Epigenetics Podcast

In this episode of the Epigenetics Podcast, we talked with Peggy Farnham from the Keck School of Medicine at USC about her work on establishing the ChIP Method in mammalian cells.

In this episode, we dive into the relationship between transcription factors, chromatin dynamics, and gene expression with Professor Peggy Farnham from the Keck School of Medicine at USC. Professor Farnham shares her profound insights into how her groundbreaking research has reshaped our understanding of gene regulation and its implications in cancer. We explore how she has been a pioneer in mapping the genome-wide landscape of regulatory proteins, illuminating the molecular logic behind transcriptional control and its disruption in cancer biology.

The interview starts with her instrumental role in adapting chromatin immunoprecipitation (ChIP) technology from yeast to human cells. Professor Farnham reflects on the technical challenges she faced during this transition, such as the quest for visibility of signals in mammalian systems. Her ability to innovate and troubleshoot challenges led to significant advancements in techniques that allow for the rapid identification of transcription factor binding sites, fundamentally changing the landscape of epigenetic research.

As the discussion progresses, we learn about Professor Farnham's active involvement in the ENCODE project, where she contributed to high-resolution mapping of transcription factors and regulatory elements in human cells. She articulates her appreciation for collaborative efforts in science, highlighting how working within a consortium harnesses the collective expertise of diverse research groups. This collaboration not only bolstered the credibility of the data produced but also propelled the field forward in understanding the complexity of gene regulation.

Through her participation in various projects, such as the Psyc-ENCODE consortium and the Roadmap Epigenome Mapping Consortium, Professor Farnham shares insights into her investigation of epigenetic variations, particularly in relation to complex disorders like schizophrenia. Her findings underscore the nuances of enhancer variability among individuals and the implications for understanding disease mechanisms, thereby advancing our knowledge of genetic regulation and its contributions to diverse biological outcomes.

Moreover, the episode highlights Professor Farnham's reflective understanding of emerging technologies in the field. She discusses the evolution of methods that allow researchers to investigate gene regulation at single-cell resolution, recognizing the significant implications these innovations have for our comprehension of cellular differentiation and the transcriptional landscape.

References

Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ. Use of chromatin immunoprecipitation to clone novel E2F target promoters. Molecular and Cellular Biology. 2001 Oct;21(20):6820-6832. DOI: 10.1128/mcb.21.20.6820-6832.2001. PMID: 11564866; PMCID: PMC99859.

Wells J, Farnham PJ. Characterizing transcription factor binding sites using formaldehyde crosslinking and immunoprecipitation. Methods (San Diego, Calif.). 2002 Jan;26(1):48-56. DOI: 10.1016/s1046-2023(02)00007-5. PMID: 12054904.

Rhie SK, Schreiner S, Witt H, et al. Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation. Science Advances. 2018 Dec;4(12):eaav8550. DOI: 10.1126/sciadv.aav8550. PMID: 30555922; PMCID: PMC6292713.

Tak YG, Hung Y, Yao L, et al. Effects on the transcriptome upon deletion of a distal element cannot be predicted by the size of the H3K27Ac peak in human cells. Nucleic Acids Research. 2016 May;44(9):4123-4133. DOI: 10.1093/nar/gkv1530. PMID: 26743005; PMCID: PMC4872074.

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In this episode of the Epigenetics Podcast, we talked with Will Wang from Sanford Burnham Prebys about his work on muscle stem cell repair, regeneration, and aging, exploring spatial-omics and machine learning.

We begin our conversation by exploring the traditional concepts of spatial biology and how they have evolved to play a critical role in disease research. Dr. Wang recounts his journey from a young student in a family of academics to becoming a leading figure in regenerative biology, highlighting how his early interests in life sciences, natural problem-solving abilities, and inspirations from mentorship set the stage for his current research trajectory.

Throughout the discussion, we uncover key insights on how muscle stem cells transition from a quiescent state to a proliferative state in response to injury and how this dynamic process is governed by the epigenetic landscape and various signalling pathways. Dr. Wang emphasises the impact of external factors—be it microenvironment conditions or metabolic cues—on the fate and function of these stem cells, reflecting on the methodologies used to investigate these processes throughout his career.

He shares fascinating findings from his PhD work, where he explored the regulatory role of transcription factors like PAX-7 in muscle stem cell activation, and how subsequent research developed in his postdoc at Stanford further illuminated the relationship between metabolism and histone acetylation. This pivotal work not only demonstrated how metabolic states dictate epigenetic modifications but also offered potential therapeutic insights for muscle degeneration and repair.

