-ID and chromatin DAM-ID, methods developed in her lab to study protein-DNA interactions and chromatin marks in vivo without removing cells from their normal tissue environment. Andrea describes how these tools helped her lab analyze neural stem cells in their niche and investigate changes in chromatin during quiescence and reactivation.

A major theme of the conversation is neural stem cell quiescence. We cover how her lab found that quiescent stem cells can show unexpectedly open chromatin, express neuronal genes, and adopt neuron-like features, including long projections and interactions with neurons. We also discuss the link to metabolism, including feeding signals, the fat body, blood-brain barrier glia, insulin-like peptides, and TGF-beta signaling.

Finally, we talk about Andrea’s recent move toward human brain organoids and the goal of connecting model organism work to human biology and patient data. We discuss ongoing work on quiescent cells, TRIB family genes, and cancer–neuron interactions, as well as the need to better distinguish quiescence from senescence in vivo.

• Brand, A. H., & Perrimon, N. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development (Cambridge, England), 118(2), 401–415. https://doi.org/10.1242/dev.118.2.401
• Southall, T. D., Gold, K. S., Egger, B., Davidson, C. M., Caygill, E. E., Marshall, O. J., & Brand, A. H. (2013). Cell-type-specific profiling of gene expression and chromatin binding without cell isolation: assaying RNA Pol II occupancy in neural stem cells. Developmental cell, 26(1), 101–112. https://doi.org/10.1016/j.devcel.2013.05.020
• Tang, J. L. Y., Hakes, A. E., Krautz, R., Suzuki, T., Contreras, E. G., Fox, P. M., & Brand, A. H. (2022). NanoDam identifies Homeobrain (ARX) and Scarecrow (NKX2.1) as conserved temporal factors in the Drosophila central brain and visual system. Developmental cell, 57(9), 1193–1207.e7. https://doi.org/10.1016/j.devcel.2022.04.008
• Cheetham, S. W., & Brand, A. H. (2018). RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites. Nature structural & molecular biology, 25(1), 109–114. https://doi.org/10.1038/s41594-017-0006-4
• Cheetham, S. W., Gruhn, W. H., van den Ameele, J., Krautz, R., Southall, T. D., Kobayashi, T., Surani, M. A., & Brand, A. H. (2018). Targeted DamID reveals differential binding of mammalian pluripotency factors. Development (Cambridge, England), 145(20), dev170209. https://doi.org/10.1242/dev.170209

• scDamID, EpiDamID and Lamina Associated Domains (Jop Kind)
• Characterizing Chromatin at the Nuclear Lamina (Bas van Steensel)

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