As we move into more recent projects, Dr. Wang discusses the advances in multiplexed spatial proteomics and the insights garnered from a single-cell spatiotemporal atlas of muscle regeneration, which highlight the cellular heterogeneity in muscle tissue. He describes the use of novel computational tools, including neural networks, to uncover the regulatory mechanisms underlying stem cell function, particularly how prostaglandin signalling informs the regeneration process and how age impacts stem cell efficacy. The episode then wraps up with an engaging dialogue about the future implications of Dr. Wang’s work in addressing age-related muscle degradation and broader applications in regenerative medicine.

References

Yucel, N., Wang, Y. X., Mai, T., Porpiglia, E., Lund, P. J., Markov, G., Garcia, B. A., Bendall, S. C., Angelo, M., & Blau, H. M. (2019). Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function. Cell Reports, 27(13), 3939-3955.e6. https://doi.org/10.1016/j.celrep.2019.05.092

Wang, Y. X., Palla, A. R., Ho, A. T. V., Robinson, D. C. L., Ravichandran, M., Markov, G. J., Mai, T., Still, C., Balsubramani, A., Nair, S., Holbrook, C. A., Yang, A. V., Kraft, P. E., Su, S., Burns, D. M., Yucel, N. D., Qi, L. S., Kundaje, A., & Blau, H. M. (2025). Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength. Cell Stem Cell, 32(7), 1154-1169.e9. https://doi.org/10.1016/j.stem.2025.05.012

Related Episodes

Stem Cell Transcriptional Regulation in Naive vs. Primed Pluripotency (Christa Buecker)

The Effect of Mechanotransduction on Chromatin Structure and Transcription in Stem Cells (Sara Wickström)

Epigenetic Regulation of Stem Cell Self-Renewal and Differentiation (Peggy Goodell)

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Dr. Stefan Dillinger on LinkedIn

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Email: [email protected]

In this episode of the Epigenetics Podcast, we talked with Will Wang from Sanford Burnham Prebys about his work on muscle stem cell repair, regeneration, and aging, exploring spatial-omics and machine learning.

We begin our conversation by exploring the traditional concepts of spatial biology and how they have evolved to play a critical role in disease research. Dr. Wang recounts his journey from a young student in a family of academics to becoming a leading figure in regenerative biology, highlighting how his early interests in life sciences, natural problem-solving abilities, and inspirations from mentorship set the stage for his current research trajectory.

Throughout the discussion, we uncover key insights on how muscle stem cells transition from a quiescent state to a proliferative state in response to injury and how this dynamic process is governed by the epigenetic landscape and various signalling pathways. Dr. Wang emphasises the impact of external factors—be it microenvironment conditions or metabolic cues—on the fate and function of these stem cells, reflecting on the methodologies used to investigate these processes throughout his career.

He shares fascinating findings from his PhD work, where he explored the regulatory role of transcription factors like PAC-7 in muscle stem cell activation, and how subsequent research developed in his postdoc at Stanford further illuminated the relationship between metabolism and histone acetylation. This pivotal work not only demonstrated how metabolic states dictate epigenetic modifications but also offered potential therapeutic insights for muscle degeneration and repair.

As we move into more recent projects, Dr. Wang discusses the advances in multiplexed spatial proteomics and the insights garnered from a single-cell spatiotemporal atlas of muscle regeneration, which highlight the cellular heterogeneity in muscle tissue. He describes the use of novel computational tools, including neural networks, to uncover the regulatory mechanisms underlying stem cell function, particularly how prostaglandin signalling informs the regeneration process and how age impacts stem cell efficacy. The episode then wraps up with an engaging dialogue about the future implications of Dr. Wang’s work in addressing age-related muscle degradation and broader applications in regenerative medicine.

References

Yucel, N., Wang, Y. X., Mai, T., Porpiglia, E., Lund, P. J., Markov, G., Garcia, B. A., Bendall, S. C., Angelo, M., & Blau, H. M. (2019). Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function. Cell Reports, 27(13), 3939-3955.e6. https://doi.org/10.1016/j.celrep.2019.05.092

Wang, Y. X., Palla, A. R., Ho, A. T. V., Robinson, D. C. L., Ravichandran, M., Markov, G. J., Mai, T., Still, C., Balsubramani, A., Nair, S., Holbrook, C. A., Yang, A. V., Kraft, P. E., Su, S., Burns, D. M., Yucel, N. D., Qi, L. S., Kundaje, A., & Blau, H. M. (2025). Multiomic profiling reveals that prostaglandin E2 reverses aged muscle stem cell dysfunction, leading to increased regeneration and strength. Cell Stem Cell, 32(7), 1154-1169.e9. https://doi.org/10.1016/j.stem.2025.05.012

Related Episodes

Stem Cell Transcriptional Regulation in Naive vs. Primed Pluripotency (Christa Buecker)

The Effect of Mechanotransduction on Chromatin Structure and Transcription in Stem Cells (Sara Wickström)

Epigenetic Regulation of Stem Cell Self-Renewal and Differentiation (Peggy Goodell)

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Dr. Stefan Dillinger on LinkedIn

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In this episode of the Epigenetics Podcast, we talked with Mitch Guttman from Caltec about ChIP-DIP (ChIP-Done In Parallel).

ChIP-DIP is a newly developed approach for high-resolution protein–DNA interaction mapping. The method uses antibody-guided isolation of denaturant-insoluble protein–DNA complexes, resulting in substantially improved specificity and peak definition compared with conventional ChIP-seq. We explore why denaturation resistance is central to the workflow, how the method performs across transcription factors, chromatin regulators, and histone marks, and what experimental parameters determine its success. The conversation also covers current limitations, practical adoption details, and perspectives on how ChIP-DIP fits into the broader landscape of chromatin profiling technologies.

References

Perez, A. A., Goronzy, I. N., Blanco, M. R., Yeh, B. T., Guo, J. K., Lopes, C. S., Ettlin, O., Burr, A., & Guttman, M. (2024). ChIP-DIP maps binding of hundreds of proteins to DNA simultaneously and identifies diverse gene regulatory elements. Nature genetics, 56(12), 2827–2841. https://doi.org/10.1038/s41588-024-02000-5

Ramani, V. Split-pool barcoding serves up an epigenomic smorgasbord. Nat Genet 56, 2596–2597 (2024). https://doi.org/10.1038/s41588-024-01980-8

Related Episodes

Split-Pool Recognition of Interactions by Tag Extension (SPRITE) (Mitch Guttman)

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In this episode of the Epigenetics Podcast, we talked with Fides Zenk from the École polytechnique fédérale de Lausanne about her work on transgenerational inheritance in Drosophila and brain organoids for human development insights.

Dr. Zenk begins by sharing her journey into the field of biology, revealing her childhood fascination with nature and the intricate details of plant development. Her transition from an interest in ecology to a deep dive into molecular biology and gene regulation lays the groundwork for understanding her current research focus. We explore how her early experiences continue to shape her scientific curiosity, particularly her passion for studying cellular changes over time during embryonic development.

As the conversation progresses, Dr. Zenk paints a vivid picture of her work at EPFL, where she combines functional genomics, chromatin profiling, and molecular biology techniques. She elaborates on her initial research during her PhD with Nicola Iovino, where she investigated the transgenerational inheritance of histone modifications in Drosophila. This discussion includes fascinating insights into how histone modifications can carry information across generations and their implications in gene expression regulation during early embryonic stages.

Dr. Zenk also provides a glimpse into her postdoctoral work with Barbara Treutlein, where she shifted focus to human models and quantitative analysis using brain organoids. This segment of the episode reveals her commitment to translating molecular mechanisms to human health, especially in understanding the intricacies of brain development and neurogenesis. She describes how her team mapped dynamic changes in histone modifications during critical developmental stages, integrating various data modalities to build an intricate developmental atlas.

 

References

Zenk F, Loeser E, Schiavo R, et al. Germ line-inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition. Science (New York, N.Y.). 2017 Jul;357(6347):212-216. DOI: 10.1126/science.aam5339. PMID: 28706074.

Zenk F, Zhan Y, Kos P, et al. HP1 drives de novo 3D genome reorganization in early Drosophila embryos. Nature. 2021 May;593(7858):289-293. DOI: 10.1038/s41586-021-03460-z. PMID: 33854237; PMCID: PMC8116211.

Zenk F, Fleck JS, Jansen SMJ, et al. Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems. Nature Neuroscience. 2024 Jul;27(7):1376-1386. DOI: 10.1038/s41593-024-01652-0. PMID: 38914828; PMCID: PMC11239525.

Related Episodes

The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi)

Mapping the Epigenome: From Arabidopsis to the Human Brain (Joseph Ecker)

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Dr. Stefan Dillinger on LinkedIn

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Email: [email protected]